Amgen Inc. (AMGN) Amgen Meeting on Rare Disease (Transcript)

Amgen Inc. (NASDAQ:AMGN) Amgen Meeting on Rare Disease February 22, 2024 4:00 PM ET

Company Participants

Justin Claeys – Vice President of Investor Relations

Murdo Gordon – EVP, Global Commercial Operations

Vikram Karnani – Executive, Rare Disease Business

Paul Burton – Chief Medical Officer

James Bradner – Chief Scientific Officer

Conference Call Participants

Jay Olson – Oppenheimer

Michael Yee – Jefferies

Yaron Werber – TD Cowen

Conor Mackay – Capital Markets

Robyn Karnauskas – Truist Securities

Chris Schott – JPMorgan

Operator

My name is Julian, and I’ll be your conference facilitator today for Amgen’s Rare Disease Investor Analyst Call. All lines have been placed on mute to prevent any background noise. There will be a question-and-answer session at the conclusion of the last speaker’s prepared remarks. In order to ensure that everyone has a chance to participate, we would like to request that you limit yourself asking one question during the Q&A session [Operator Instructions]

I would now like to introduce Justin Claeys, Vice President of Investor Relations. Mr. Claeys, you may now begin.

Justin Claeys

Thank you, Julian. Good afternoon, and welcome to our rare disease investor call. Rare disease is Amgen’s fourth and newest pillar of long-term growth and is additive to our opportunities in general medicine, oncology and inflammation. Today, you will hear from Murdo Gordon, Vikram Karnani, Paul Burton and Jay Bradner, who will provide a review of the strategic fit of rare disease with Amgen’s capabilities, the growth prospects for key in line products that are early in their lifecycle and the innovative pipeline of mid- and late stage opportunities.

Through the course of the discussion today, we will make some forward-looking statements, which are qualified by our Safe Harbor statement, and please note that actual results can vary materially. We will be reviewing slides during the call, which will be made available on our website after the call is completed.

Let me now turn the call over to Murdo.

Murdo Gordon

Thanks, Justin. At Amgen, our business is structured across four pillars: general medicine, oncology, inflammation and our newest addition, rare disease. Our strategic focus on rare disease began with the acquisition of TAVNEOS for patients with ANCA-associated vasculitis. The acquisition of Horizon has a young, fast growing portfolio of products, enhancing our ability to serve patients with rare diseases around the world, effectively establishing a strong additional pillar of growth for Amgen.

Looking ahead, we anticipate sustained growth across all of our pillars through the end of the decade and beyond. This growth will be driven by a combination of our established marketed products and the innovative pipeline projects currently underway across all four pillars. One significant event on our calendar is Rare Disease Day on February 29. This day serves as an important opportunity for Amgen employees globally to engage in activities supporting the rare disease patient community.

Through our Rare Is initiative, we will provide resources and programs benefiting all individuals living with rare diseases, further underscoring our commitment to making a positive impact in these patients’ lives.

Consistent with Amgen’s strategy of pursuing first-in-class or best-in-class innovative molecules, we’re committed to delivering highly differentiated therapies that address unmet medical needs. Our focus remains on pushing the boundaries of scientific discovery to develop groundbreaking treatments.

We’re leveraging our strong commercial and medical leadership in inflammation and nephrology along with our global scale to successfully launch and expand our rare disease products in key markets. By leveraging our expertise and resources, we aim to maximize the impact of these therapies and improve patient outcomes worldwide.

Furthermore, Amgen’s robust research and development capabilities coupled with our biologics manufacturing expertise uniquely position us to accelerate and add significant value to our rare disease portfolio. We’re dedicated to advancing the development and production of these life changing treatments.

Our combined cash flow provides us with the financial stability to sustain investments in innovation while also delivering value to our shareholders through a growing dividend. We remain committed to driving long-term shareholder value while also prioritizing investment in cutting-edge research and development initiatives.

Looking ahead, we anticipate that our strategic focus on rare disease will accelerate revenue growth and contribute to the accretion of non-GAAP earnings starting from 2024. We are confident that our innovative portfolio and strong financial foundation will enable us to continue making meaningful contributions to healthcare and delivering value to our shareholders.

Our rare disease business unit is built upon a foundation of innovation anchored by four medicines that are early in their lifecycle. TEPEZZA, the first and only treatment for thyroid eye disease, addressing a critical unmet need in this patient population. KRYSTEXXA, a groundbreaking therapy for uncontrolled gout offering a unique solution for patients struggling with this debilitating condition. UPLIZNA, the fastest growing biologic in neuromyelitis optica spectrum disorder, demonstrating remarkable efficacy and patient benefit. TAVNEOS, the only complement inhibitor designed specifically for ANCA-associated vasculitis, representing a significant advancement in the treatment landscape for this condition as well as other ultra-rare diseases.

In addition to these four key medicines, we’re proud to offer a portfolio of ultra-rare disease medicines, including RAVICTI, PROCYSBI, ACTIMMUNE. These treatments address life-threatening diseases, reflecting our commitment to providing innovative solutions for patients facing the most challenging health conditions. All of these medicines represent the forefront of medical innovation offering hope and improved quality of life for patients facing rare and often overlooked conditions.

As we continue to advance our rare disease business, we’re committed to expanding access and driving growth through our marketed products in the U.S. and internationally, while developing our pipeline to continue to deliver value to patients and shareholders alike.

It’s imperative to recognize why rare diseases necessitate a different approach. There are a few key data points that underscore this need. The majority of rare diseases remain untreated with only 5% of the estimated 10,000 rare diseases having available treatments. This highlights significant unmet medical need within this patient population. Rare diseases typically impact fewer than 200,000 individuals in the U.S., while ultra-rare diseases affect just a few thousand people. And the limited patient pool presents challenges in terms of patient identification, diagnosis, recruitment and in conducting clinical trials.

Low disease awareness, there’s often low awareness surrounding these rare diseases, which makes it really challenging to identify and diagnose affected individuals. And this lack of awareness contributes to delayed diagnosis and treatment initiation, and Vikram will talk more specifically about the patient journey for TEPEZZA in this call.

Patient challenges with rare disease, they face numerous difficulty including misdiagnosis, delays in diagnosis, a protracted journey to receiving the proper care, limited treatment options can further compound the difficulties faced by patients and their families.

Access to specialized care and treatment options is often limited by geographic barriers, particularly in rural or underserved areas. Patients can encounter challenges in accessing healthcare facilities equipped to manage their rare disease.

The pre-approval process for treatments can be burdensome, leading to delays and denials in insurance coverage and this can significantly impede patients’ access to life saving therapies. And advocacy communities play a crucial role in raising awareness and supporting patients with rare disease.

Their resources and reach can be limited, which further underscores the need for comprehensive support networks. Patients with rare disease require dedicated support throughout the duration of their therapy, not just at the onset. This includes access to specialized healthcare professionals, ongoing education, psychosocial support to navigate the challenges associated with their condition.

In light of these factors, it’s evident that addressing the unique needs of patients with rare disease demands a tailored and multifaceted approach. As a company, we are committed to advancing innovative treatments, enhancing disease awareness, providing comprehensive support to improve outcomes and quality of life for individuals affected by rare disease.

So the products within our rare disease pillar have delivered strong growth on a combined basis for the past several years, accounting for almost $4 billion in 2023. Importantly, these sales are almost entirely in the U.S., so contributions from international expansion will be additive. We still see significant opportunity within the U.S. given that there is relatively low penetration for each of these products. And as you will hear from Vikram and Paul, we have a portfolio of innovative products that address serious illness and are early in their lifecycle and so we see a number of ways to drive growth.

I’d like to turn it over now to Vikram, who will walk you through more detail on the rare disease portfolio.

Vikram Karnani

Thanks, Murdo. While each patient’s experience is unique, individuals with rare diseases tend to report commonalities such as a long road to diagnosis, limited treatment options and a need for research to better understand their medical condition. As you can see on the slide here, this journey is highly complex and on average, it can take nearly five years and more than seven specialists for a rare disease patient to get an accurate diagnosis. This diagnostic journey is not only exhausting for patients and their family members, but also burdensome. But a diagnosis is just the beginning. The barriers to access are significant as well.

These patients must jump through numerous access hurdles that require a different approach than what you see in large disease states. We have invested significant resources and developed industry-leading capabilities to help guide patients and their caregivers as they navigate this complex journey, providing them with individualized support and driving key payer policy decisions that will position these patients for success in getting the treatment that they need.

Being a rare disease patient often comes with a feeling of isolation and loneliness. Fostering a sense of community for these patients and their families is also an important part of our efforts through patient advocacy. As Murdo just alluded to, these organizations are another critical component of the rare disease patient experience, helping shorten the time to treatment and ensure that patients can access the medicines that they need. By providing vital education and resources, patient advocacy helps rare disease patients gain confidence and community throughout their journey.

This highly individualized intentional approach has positioned our rare disease portfolio for success in our mission to serve more rare disease patients. It’s because of this that we were ranked number one in overall corporate reputation among rare disease groups globally, as well as number one in overall corporate reputation amongst U.S. patient advocacy groups in 2023. We have consistently been at the top of this ranking for the past several years and are proud of the work we’ve done to support these rare disease communities.

At this point, I’m going to hand it over to Paul Burton, our Chief Medical Officer, to kick us off with TEZSPIRE for thyroid eye disease. Paul?

Paul Burton

Thank you, Vikram, and good afternoon, everybody. Thyroid eye disease or TED is an autoimmune disease in which the eye muscles and fatty tissue behind the eye becomes inflamed. We’re going to talk a lot today about inflammation, the acute damage that can harm causing cell proliferation, cell and tissue death and destruction, followed by the body’s natural response to that, which is fibrosis.

TED is primarily associated with an overactive thyroid gland due to Graves’ disease. Although it can rarely occur in patients with an underactive or even normally functioning thyroid gland as well. The inflammation that occurs in TED patients pushes the eyes forward so that they become bulging, and this is referred to as proptosis. It can also cause the eyes and eyelids to become red and swollen. In some individuals, the inflammation may involve the eye muscles causing the eyes to become out of alignment, leading to double vision or diplopia.

In rare cases, TED can cause blindness from pressure on the optic nerve at the back of the eye and ulcers that can form on the front of the eye on the cornea. TED was once thought to comprise two distinct phases of active inflammatory symptoms followed by chronic stable symptoms, but the same underlying disease pathophysiology likely drives TED throughout the entire course of the disease. Thyroid eye disease is assessed using the clinical activity score, which covers a number of different signs and symptoms, spanning pain, redness, swelling, and function. And we now refer to TED in terms of high and low clinical activity score of high and low TED.

In the next slide, I want to turn now to TEPEZZA, the first and only FDA approved treatment for thyroid eye disease, and I want to talk about its mechanism of action. Orbital Fibroblasts, a key driver of the pathophysiology of TED. Interactions between T cells and fibroblasts activate the inflammatory response and lead to the expansion of orbital soft tissue, muscle, as well as fat cells behind the eye.

The insulin-like growth factor 1 receptor or IGF-1R is one of the main autoantigens in TED, and this is over expressed in orbital fibroblasts in patients with TED. The IGF-1R and the thyroid stimulating hormone receptor are colocalized on orbital fibroblasts. Impept autoantibodies activate this IGF-1R TSH receptor signaling complex. And in doing that, it trigger release of pro inflammatory cytokines, infiltration of immune cells, overexpression of extracellular matrix glycosaminoglycans and fibroblast proliferation and differentiation.

TEPEZZA is designed to target and block the IGF-1 receptor, a key driver of TED pathophysiology throughout the course of the disease. That’s a key point, and I want to emphasize it. TEPEZZA is able to block the primary pathophysiological drive throughout the entire course of both high and low CAS thyroid eye disease.

By inhibiting IGF-1R, TEPEZZA prevents muscle and tissue expansion behind the eye to help reduce TED symptoms, improving proptosis, diplopia, and the inflammatory effects in TED patients.

In the next slide, I’m showing you now the clinical effectiveness of TEPEZZA. The results from a Phase 3 study assessing TEPEZZA in TED patients with a high clinical activity score or high CAS are shown on the left panel. In this study, the proptosis response, which was defined as a greater than or equal to 2-millimeter reduction in bulging or proptosis from baseline in the study eye without deterioration in the fellow eye was the primary endpoint. At week 24, a highly significant treatment effect was observed. 83% of patients treated with TEPEZZA had a reduction in proptosis compared with 10% of those people treated with placebo. Proptosis reduction was observed as early as six weeks with TEPEZZA in this study.

In our Phase 4 study in patients with low clinical activity score, seen in the figure on the right. Improvement of proptosis as measured by mean change from baseline was also observed as early as 12 weeks and continued to improve through 24 weeks of treatment. The majority of patients, in this case 62% of those treated with TEPEZZA, had clinically meaningful proptosis reduction compared to only 25% of patients in the placebo group by week 24. It’s important to note that in practice, patients with high clinical activity scores are primarily seen by ocular specialists, whereas those with lower clinical activity scores are primarily seen by ophthalmologists and endocrinologists.

I’ll now hand over again to Vikram to take us through thoughts on the patient population that can benefit from TEPEZZA.

Vikram Karnani

As you just heard from Paul, TED patients can experience a wide range of symptoms and the Phase 4 data demonstrated TEPEZZA’s effectiveness for both patient segments. With this updated indication and the emphasis on low activity, longer duration TED patients, we see an opportunity to substantially grow the U.S. TED market. For the approximately 100,000 patients with moderate to severe disease in the U.S. who could benefit from TEPEZZA, the majority of these patients are in low clinical activity score or low CAS settings. However, low CAS patients can still have significant quality of life impact from living with TED. They can be limited in their ability to perform daily tasks such as drive, use screens and interact with their families and friends.

As you can see from the symptoms that Paul shared earlier, TED presents a significant burden for those living with this serious condition. But interestingly, we found that physicians generally underestimate the quality of life impact that this disease can have.

We also know, however, that when quality of life is a factor, physicians are more than twice as likely to treat or refer patients. Therefore, this is one of our key focus areas going forward to help educate physicians on quality of life and TED patients, especially as it relates to low CAS patients whose visible symptoms may seem less severe.

Today, across the TEPEZZA appropriate population, penetration for TEPEZZA is in the high single-digits. So there still remains significant opportunity to treat more patients in both the high and low CAS settings. Over the last six months, since our Phase 4 data with low cast patients was first published, we have made progress in reaching low CAS patients and are continuing to drive updates here as we broaden our prescriber base and secure reimbursement.

With these positive leading indicators and high unmet need, on the next slide, we see a long-term growth opportunity for TEPEZZA in the U.S. Though we also recognize there is some time lag between our execution efforts and the realization of increased patient numbers. Significant growth opportunities still exist to grow in the high CAS patient segment and now our new Phase 4 data enables us to unlock even more patients who have lower activity, but still suffer a substantial impact to their quality of life.

Our focus in 2024 is to accelerate our efforts to educate key stakeholders on the importance of this new data and the updated indication, so we can reach more TED patients building on the foundation laid in 2023. To do this, we are expanding our reach and penetration with new prescribers focusing on comprehensive ophthalmologists and endocrinologists. We have already seen success with unique riders in these expanded specialties growing by more than 30% year-over-year.

As I mentioned earlier in talking about the rare disease patient journey, access barriers are one of the biggest challenges that patients face and a key part of that is medical policies. With the Phase 4 data, we have been able to generate favorable medical policy changes for greater than 50% of U.S. covered lives, and we expect to continue this momentum throughout 2024. That said, because of these policies and how they influence the prescription to infusion process, we generally see a seasonal decline in Q1 as compared to Q4 for our infused medicines as patients experience co pay and deductible resets and other changes in their health care coverage. You heard from Peter on our Q4 earnings call that there is a similar dynamic across Amgen’s portfolio, which is also primarily biologics, with the first quarter product sales expected to be the lowest quarter as a percentage of the full year.

For TEPEZZA in Q1 2024, we expect mid-single-digit year-over-year growth as compared to Q1 2023. We are also progressing TEPEZZA subcutaneous administration to drive increased adoption and improve the patient experience and plan to initiate a Phase 3 study in TED this year.

Shifting focus to the international expansion side of things. International expansion is a key area where TEPEZZA represents a meaningful long-term growth opportunity. This has been accelerated by our joining forces with Amgen as we tap into the organization’s robust global footprint and capabilities. Our expansion into both Japan and Europe is a high priority with regulatory review underway in Japan and filings in the EU throughout the year.

We were very pleased that TEPEZZA received orphan drug designation in Japan in December ’23, and we have since filed for high CAS approval in January this year. We expect to officially launch in Japan in early 2025. This is an important milestone because Japan represents a significant market for TED patients with nearly a 50-50 split of high CAS and low CAS patients.

To meet the needs of both patient segments in Japan, we also have a Phase 3 study currently underway to study this disease and its effectiveness with low CAS patients in the country. For Europe, we anticipate filings in the first half of this year and expect to launch following our launch in Japan.

This is another strong market opportunity with nearly one-third high CAS patients and roughly two-third low CAS patients, respectively. All of this will build on the solid foundation from our first international approval that came from Brazil last year and we are now progressing towards approval in additional countries, including in the Middle East.

Moving on to subcutaneous development. We also see an opportunity to increase adoption and improve the patient experience with our subcu development program. This is currently in development with a Phase 3 global study and we expect to enroll the first patient imminently. We believe this is a large opportunity to provide patients with an alternative option to our current IV formulation. And this highlights yet another area where we are seeing the benefits of our newly combined organization, giving us a chance to tap into Amgen’s industry-leading expertise with biologics, manufacturing and development to advance this effort.

With all of this in mind, we remain highly confident in the trajectory of this medicine. TEPEZZA still has a significant long-term growth potential given the current penetration in both the high CAS and low CAS patient segments. We have also gained valuable experience in the past four years since launch that has enabled us to refine our patient support model, helping us engage patients along the full continuum of care. This is critical to ensuring that these rare disease patients start and complete therapy on time.

From an international perspective, the integration with Amgen accelerated these efforts putting us that much closer to reaching key markets in Japan and Europe as well as fully realizing the potential of our existing markets like Brazil. We are also continuing to potentially improve the patient experience and increase adoption of TEPEZZA with the subcutaneous development program I just mentioned that is currently underway, and we look forward to the potential benefit that could bring to patients around the world.

Now, I’m going to hand it back to Paul to share a bit about KRYSTEXXA for uncontrolled gout.

Paul Burton

Great. Thanks, Vikram. Gout is the most common inflammatory arthritis. Uncontrolled gout is a systemic disease that is unresponsive to conventional therapies, and it can affect not only bones and joints but many other organ systems as well. Gout is associated with multiple comorbidities, including chronic kidney disease and hypertension.

The cardinal signs and symptoms of gout come from the buildup of uric acid crystals in many areas of the body. Clinical characteristics include elevated serum uric acid levels, acute gout flares and the deposition of uric acid crystals in tissues in the form of tophi. These signs and symptoms of gout due to the deposition of monosodium uric crystals in joints are described by patients as one of the most debilitating and painful experiences they can imagine. And you can understand how it must be to try and move a joint filled with razor-sharp urate crystals.

As noted earlier, the hyperuricemia accompanying gout is also a driver of cardiovascular disease, including hypertension, poriferal arterial disease, heart failure and stroke. In the next slide, we’ll look at the management of gout.

The management of gout has depended in the past on the use of disease-modifying agents, such as non-steroid or anti-inflammatory drugs and glucocorticoids. KRYSTEXXA, which is pegylated uricase, acts by converting insoluble uric acid into soluble allantoin, and this can then be rapidly and easily excreted from the body. KRYSTEXXA is administered as an infusion every two weeks.

In the next slide, you’ll see uncontrolled gout, which is unresponsive to conventional therapies and associated with painful flares and the formation of tophi, as I described earlier. And it’s shown here in these radiographs on the left and patient pictures on the right. You can clearly see the clinical impact of KRYSTEXXA. In clinical trials of KRYSTEXXA, 70% of patients were able to obtain a reduction in the blood uric acid concentration of less than 6 milligrams per deciliter. And that remarkable result is what underpins the clinical effectiveness in here.

With 9.5 million gout patients in the United States and over 100,000 of whom have uncontrolled gout and KRYSTEXXA’s ability to rapidly reverse disease progression, we believe this medicine has the ability to offer a highly effective treatment for a very high unmet medical need.

And with that, I’m going to hand back again now to Vikram to discuss that unmet medical need in further detail. Vikram?

Vikram Karnani

Thanks, Paul. As you heard, uncontrolled gout is a serious but often overlooked rare condition. We see this demonstrated in the uncontrolled gout patient journey. Nearly 80% of uncontrolled gout patients sit within primary care physicians and podiatry offices for years before finally being referred to a specialist.

We’ve also found that only 8% of patients who meet the definition of having uncontrolled gout are able to self-recognize that their gout is indeed uncontrolled. All of this means that there is still a significant unmet need, and we estimate there are more than 100,000 patients living with uncontrolled gout in the U.S.

As of 2023, we have reached annual penetration of roughly 6%, presenting a substantial opportunity to grow with this medicine. However, current patient awareness of KRYSTEXXA remains low at 29%. And as a result, patients often cycle on urate-lowering therapies, or ULTs, unaware that an advanced treatment option to resolve that uncontrolled gout even exists.

Many patients — many physicians reserve KRYSTEXXA for their most severe patients, further delaying time to treatment. By introducing immunomodulation with KRYSTEXXA, this has evolved the standard of care for uncontrolled gout patients and will be key in driving penetration and reaching more of these 100,000-plus addressable patients.

KRYSTEXXA has steadily created momentum for the past several quarters, and the addition of immunomodulation continues to be a driving factor of this success. We have a strong opportunity to build on our efforts in 2023, which brought us to an all-time high of more than 75% immunomodulation used for new patient starts in Q4 last year.

To keep up this momentum, we must elevate the urgency to treat uncontrolled gout by, first, reframing and generating awareness of gout as a serious inflammatory disease that produces systemic urate deposition with dangerous implications; second, focus on improving patient understanding of gout as a progressive disease beyond symptomology and empower them to see treatment beyond oral ULTs; and third, motivate targeted referral physicians to refer uncontrolled gout patients to a gout specialist for treatment advancement.

We are also focusing on driving HCP and patient conviction in KRYSTEXXA as the treatment of choice. This means expanding current KRYSTEXXA writers’ definition of the appropriate patient to drive depth, instilling confidence among non-users that KRYSTEXXA with immunomodulation is the standard of care. And we will drive patient awareness of KRYSTEXXA as the only treatment that has the potential to rapidly resolve uncontrolled gout.

Finally, we must continue improving the patient experience and perceived burden of treatment through current and future life cycle management activities. This will help us prepare for changes in the competitive landscape and pursue new formulations to meet the needs of uncontrolled gout patients. Our current KRYSTEXXA infusion duration is currently more than two hours every two weeks. We are evaluating shorter infusion duration as well as monthly dosing. This has the potential to meaningfully improve the experience and convenience of physicians, patients and sites of care.

I’ll now hand it back to Paul to talk about UPLIZNA or NMOSD.

Paul Burton

Thanks, Vikram. Neuromyelitis optica spectrum disorder, or NMOSD, is a rare systemic, antibody-mediated, autoimmune disease characterized by chronic inflammatory activity and attack of nerve cells. And this leads to demyelination resulting in CNS and neurological symptoms, often with incomplete recovery.

NMOSD can involve multiple different neurological systems, but most notably, involves the optic nerve, the brain and spinal cord. Patients experience unpredictable attacks that can lead to permanent disability from blindness and even paralysis. Symptoms can be severe and often associated with frequent relapses. Some of it symptoms are similar to those seen with multiple sclerosis, and NMOSD is often misdiagnosed as such.

B-cells are part of the adaptive immune system, and they play a critical role in humoral immunity. B-cell function include antibody production, antigen presentation to T cells and cytokine production. Now normally, B-cells use that repertoire to defend us, for example, against foreign pathogens. But in pathological conditions such as autoimmune disorders, these cells may orchestrate an attack on our body’s own tissues. And in NMOSD, the patient produces autoantibodies against a protein called aquaporin-4, and this results in cell damage in the central nervous system.

These autoantibodies are produced by CD19-positive B-cells. UPLIZNA is an anti-CD19 humanized monoclonal antibody that provides targeted, rapid and sustained CD19-positive B-cell depletion. UPLIZNA’s convenient 6-month dosing interval minimizes patient impact and enables long-term adherence to therapy. The clinical effectiveness of UPLIZNA has been demonstrated in trials, where it was shown to provide over a 75% reduction in the risk of developing a clinical NMOSD relapse with an acceptable safety profile.

Let me hand over again now to Vikram to discuss UPLIZNA in further detail. Vikram?

Vikram Karnani

Thanks, Paul. Since UPLIZNA’s approval in 2020, this medicine has experienced rapid evolution and growth both in the U.S. and through our international expansion efforts. We expect there are roughly 10,000 NMOSD patients in the U.S. with about 80% of those patients being appropriate for UPLIZNA. This represents a substantial opportunity for growth in this market.

To deliver on this, we are focusing on driving awareness of the benefits of UPLIZNA beyond attack prevention as well as highlighting our differentiated clinical profile and the clinical significance of CD19 targeting, humanized design and glycoengineering. We are also driving patient initiation and adherence by disrupting this current disease management paradigm and empowering patients to play an active role in their NMOSD journey. This also means encouraging physicians to employ shared decision-making with patients around therapy selection.

By creating a positive patient experience, our goal is to build HCP and patient confidence in UPLIZNA through real-world experience and facilitating peer-to-peer exchange. This speaks to the importance of advocacy and creating community, which, as I shared earlier, is a critical component of a rare disease patient’s journey.

Beyond the U.S., we also have a significant opportunity to reach thousands more patients. Starting with Europe, where we received approval in April 2022, we see potential for roughly 8,000 to 10,000 addressable patients. Our focus now is to leverage the existing global footprint and robust capabilities in Amgen to accelerate adoption in the EU, where we currently have approval, including France, Germany, Italy and Spain, and execute successful launches in the remaining parts of Europe.

We see similar potential for Brazil, which has a comparable patient opportunity to the U.S. and Europe and received approval in December 2022. We are currently rolling out new diagnostic programs and engaging patient advocacy partners to meet the high unmet need in this country.

And finally, we received approval in Canada in January this year. This global expansion is a critical part of UPLIZNA’s long-term growth strategy and a key area that we are already realizing the benefits of the acquisition to deliver results.

With that, I’ll hand it back to Paul to talk about the potential new indications for UPLIZNA, which are also benefiting from our combined organization.

Paul Burton

Thanks, Vikram. So let’s talk about two diseases: IGg-4 related disease and myasthenia gravis. IgG4-RD, as I’ve mentioned several times already, under normal circumstances, B-cells produce antibodies or immunoglobulins, and they play a critical role in protecting us.

Pathologically, though, autoantibodies and B-cells can cause devastating disease. IgG4-related disease is an example of this, and it’s characterized again by CD19-positive B-cells that overproduce IgG4, a member of the immunoglobulin superfamily.

IgG4-RD is a lifelong systemic inflammatory disease, which affect nearly any organ and typically impacts the multiple organs. It’s characterized by silent ongoing organ damage and recurrent disease flare that’s causing accelerated and irreversible organ damage.

Due to its varied presentation and the often slow onset and progressive nature of the disease, IgG4-RD is frequently underdiagnosed. There are no hallmark symptoms of IgG4-RD. The patient experience is entirely dependent on which organ is impacted. Organs most frequently involved include the pancreas and biliary tree, the library and lacrimal glands, the retroperitoneum and lymph nodes.

There is massive influx of IgG4-positive B-cells into organs, and this results in tumor-like inflammatory masses and tissue fibrosis, and that is what causes permanent organ damage. In fact, nearly 60% of patients may have irreversible organ damage at the time of diagnosis.

IgG4-RD is a significant illness. Patients diagnosed with this have a 2.5-fold higher risk of death compared to the population without IgG4-RD. There are currently no U.S. FDA-approved therapies for this condition, and it is predominantly managed with moderate to high-dose glucocorticoids and off-label therapies, which although effective in inducing remission, fail to prevent relapse.

Since IgG4-RD and IgG4 is produced by B-cells, including CD19-positive B-cells, we believe UPLIZNA has the potential to show clinical benefit in this disease. And as such, a Phase 3 randomized, placebo-controlled trial is currently ongoing. The primary endpoint is the time to independently adjudicated disease flare, and we expect top line data to be available in the second half of 2024.

Let’s turn now to myasthenia gravis, another important neurological condition that shares similar underlying autoantibody pathology. Generalized myasthenia gravis, or GMG, is another rare chronic autoimmune disease that causes fluctuating muscle weakness, which can reduce quality of life and cause significant disability. GMG disproportionately affects younger females and older males. And there were two main types of GMG: those that are acetylcholine receptor antibody positive, and those that are muscle-specific kinase autoantibody positive.

In the case of patients with acetylcholine autoantibodies, these autoantibodies damage the neuromuscular junction with a nerve abuts the muscle cell. And this leads to muscle weakness. And similarly, in the case of musk autoantibodies, these autoantibodies interfere with acetylcholine receptor clustering and signaling. And this, again, in turn, leads to muscle weakness.

As noted earlier, common symptoms include muscle fatigue and weakness, drooping eyelids, ptosis, as shown here in the picture, difficulty swallowing, trouble breathing and impaired speech. Treatment options include steroids, colonesterase inhibitors, immunosuppressants, intravenous immunoglobulin, plasma exchange and off-label use of agents like rituximab.

Again, given that UPLIZNA is a highly effective B-cell depletion agent, we have another Phase 3 trial ongoing in GMG. The MINT trial on myasthenia gravis inebilizumab trial is a randomized, double-blind, placebo-controlled trial in adults 18 years and older with myasthenia gravis. The trial is enrolling patients who are both acetylcholine receptor-positive or MuSK antibody-positive. The primary endpoint is change from baseline in the myasthenia gravis activities of daily living profile score. And again, we expect to have top line data in the second half of this year.

I’ll now hand back to Vikram to make some further comments on GMG.

Vikram Karnani

Thanks, Paul. We see significant potential for these new indications and have great confidence in the future growth opportunity for UPLIZNA. To execute on this, we are prioritizing uptake driven by patients naive to biologics as well as patients switching from competitive biologic therapies; driving awareness of UPLIZNA’s benefits beyond attacks and differentiated clinical profile; driving patient initiation and adherence while creating a positive patient experience as well as empowering those patients in their NMOSD journey; expanding our international footprint and realizing our potential in Brazil and Europe; and expanding into IgG4-related diseases and generalized myasthenia gravis with critical Phase 3 data readouts to come in the second half of this year.

With that, I’m going to hand it right back to Paul to share more about TAVNEOS.

Paul Burton

Thanks, Vikram. So let’s transition now to anti-neutrophil cytoplasmic antibody or ANCA-associated vasculitis. It’s a serious systemic autoimmune disease that leads to inflammation and eventual disruption of medium- and small-diameter blood vessels. This inflammatory disease can lead to permanent organ damage and in severe cases, can even be life-threatening.

ANCA-associated vasculitis, or AAV, covers the spectrum of conditions, including granulomatous disease and polyangiitis, as shown in the figure. Standard of care treatments for AAV include high-dose steroids and immunosuppressants. Those regimens are associated with significant safety issues. Multiple adverse effects of courses of steroid treatment are major causes of both short- and long-term morbidity and mortality. Such therapy-related adverse events contribute significantly to patient care costs as well as to the diminution of quality of life for these patients.

Approximately 80% to 90% of AAV patients present with severe disease as defined by life- or organ-threatening manifestations. And these include limb and digit ischemia, total or partial loss of sight, total or partial hearing loss and facial disfigurement. Relapses are common, and they can cause permanent organ damage as well.

Despite improvements in the knowledge and diagnosis of GPA and MPA, several challenges to disease management continue to exist. And we’ve heard about some of them. They include delays in diagnosis and delays in referral of patients, very important; difficulties in achieving remission with induction therapy; challenges in sustaining remission by preventing relapse; toxicity associated with the use of glucocorticoids; impact on organ function; and finally, the effect on patients’ quality of life.

TAVNEOS is approved by the FDA as an adjunctive treatment of ANCA-associated vasculitis. It’s a first-in-class, orally administered small molecule that is an antagonist of the complement C5a receptor. TAVNEOS employs a novel highly targeted mode of action in complement-driven autoimmune and inflammatory diseases. While the precise mechanism of benefit of TAVNEOS in AAV has not been definitively established, TAVNEOS by blocking the complement 5a receptor C5AR is presumed to reduce the pro-inflammatory activity of neutrophils, an important cellular driver in the disease process of AAV. But importantly, TAVNEOS’ selective inhibition of only the C5a receptor leaves the beneficial C5a pathway through the C5L2 receptor intact and functioning normally.

On this slide, I want to illustrate the clinical benefit that TAVNEOS provides. In the ADVOCATE trial, patients were evaluated for remission at week 26 and sustained remission at week 52. At week 26, TAVNEOS regimen was noninferior to standard therapy in achieving remission. At week 52, the TAVNEOS regimen was superior to standard therapy in sustaining remission. And in this slide, I’m showing you the rates of relapse after remission. And you can see that TAVNEOS reduced the risk of disease relapse by 54%.

And with that, let me hand back now to Vikram to make additional comments on TAVNEOS and its place in the management of patients with AAV. Vikram?

Vikram Karnani

Thanks, Paul. TAVNEOS represents a significant advancement in treatment options for the roughly 10,000 U.S. patients per year that develop severe active disease or experience major relapses of ANCA-associated vasculitis. To date, there have been roughly 2,700 patients treated with TAVNEOS in the U.S. This represents a solid growth opportunity and a chance to leverage our leadership in both to drive results.

To do this, we will establish TAVNEOS as the standard of care in severe active GPA and MPA. The immediate need and our primary population are those with severe active disease. However, we will continue to expand TAVNEOS data set in ANCA-associated vasculitis.

To establish TAVNEOS as the standard of care in severe active GPA and MPA, we will also ramp up our advocacy efforts, increasing awareness and safety and efficacy. We plan to also educate external stakeholders on data supporting its use as an adjunctive therapy for patients experiencing new, relapsing or persistent disease activity. This means continued education to nephrologists and rheumatologists on our data that TAVNEOS sustained remission, reduced the risk of relapse and glucocorticoid loads across these populations. We plan to continuously generate real-world evidence across multiple organ manifestations and patient types, disease activity and duration of use and use data to locate patients at specific points in their journey to enable timely, targeted educational outreach to health care providers.

From a resourcing perspective, we have recently expanded the dedicated TAVNEOS sales force from 52 at ChemoCentryx to 92 in addition to leveraging our existing presence in rheumatology and nephrology in a targeted way. Amgen has experienced integrating complex data sets and deploying to deliver the right message to the right customer for the right patient. This is a key capability that has been optimized on TAVNEOS and can be foundational to our overall efforts in rare disease commercialization.

So before I hand it off to Jay Bradner, I just want to summarize by saying that as you’ve heard today, our rare disease portfolio is primed for growth driven by key execution priorities for each specific medicine. However, our long-term growth opportunity represents more than just our on-market medicines. And a key driver of this future success will also be our robust pipeline and the advancement of our mid- and late-stage clinical programs.

With the comprehensive strategies of our growth drivers seen here as well as our geographic expansion, the enhancements to our therapies and our pending indications, we are in a solid position to drive long-term meaningful growth and impact the lives of more patients living with rare disease.

Now let me hand it over to Jay Bradner, our Chief Scientific Officer, to share more about the pipeline.

James Bradner

Thank you, Vikram. I’m quite pleased to share the details of this Amgen rare disease pipeline as well as our strategy to advance these targeted medicines in a manner that leverages unique capabilities within Amgen to address intrinsic challenges of rare disease research.

Complexity of these diseases, which is often genetic in origin, demands new approaches to find new therapeutic targets and to direct targeted medicines for their most incisive and mechanistic utility. Amgen is the natural home for rare disease medicines. Beyond the industry-leading strength of our biomanufacturing capabilities, I thought to introduce two enabling research platforms: the center for observational research, or C4; and deCODE Genetics.

These high-technology capabilities and experts allow us to fill critical data gaps, generate groundbreaking insights into disease biology while expediting the development of rare disease medicines. At C4, the integration of patient registries and real-world evidence cohorts accelerate Amgen drug development, providing us a deeper understanding of discrete disease characteristics and the rare disease patient journey. Within C4, we’re able to conduct detailed and truly global natural history study. These data leverage real-world data to understand patient experiences and can potentially enable single-arm registrational studies, further accelerating the drug development process for rare disease medicines.

As shown on the right, within our deCODE Genetics organization, we leverage population scale data sets and advanced analytical capabilities. And there, we elucidate unparalleled insight into human biology. Use of whole genome sequencing in conjunction with proteomics and transcriptomic analysis and integrated with clinical data allows deCODE to unearth invaluable insights into human health.

Imagine the potential of mining 200 petabytes of data that encompasses 3.2 million genotype individuals and 800,000 whole genomes. The development of these medicines will leverage deCODE’s extensive capabilities not only to explore the cognitive biology of rare diseases of interest, but also to consider the mechanistic repositioning of rare disease therapies that may be previously unrecognized, sometimes broader disease settings.

Next to bring to life what I just said, we’ll share an example of a recent work performed by C4 to support TAVNEOS. Let’s begin with the left panel. This line graph displays the cumulative incidence of renal outcomes among patients with granulomatosis, with polyangiitis, so-called GPA, or microscopic polyangiitis or MPA, over years of follow-up, if you look at that X axis. The trend here is starkly evident: renal outcomes, unfortunately, are common complications among these patients with incidents increasing over time from diagnosis.

On the right-hand panel, we see the cumulative incidence of renal outcomes among patients who developed GPA or MPA during the study period. Here, you can see that the occurrence of adverse renal outcomes is quite common despite initiating available therapies for remission induction. As the study concluded after the availability of TAVNEOS in late 2021, TAVNEOS-treated patients represent only a small percentage of patients in this analysis, maybe less than 2%, indicating that the majority of outcomes occurred among patients on standard of care remission-induction therapy.

This study indicates there’s a substantial burden of significant renal disease among patients with newly diagnosed GPA or MPA and in the real-world setting. With C4, we can generate highly informative, multiyear outcomes data without the typical time and investment required for prospective clinical investigation. Next slide, please.

Our rare disease pipeline shown here is characterized by many innovative programs with the potential to reach patients with high unmet need. Notably, we’re advancing studies to enhance the convenience of administering TEPEZZA and KRYSTEXXA to therapies that have already made a profound impact on patients’ lives. We’re also excited about the potential to extend the reach of UPLIZNA for additional indication with two Phase 3 data readouts later this year.

Our rare disease pipeline indeed has multiple disease targeted medicines that represent the potential next wave of innovative rare disease therapies at Amgen. Across the portfolio, we’re advancing five Phase 3 studies and five Phase 2 studies across nine different diseases, a broad and incisive approach to rare disease.

Today, I’m going to highlight three programs that we think hold significant potential for driving additional growth, and more importantly, for offering transformative treatments to patients. These medicines are dazodalibep, daxdilimab and fipaxalparant. Each of these programs has shown promising results in early trials, and we’re committed to rapidly advancing their development.

All right. Let’s start with Sjogren’s disease. As shown here, Sjogren’s is a chronic and systemic autoimmune condition. It’s a considerable challenge to those affected and to the medical community at large. Sjogren’s disease is characterized by the mistaken attack of immune cells on healthy cells, primarily affecting exocrine glands, like the salivary or tear glands. However, about 15% to 20% of patients, the disease transcends these glands to impact multiple organ systems, presenting a much more complex clinical picture.

The majority of individuals living with Sjogren’s are women, echoing the gender disparity observed in so many autoimmune diseases. In the United States alone, we estimate between 250,000 to 350,000 patients with an equal number residing outside the U.S. There is, therefore, a global scale of this disease and an imperative to develop global therapeutic solutions.

Despite the prevalence and severity of Sjogren’s, there are currently no FDA-approved, disease-modifying treatments, no FDA-approved, disease-modifying treatment that can alter or slow its course. Management strategies are, therefore, principally palliative focusing on symptom relief, such as artificial tears or medications for dry mouth, off-label use of topical cyclosporine steroids, sometimes immunosuppressants for symptom suppression.

And given the overexpression of CD40 and CD40 ligand, at sites of inflammation and in circulation in Sjogren’s disease patients, we’re pretty excited about the potential of dazodalibep in this setting. Next slide, please.

dazodalibep is an innovative fusion protein designed to inhibit the activity of the CD40 ligand, the target field of science I’ve worked on for many years and a creative solution. Under normal circumstances, CD40 ligand drives immune responses in the body. However, in the context of certain autoimmune diseases, an overactivation of this pathway leads to unchecked inflammation and progression of autoimmune symptoms.

By targeting and blocking CD40 ligand, dazodalibep mitigates adverse immune responses at their source. We’ve recently initiated a Phase 3 study of dazodalibep in Sjogren’s disease. This pivotal trial marks a critical step forward in our commitment to exploring the therapeutic potential of this medicine for patients afflicted by this devastating disease.

Our decision to advance to Phase 3 was encouraged by promising data from a Phase 2 study, which we’ll briefly review in the next slide. Now these findings have not only reinforced our confidence in efficacy and the safety profile of dazodalibep, but also underscore its potential of the groundbreaking treatment option.

Here, we provide an overview of data from our randomized double-blind, placebo-controlled Phase 2 trial of dazodalibep. This study was designed to evaluate dazodalibep’s efficacy across two distinct Sjogren’s disease patient population. The first group comprised patients experiencing moderate-to-severe systemic disease activity. The second group included patients with moderate-to-severe symptomatology, such as dryness, fatigue and pain but without additional organ involvement.

And if you look at the graph, treatment with dazodalibep showed statistically significant improvements in both patient groups compared to placebo control arm. We regard this as a major advance. This dazodalibep is the only investigational medicine to have reached the primary endpoint in both systemic disease activity and symptomatology-focused patient population within a Phase 2 trial for the Sjogren’s disease in the history of our appreciation of that illness.

Furthermore, I’m pleased to report that dazodalibep was well tolerated throughout the trial, a testament to its potential as a safe and effective treatment option. Currently, there are no FDA-approved, disease-modifying therapies, and so the unmet need is large. And these results position the medicine to have a new path forward in managing this severe illness. Next slide, please.

I’d like to next introduce two more severe diseases that a putative targeted therapy. Idiopathic pulmonary fibrosis is the most common and tragically the most lethal form of interstitial pneumonia, falling within the spectrum of interstitial lung diseases. This rare progressive disease is characterized by inflammation and fibrosis of lung tissue, significantly impeding the ability of the lung to exchange oxygen.

As the name implies, the cause of IPF remains unknown, and this presents a real challenge for the field to develop targeted therapies. In the United States alone, the prevalence of IPF is between 75,000 and 100,000 patients. The prognosis for those diagnosed with IPF is quite stark, and mortality rates are alarmingly high. Median survival times are less than five years after diagnosis.

Patients with IPF typically suffer shortness of breath, chronic dry cough, pulmonary insufficiency. And all of these together profoundly affect quality of life and often the ability to perform even basic tasks. Currently, the treatment landscape for IPF is quite limited. While antifibrotic medicines exist that may slow the progression of the disease, they fall well short of being a cure, are often poorly tolerated and lead to many patients discontinuing treatment.

On the right, we introduced diffused cutaneous systemic sclerosis. This is a comparably debilitating also chronic autoimmune disease, characterized by thickening of the skin and fibrosis across multiple organs. This condition stems from an overproduction of collagen and other extracellular matrix components that affect blood vessels and tissues throughout the body, hence its name systemic sclerosis.

In the United States, we estimate there are about 35,000 patients living with this condition. It disproportionately affects women again and also black individuals and is regrettably accompanied by one of the highest mortality rates among all rheumatologic diseases. The severity, complexity of systemic sclerosis with widespread organ involvement both underscore the urgent need for effective treatments.

The landscape of therapy for systemic sclerosis is quite barren. While some immunosuppressants may offer improvement, the only agent has shown any efficacy in slowing progression of lung disease is tocilizumab. And so there’s been a significant unmet need for medicines that can target the underlying pathobiology and offer hope for disease modification and improved outcomes.

Enter fipaxalparant, a small molecule designed to target one of the key drivers of fibrosis and inflammation: a lysophosphatitic acid receptor 1 or LPAR1. Fipaxalparant represents a potential breakthrough in our understanding and approach to treating fibrotic diseases by selectively blocking this receptor, LPAR1. The rationale for targeting LPAR1 is grounded in a robust and largely published body of evidence that underscores a pivotal upstream role in the pathogenesis of fibrotic diseases. This regulated LPAR1 signaling is thought to be a driver of the fibrotic process and activated fibroblast, contributing to tissue remodeling and ultimately scarring that characterize these conditions clinically.

Fipaxalparant potently inhibits LPAR1 signal, which when disregulated leads to the development of leaky blood vessels, inflammation and the fibrosis we’ve been speaking of. Now notably, this medicine is quite selective, and it preserves the normal signaling through other LPA receptors. This targeted mechanism of action that holds real promise to arrest the progression of unchecked fibrosis and inflammation in diseases such as IPF and systemic sclerosis.

We have ongoing two separate Phase 2 studies to explore the efficacy and safety of fipaxalparant in addressing IPF and systemic sclerosis, and we eagerly await the data readout from the first of these studies in the second half of 2024.

On the next slide, I introduce two additional rare diseases that are focus of interest at Amgen: Discoid Lupus Erythematosus, or DLE, is a scarifying form of lupus, primarily affecting the skin, leading to red, scaly, thick skin lesions, most commonly on the scalp, the face and ears. Discoid lupus can result in permanent scarring, irreversible hair loss, skin discoloration if not treated. The visual psychological impact of this disease on patients shouldn’t be understated and there’s a pressing need for effective therapy.

Primary discoid lupus in the form of the disease where the manifestations are limited solely to the skin without systemic involvement, that’s pretty rare. This rarity adds layers of complexity to develop effective treatments as the disease mechanisms are generally less well understood than those of systemic lupus erythematosus, which affects multiple organs.

In the United States, primary discoid lupus affects fewer than 40,000 patients, but its impact is profound, most commonly affecting women in the fourth and fifth decades of life. Furthermore, primary discoid lupus shows a higher prevalence among non-Latino black and Latino patient population, underscoring the need for fundamental research to explain this observation and treatment strategies that address some of the unique needs of these communities.

On the right, myositis encompasses several conditions, including dermatomyositis and antisynthetase inflammatory myositis, or ASIM, as I’ll refer to going forward. Dermatomyositis principally affects the small blood vessels supplying skin and muscle, whereas ASIM more directly affects muscle fibers or the cellular machinery responsible for protein synthesis.

In the United States, there are about 40,000 patients suffering from these conditions, which are more common again in women and black individuals, typically manifesting in mid- to late life. The symptoms of dermatomyositis and ASIM include muscle weakness, joint stiffness, fatigue and for some significant lung disease. Dermatomyositis uniquely affects the skin, while ASIM is impacting very widely, as I’ve mentioned, affecting multiple body systems.

Current treatment approaches, while effective to a degree, leave a lot to be desired. Systemic corticosteroids, general immunosuppressants and intravenous immunoglobin are the current standard for dermatomyositis with ASIM treatments following a similar, more symptom-directed approach. But the side effects of these treatments can be very challenging, and the lack of timely disease control increases the risk of permanent muscle damage. So there’s a huge unmet need for new therapies that target the underlying mechanisms more effectively.

Enter daxdilimab, an anti-ILT7 monoclonal antibody, a human monoclonal antibody as a new approach targeting and managing autoimmune diseases. This advanced agent binds to a deplete plasmacytoid dendritic cells, which presents antigens to the immune system and are therefore central to the pathogenesis of several autoimmune conditions, including lupus. In these diseases, dendritic cells accumulate in tissues in high numbers, and they’re locked in a state of constant activation. The result is the secretion of large quantities of inflammatory signaling molecules, like type 1 interferons, and this contributes significantly to the development of the manifestation of lupus.

We presently have daxdilimab in Phase 2 development for two indications, primary discoid lupus and dermatomyositis, including ASIM. The selection of these indications for Phase 2 development is quite strategic, focusing on areas with, again, really high unmet need and where daxdilimab’s mechanism of action can potentially have the most profound impact. Our aim is not just to treat the symptoms of these autoimmune diseases but to alter their course, here targeting one of the underlying causes of inflammation, the activated plasmacytoid dendritic cell.

Well, in closing, I’m quite excited about the potential of these rare disease investigational medicines that could reach so many more patients suffering from rare and devastating diseases so often underserved by the medical community. And I’ll now turn it back over to Murdo.

Murdo Gordon

Thanks, Jay. It’s been a real pleasure to have reviewed our rare disease growth pillar. So thank you for taking the time to be with us. We really are pleased with the opportunity to serve many, many more patients suffering from rare disease and addressing their unmet need. Amgen has got a strong track record over many decades in both rheumatology and nephrology. And we look forward to leveraging our already well-established capabilities in these areas to serve more patients.

Rare disease makes financial sense. Not only will rare disease be additive to long-term revenue growth, but we anticipate that the Horizon deal will be accretive to our non-GAAP earnings per share in 2024. So at the heart of this new pillar is the strong pipeline, as you’ve heard, a very strong in line portfolio of innovative products and medicines. And we expect to work very, very hard and swiftly to develop this portfolio and to double down on underscoring our dedication, not only to near-term growth but also to sustained long-term expansion. The in-line products are early in their life cycle, and they offer numerous avenues for growth. So I’m really looking forward to serving many more patients with rare disease along with my colleagues that you’ve heard from today.

And with that, I will turn it over to Justin.

Justin Claeys

Great. Thank you, Murdo. We’ll start our Q&A in just a moment and are joined by additional members of the Amgen team as needed. For today’s Q&A session, let me ask our participants to focus your questions on rare disease. The IR team will be available after the call to cover any questions beyond rare disease.

Julienne, if you would please remind our participants of the procedures, and we can start the Q&A.

Question-and-Answer Session

Operator

[Operator Instructions] Our first question will come from Jay Olson from Oppenheimer.

Jay Olson

Thank you for the comprehensive update. Maybe for TEPEZZA, can you talk about how you plan to increase the diagnosis and treatment rates for low CAS patients, not just in the U.S. but globally? And also, do you have any particular plans to address the opportunity for TEPEZZA in China that you could share with us?

Murdo Gordon

Thanks for the question. Jay, maybe I could ask Vikram to comment.

Vikram Karnani

Yes. Thanks, Murdo. Thanks for the question, Jay. I think if you think about the low CAS segment, as I mentioned earlier, what we have seen is already in 2023, we started to build the U.S. TED market following the FDA’s April ’23 label update to treat patients — TED patients regardless of disease activity or duration.

And through those efforts, we have seen a record number of new and unique TEPEZZA prescribers, total patient enrollment forms and patient starts. In fact, we saw an increase of 30% for the prescribers, such as endocrinologists and comprehensive ophthalmologists, which is where you tend to typically find a lot of the low CAS patients.

I think what is critical here is also, as I described back in the patient journey. One of the main hurdles in the patient journey is coverage or access. As I mentioned in my remarks earlier, we have obtained favorable policy changes for greater than 50% of U.S. covered lives to help eligible patients get access to TEPEZZA. Continuing this education and continuing this momentum throughout 2024 is going to be important in addition to providing very robust patient services so that patients can get access to the medicine.

Maybe I’ll take a second here and just talk about the fact that when we highlighted that patient journey, over the last several years, our focus has been on the high CAS patient, which you find with — typically with the key specialists like oculoplastic surgeons, neuro-ophthalmologists, strabismus specialists. However, when you expand to the low CAS population, now you’re talking about new prescribers like endocrinologists and ophthalmologists.

You have to reintroduce how a patient journey takes place in rare disease with these new prescribers. And so it’s not only just educating the prescribers, it’s educating newer patients that have a different manifestation of the disease. And that’s what we’ve been focused on. And we are thrilled with the progress that we have made, and we’ll continue to make the progress throughout the rest of this year.

And maybe, Murdo, I’ll turn it back to you for the question on international and China.

Murdo Gordon

Yes. Perfect. Thanks, Vikram. And Jay, just on international expansion, given the affiliate structure that Amgen has in our presence in over 100 markets, we’re really quite excited about being able to bring TEPEZZA to more patients internationally. And we’re looking broadly at opportunities that might exist in various markets around the world, and we’re moving quickly as well. So you can expect to hear more about the international expansion and launches around the world as we get there.

Operator

Our next question comes from Michael Yee from Jefferies.

Michael Yee

I guess I will skip a question on TEPEZZA. Can you actually talk about your IPF compound? You made a bunch of comments on that. You have data this year. We were trying to look at some of the data from Bristol. Can you maybe just talk a little bit about how that compares, what you can say about your compound and your confidence in that data given what Bristol has shown?

Murdo Gordon

Jay, do you want to take that one?

James Bradner

Yes. I’m happy to start here and accompanied by Macal, who leads the therapeutic development of this medicine. The reason we think it will be successful is that in these fibrotic diseases, this LPA signaling is measurably disregulated, and blocking this pro-inflammatory pathway is a strong mechanistic hypothesis.

As you cite and as you know, idiopathic pulmonary fibrosis and the interstitial lung diseases have proven a very challenging domain for the development of medicines. And so the — at a high level, what we would hope for in developing this medicine is to demonstrate a foothold from this Phase 2 readout plan for the second half of this year, work with regulatory authorities to design and execute a Phase 3 program. And without a lot of effective therapies, I think that the field is wide open for something truly active, if not disruptive.

I really won’t comment on our competitor molecules. But I guess, both mechanistically and what we’ve seen preclinically, we’re encouraged by the development of fipaxalparant. [indiscernible], anything you would add?

Unidentified Company Representative

Thank you, Jay. I think you’ve covered it good enough. We look forward to the data from our assets and head to 2024.

Operator

Our next question comes from Yaron Werber from TD Cowen.

Yaron Werber

Maybe just a couple. Just the first one, it is on TEPEZZA. It sounds like you’re not going to be using the Halozyme technology using your own subcu version. Can you give us a sense ultimately how they’re different? And then secondly, with respect to UPLIZNA, how is the B-cell depletion different than anti-CD20s and for MG or GMG? Do you think you’ll have a broad-enough therapeutic window just given the competition is pretty clean?

Murdo Gordon

Yaron, thanks for the question. We’re not disclosing the mechanism that we’re developing for subcu formulation at TEPEZZA. We’ll talk to you more at a later date about what we’re doing with that. But perhaps I could ask Jay to comment on your question around UPLIZNA.

James Bradner

Yes. No, thanks for the question. As a hematologist with some real familiarity with B-cell depleting strategies. And one of the benefits of targeting CD19 is that we can really deplete the entire of the B-cell compartment, not just limited to, say, mature B-cells or germinal center B-cells only. And this is important because B-cells are involved before germinal centers are formed in the acute reaction to an antigen, and then ultimately, to elaborate a large autoantibody immune response.

So far, UPLIZNA has demonstrated to be a well-tolerated medicine. And we, as a field, have learned how to manage some of the potential challenges of B-cell depletion, and many patients live a long, long time on B-cell depleting therapies. So I think the real differentiator here is mechanistic, taking out the whole of the B-cell compartment so thoroughly and deeply suppress autoimmune pathogenic signaling.

Operator

Our next question comes from Salveen Richter from Goldman Sachs.

Unidentified Analyst

This is Matt on for Salveen. I was hoping you could speak a little more to the current marketplace for gMG. It looks like IQVIA data suggest the market is around $1 billion in the U.S. with a big chunk of this is coming from Soliris and Ultemiris. So just wondering if that sounds accurate. And then for the upcoming Phase 3 data, what kind of benefit on MG-ADL would be meaningful? It seems like current therapies are around 1.6 to 2.6 over various time frames. So just wondering what you think is the bar.

Murdo Gordon

Matt, thanks for the question. We might have to tag team on this one. Vikram, do you want to talk about the gMG opportunity? And then Jay will comment on the second part of the question.

Vikram Karnani

Yes, sure. We think that in terms of GMG, in the U.S., we believe the prevalence to be about — roughly about 55,000 patients. That’s — and I think maybe — there was a follow-up question. I think, maybe around the size of the market in dollars. I don’t think we’re focused right now on our Phase 3 studies. And as we progress to launch, we’ll talk about pricing in due course.

Operator

Our next question comes from Mohit Bansal from Wells Fargo.

Unidentified Analyst

This is [indiscernible] for Mohit. For TEPEZZA subcu, is it more of a defensive strategy against future competition? Or can you potentially see it growing, the opportunity, in low CAS patients? And also, is there any market research you could share on preference for subcu over IV?

Murdo Gordon

Yes. Thanks for the question. I’ll ask Vikram to comment in a minute. Look, one of the things that we were excited about when we took a look at the Horizon in-line portfolio and pipeline was how well it fit with our experience here at Amgen and developing new formulations and new deliveries and devices for complex biologics. I mean this is something that Amgen has over four decades of experience with. So we feel confident that we can definitely facilitate and improve the patient experience with products like TEPEZZA. And I would say that we see it as beyond a competitive position, but something that we need to do given the leadership position we have in the market in serving thyroid eye disease patients. But Vikram, I’ll turn it over to you for additional comments.

Vikram Karnani

Yes. Thanks, Murdo. And I think your comments are exactly spot-on. Look, the — this is all about having a good, positive patient experience. There are — we’ve seen this in multiple therapeutic areas and multiple disease states that there are always going to be patients that will — and physicians for that matter, that will prefer a subcutaneous injection as opposed to an IV infusion.

So our motivation to develop subcu is completely driven by the stated preference or the needs in the marketplace. I think if you also go back and tie this back to the patient journey, right? At the end of the day, the one thing that we have done over the last four years have clearly understood the patient journey for this debilitating disease, right? We have looked at what it takes to activate patients, what it takes to identify patients and diagnose patients, how much time do they spend in the, call it, the stage where they’re trying to receive access and gain payer approval, finding a site of care, which is not trivial, right?

So knowing — having knowledge of all of those various stages of the patient journey allows us to effectively develop the best commercial model and the best care model that will benefit the most amount of patients regardless of whether it’s IV or subcu. So this could have benefit across both segments, whether it’s low CAS or high CAS, but it’s driven by patient preference and our extremely detailed knowledge of that complex patient journey for TED patients.

Operator

Our next question comes from Evan Seigerman from BMO Capital Markets.

Conor Mackay

This is Conor Mackay on for Evan. As you think about expanding in rare disease, can you just talk a little bit about the synergy you expect to realize as it relates to minimizing SG&A and just trying to maximize the revenue opportunity here?

Murdo Gordon

Yes. Thanks, Conor, for the question. Look, the opportunity in rare disease, as we said earlier, is — from a financial standpoint, is a really attractive one. These are products that carry a good strong margin. The SG&A opportunity here, through some of the purchasing power, if you will, and potential for the Amgen capabilities, think international expansion, are extensive. So we think this is a very efficient deal for us. We’ve talked about this being a revenue-driven deal and not a synergy-driven one, but we do expect to be able to realize some SG&A efficiencies. But this is definitely a deal that we continue to focus on for investment as we’ve done with TAVNEOS, and drive that growth in these young products and help the many more patients that are suffering from rare disease.

Operator

Our next question comes from Robyn Karnauskas from Truist Securities.

Robyn Karnauskas

Thanks for giving us a deep dive into the pipeline. I guess, first for TEPEZZA, how do you think about the impact of the label with the hearing loss and uptick in cash? And how do you think about the competitive landscape of IL-6, FCRM? I know they may not be as potent, but they may not have the side effects. How are you thinking about that landscape?

Murdo Gordon

Thanks for the question, Robyn. Maybe I can ask Paul to address the hearing loss label update and then Vikram on the competition.

Paul Burton

Yes. Okay. Thanks, Murdo. Robyn, make just a few comments. I think the first thing is, as we’ve heard, thyroid eye disease is really very significant illness. TEPEZZA has very effectively been shown to treat this severe and debilitating condition. And we are very confident in the benefit-risk profile that TEPEZZA has in these patients.

Then we know that IGF-1 can be implicated in hearing function. That was known from the outset. It was carefully examined and make clinical trials. And we’ve continued to do that in the real-world setting. Hearing impairment was added to the original package insert, and we’ve recently updated the PI to include now warnings and precautions and gives us an opportunity to educate further to talk to physicians about it and also to ensure that testing is done.

Because recall as well, many of these patients suggest that, that age in life where they may be more susceptible to hearing loss. So we’re working with professional scientists and we’re working with HCPs. But we have not actually seen that this is a barrier to use or to growth. And I think that’s in very large part because of this very favorable benefit-risk profile that the medicine has.

Vikram Karnani

Thanks, Paul. I’ll pick it up from there on the question about competition. Look, TEPEZZA has quickly become the standard of care, right? And the bar is pretty high. We’ve set a pretty high bar. I mean, if you think about overall response rate, 83%; proptosis response rate, 90%. And then we followed that up with data from our Phase 4 trial for low CAS patients.

It’s — I think that beyond the efficacy and beyond the fact that this has become the standard of care, we believe that by the time any other competitor comes to the market, not only do we have a very well-established position with robust clinical and real-world evidence that gives us a competitive advantage, but I think it’s really important — again, I’ll go back to what we highlighted earlier about the capabilities that have been built over time to support rare disease patients, right?

Having strong patient support, strong patient advocacy, strong patient services, these are capabilities that must be built. So working in rare disease is beyond just the medicine. And if it is — it has been very important for us to have developed these capabilities to help manage their patient journey.

I think that by the time any other competitor comes to the market, we will have not only established the standard — TEPEZZA as a standard of care from a clinical standpoint but also from a patient support standpoint. So we are — we continue to closely monitor the competitive environment. We’re working on several programs, including the subcu program that we just talked about, how to enhance our TEPEZZA offering for patients, both in high CAS and low CAS settings for the future.

Operator

Our next question comes from Chris Schott from JPMorgan.

Christopher Schott

Just had a question on, I guess, dazodalabab, I don’t know if I pronounced that right, the CD40. Just as we think about market sizing here, I guess, what percent of the Sjogren’s market do you think is most appropriate for this drug as we think about those with high systemic disease or high patient-reported symptoms? Just trying a sense of that, I guess, 250,000 or 300,000 patients. Like what percent are kind of really the target population you’re looking at?

Murdo Gordon

Thanks, Chris, for the question. Vikram, do you want to talk about the opportunity size there?

Vikram Karnani

Yes. Murdo, I’m not sure that we have publicly — previously talked about the patient sizing or the market. I think we’ve been very focused on our clinical program. And I think — and I know that Jay just provided a really comprehensive benefit recap. I think maybe the one thing to point over here is that our ex U.S. or OUS prevalence is also similar in size to that 250,000 to 350,000 patients. And more importantly, there are no FDA-approved, disease-modifying treatments for this area.

Operator

Our last question will come from Gregory Renza from RBC Capital Markets.

Unidentified Analyst

This is [indiscernible] on for Greg. I have a question for UPLIZNA in — opportunity in IgG4-related disease as a potential first FDA-approved therapy. And then secondarily, could you perhaps — based on the B-cell-depleting mechanism, is that an appetite to explore additional indications such as lupus?

Murdo Gordon

Thanks for the question. Jay, do you want to jump in there?

James Bradner

Yes. No, I’d happily take this question. There are a number of mechanisms in our portfolio that we might deploy to study lupus where, for sure, the pathogenic B-cell figures prominently in the biology of that disease. And we are assessing right now across three or four really targeted — B-cell targeting agents within our portfolio, which among them will be most appropriate for a study in systemic lupus erythematosis, which I believe you’re asking about. But I could imagine that UPLIZNA with its mechanism could be quite active in that disease setting. This is all under quite active consideration.

Murdo Gordon

Great. Thank you, Jay. And just in closing, let me again thank everyone for your time today. As I hope you heard, we’re very enthusiastic about rare disease as our newest pillar of long-term growth, and we appreciate you taking the time to join us today on the call.

Operator

This concludes Amgen’s Rare Disease Investor Analyst Call. You may now disconnect.