UPLIZNA® (INEBILIZUMAB-CDON) SIGNIFICANTLY IMPROVES GENERALIZED MYASTHENIA GRAVIS SYMPTOMS IN ACETYLCHOLINE RECEPTOR AUTOANTIBODY-POSITIVE PATIENTS OVER 52 WEEKS

Rhea-AI Summary

Amgen (NASDAQ:AMGN) announced positive 52-week data from the Phase 3 MINT trial for UPLIZNA® in treating generalized myasthenia gravis (gMG). The trial demonstrated significant improvement in patients with acetylcholine receptor autoantibody-positive (AChR+) gMG using just two doses yearly after initial loading.

Key findings include:

• 72.3% of AChR+ patients on UPLIZNA achieved ≥3 point improvement in MG-ADL score vs 45.2% for placebo
• Significant change in baseline MG-ADL score (adjusted difference -2.8)
• 69.2% of UPLIZNA patients improved ≥3 points in QMG score vs 41.8% for placebo

The trial was notable as the first Phase 3 study for a biologic incorporating corticosteroid tapering in its protocol. No new safety concerns were identified, with common adverse events including infusion-related reactions, nasopharyngitis, and urinary tract infections. Regulatory filing is expected to complete in H1 2025.

Positive

• Strong efficacy with 72.3% of AChR+ patients showing significant improvement vs 45.2% for placebo
• Convenient twice-yearly dosing schedule after initial loading dose
• First Phase 3 trial incorporating corticosteroid tapering protocol
• FDA granted Orphan Drug Designation for gMG treatment

Negative

• Regulatory approval still pending with submission not expected until H1 2025
• Presence of adverse events including infusion-related reactions

Insights

Financial Analyst

Amgen's positive 52-week MINT trial results for UPLIZNA represent a significant commercial opportunity that could substantially expand the drug's market beyond its current NMOSD indication. The demonstrated efficacy in acetylcholine receptor autoantibody-positive (AChR+) patients is particularly valuable as these patients represent approximately 80% of the gMG population. With an estimated 60,000-80,000 gMG patients in the U.S. alone, this presents a substantial addressable market.

The drug's differentiating factor is its twice-yearly dosing regimen after initial loading, which offers a compelling convenience advantage over competitors requiring more frequent administration. This could drive both patient preference and adherence, potentially commanding premium pricing and favorable formulary placement. The strong efficacy data - with 72.3% of patients achieving clinically meaningful improvement in activities of daily living scores versus 45.2% for placebo - supports a competitive clinical profile.

From a regulatory perspective, the Orphan Drug Designation and planned H1 2025 submission timeline create a clear path to potential commercialization. This aligns strategically with Amgen's expanding neuroscience portfolio following the Horizon acquisition, potentially creating commercial synergies with the company's existing infrastructure.

The multiple near-term catalysts, including the upcoming PDUFA date for IgG4-RD (April 3, 2025) and the gMG filing, provide sequential opportunities for UPLIZNA to expand into different rare disease markets, potentially establishing it as a multi-indication blockbuster within Amgen's portfolio.

Neurology Specialist

The 52-week MINT trial results demonstrate robust and durable efficacy of UPLIZNA in AChR+ generalized myasthenia gravis, potentially addressing significant unmet needs in this patient population. The data shows clinically meaningful improvements across both functional measures, with 72.3% of treated patients achieving significant improvement in daily activities compared to 45.2% with placebo.

What's particularly significant from a clinical perspective is the successful corticosteroid taper protocol integrated into the study design. As the first Phase 3 trial for a biologic to incorporate this element, it addresses one of the most challenging aspects of gMG management – reducing dependency on steroids while maintaining symptom control. This feature alone could represent a paradigm shift in treatment approaches.

UPLIZNA's B-cell depleting mechanism offers a distinct therapeutic approach compared to complement inhibitors and acetylcholinesterase inhibitors currently available. This mechanistic diversity is valuable for patients who don't respond adequately to existing options. The twice-yearly maintenance dosing regimen following initial loading represents a substantial convenience advantage that could significantly improve treatment adherence and quality of life.

The consistent safety profile, primarily characterized by infusion-related reactions, nasopharyngitis and urinary tract infections, suggests manageable tolerability similar to its approved NMOSD indication. This predictable safety profile is particularly important for a chronic condition requiring long-term treatment.

If approved, UPLIZNA would expand the armamentarium available to neurologists treating this challenging autoimmune condition, offering a new option with demonstrated benefits in improving patients' ability to perform daily activities – the ultimate goal of gMG treatment.

Patients Reported Improvement in Ability to Conduct Daily Activities with Twice-Yearly Dosing*

Late-Breaking Data to be Presented at AAN 2025

THOUSAND OAKS, Calif., March 13, 2025 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced new data from the Phase 3, registrational MINT trial evaluating the efficacy and safety of UPLIZNA^® (inebilizumab-cdon) in adults living with generalized myasthenia gravis (gMG). The results demonstrated durable and sustained efficacy of UPLIZNA in patients with acetylcholine receptor autoantibody-positive (AChR+) gMG with two doses a year, following an initial loading dose. Findings will be presented as a late-breaking oral presentation during the American Academy of Neurology (AAN) Annual Meeting on April 8, 2025, in San Diego.

The Phase 3 MINT trial, which was a randomized-control trial, evaluated UPLIZNA in muscle-specific kinase autoantibody-positive (MuSK+) and AChR+ gMG patients, with the MuSK+ group followed for 26 weeks and the AChR+ group followed for 52 weeks. The trial demonstrated continued improvement in efficacy of UPLIZNA compared to placebo (adjusted difference, −2.8, 95% CI, −3.9 to −1.7) as measured by the change in baseline of Myasthenia Gravis Activities of Daily Living (MG-ADL) score in the AChR+ subpopulation through week 52. Among the AChR+ patients in the UPLIZNA group, 72.3% had a ≥3 point improvement in the MG-ADL score, compared to 45.2% in placebo.¹

As previously disclosed at the 2024 American Association of Neuromuscular & Electrodiagnostic Medicine Annual Meeting, the trial met its primary endpoint, with a statistically significant change from baseline in MG-ADL score for UPLIZNA (-4.2) compared with placebo (-2.2) (difference: –1.9, p<0.0001) at Week 26 for the combined study population.

"The 52-week MINT trial results highlight the potential for a new standard of care in gMG, offering durable symptom relief with a simplified treatment regimen," said Jay Bradner, M.D., executive vice president of Research and Development at Amgen. "These findings reinforce UPLIZNA's ability to provide sustained symptom relief with just two doses per year—an important advancement for patients living with generalized myasthenia gravis—while underscoring our commitment to developing transformative  therapies for people facing complex autoimmune diseases."

Change from baseline in the Quantitative Myasthenia Gravis (QMG) score was also greater for patients in the UPLIZNA group as compared to placebo at Week 52 (adjusted difference, −4.3, 95% CI, −5.9 to −2.8). Among the AChR+ patients in the UPLIZNA group, 69.2% improved by ≥3 points in the QMG score, compared to 41.8% in the placebo group.¹

MINT was the first and only Phase 3 trial for a biologic to incorporate a corticosteroid taper into its protocol. Patients who entered the study taking corticosteroids were tapered down starting at Week 4 to prednisone 5 mg per day by Week 24.

"I'm looking forward to further examining the 52-week MINT data with my colleagues in the neurology community at AAN," said Richard J. Nowak, M.D., M.S., global principal study investigator and director of the Myasthenia Gravis Clinic at Yale University. "These results showed that UPLIZNA consistently relieved burdensome symptoms and improved activities of daily living for gMG patients."

No new safety signals were identified. The overall TEAE profile during the study period is consistent with the known safety profile for the approved indication (NMOSD). The most common adverse events included infusion-related reactions, nasopharyngitis and urinary tract infections.

UPLIZNA is currently approved for the treatment of adult patients with anti-aquaporin-4 (AQP4) antibody positive neuromyelitis optica spectrum disorder (NMOSD) and is under priority FDA review for the treatment of Immunoglobulin G4-related disease (IgG4-RD) with a PDUFA date of April 3, 2025. The FDA has granted UPLIZNA Orphan Drug Designation for the treatment of gMG. Regulatory filing activities are underway with submission anticipated to be complete in H1 2025.

*After an initial loading dose.

About the MINT Trial
The MINT trial is a randomized, double-blind, placebo-controlled, parallel-group trial (NCT04524273) evaluating the efficacy and safety of UPLIZNA in adults with gMG. The trial enrolled 238 adults with gMG, including 190 patients who are acetylcholine receptor autoantibody-positive (AChR+) and 48 patients who are muscle-specific kinase autoantibody-positive (MuSK+).

Eligibility criteria at screening and randomization included a Myasthenia Gravis Foundation of America (MGFA) classification of II, III, or IV disease, MG-ADL score between 6 and 10 with greater than 50% of this score attributed to non-ocular items, or an MG-ADL score of at least 11, QMG score of at least 11, and use of a corticosteroid and/or non-steroidal immunosuppressant.

The primary endpoint was change from baseline in MG-ADL score at Week 26 in the combined population. Key secondary endpoints included change from baseline in QMG scores in the combined study population; change from baseline in MG-ADL score at Week 26 for the AChR+ cohort and separately the MuSK+ cohort; and change from baseline in QMG score at Week 26 for the AChR+ cohort and separately the MuSK+ cohort. Patients who entered the study taking a corticosteroid were tapered down to prednisone 5 mg a day, starting at Week 4 to Week 24. The MINT trial also includes an optional three-year open-label treatment period.

About Generalized Myasthenia Gravis (gMG)
Generalized myasthenia gravis (gMG) is a rare, chronic, B-cell-mediated autoimmune disorder that impairs neuromuscular communication and can cause muscle weakness, trouble breathing, difficulty swallowing and impaired speech and vision.^2-4 

Approximately 85% of patients with myasthenia gravis have the generalized form, or gMG.^5,6 

The prevalence and incidence of gMG are increasing worldwide.⁶ There are between 80,000 and 100,000 patients with myasthenia gravis in the U.S.^7,8 Approximately 85% of patients with myasthenia gravis have detectable antibodies against AChR, and approximately 7% have detectable antibodies against MuSK.⁹ Global prevalence is estimated at 2-36 cases per 100,000.¹⁰ The disease is more frequently seen in young women (age 20-30) and men aged 50 years and older.^6,10

B cells are central to the pathogenesis of gMG. The disease is thought to be primarily driven by pathogenic CD19+ plasmablasts and plasma cells that target critical proteins in the neuromuscular junction.^2-4

About UPLIZNA^® (inebilizumab-cdon)
UPLIZNA is a humanized monoclonal antibody (mAb) that causes targeted and sustained depletion of key cells that contribute to underlying disease process (autoantibody-producing CD19+ B cells, including plasmablasts and some plasma cells). The precise mechanism by which UPLIZNA exerts its therapeutic effects is unknown. After two initial infusions, patients need one dose of UPLIZNA every six months.

About UPLIZNA in NMOSD

INDICATION AND IMPORTANT SAFETY INFORMATION

INDICATION

UPLIZNA (inebilizumab-cdon) is indicated for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive.

IMPORTANT SAFETY INFORMATION

UPLIZNA is contraindicated in patients with:

• A history of life-threatening infusion reaction to UPLIZNA
• Active hepatitis B infection
• Active or untreated latent tuberculosis

WARNINGS AND PRECAUTIONS

Infusion Reactions: UPLIZNA can cause infusion reactions, which can include headache, nausea, somnolence, dyspnea, fever, myalgia, rash, or other symptoms. Infusion reactions were most common with the first infusion but were also observed during subsequent infusions.  Administer pre-medication with a corticosteroid, an antihistamine, and an anti-pyretic.

Infections: The most common infections reported by UPLIZNA-treated patients in the randomized and open-label periods included urinary tract infection (20%), nasopharyngitis (13%), upper respiratory tract infection (8%), and influenza (7%). Delay UPLIZNA administration in patients with an active infection until the infection is resolved.

Increased immunosuppressive effects are possible if combining UPLIZNA with another immunosuppressive therapy.

The risk of Hepatitis B Virus (HBV) reactivation has been observed with other B-cell-depleting antibodies. Perform HBV screening in all patients before initiation of treatment with UPLIZNA. Do not administer to patients with active hepatitis.

Although no confirmed cases of Progressive Multifocal Leukoencephalopathy (PML) were identified in UPLIZNA clinical trials, JC virus infection resulting in PML has been observed in patients treated with other B-cell-depleting antibodies and other therapies that affect immune competence. At the first sign or symptom suggestive of PML, withhold UPLIZNA and perform an appropriate diagnostic evaluation.

Patients should be evaluated for tuberculosis risk factors and tested for latent infection prior to initiating UPLIZNA.

Vaccination with live-attenuated or live vaccines is not recommended during treatment and after discontinuation, until B-cell repletion.

Reduction in Immunoglobulins: There may be a progressive and prolonged hypogammaglobulinemia or decline in the levels of total and individual immunoglobulins such as immunoglobulins G and M (IgG and IgM) with continued UPLIZNA treatment. Monitor the level of immunoglobulins at the beginning, during, and after discontinuation of treatment with UPLIZNA until B-cell repletion especially in patients with opportunistic or recurrent infections.

Fetal Risk: May cause fetal harm based on animal data. Advise females of reproductive potential of the potential risk to a fetus and to use an effective method of contraception during treatment and for 6 months after stopping UPLIZNA.

Adverse Reactions: The most common adverse reactions (at least 10% of patients treated with UPLIZNA and greater than placebo) were urinary tract infection and arthralgia.

About Amgen
Amgen discovers, develops, manufactures and delivers innovative medicines to help millions of patients in their fight against some of the world's toughest diseases. More than 40 years ago, Amgen helped to establish the biotechnology industry and remains on the cutting-edge of innovation, using technology and human genetic data to push beyond what's known today. Amgen is advancing a broad and deep pipeline that builds on its existing portfolio of medicines to treat cancer, heart disease, osteoporosis, inflammatory diseases and rare diseases.

In 2024, Amgen was named one of the "World's Most Innovative Companies" by Fast Company and one of "America's Best Large Employers" by Forbes, among other external recognitions. Amgen is one of the 30 companies that comprise the Dow Jones Industrial Average^®, and it is also part of the Nasdaq-100 Index^®, which includes the largest and most innovative non-financial companies listed on the Nasdaq Stock Market based on market capitalization.

For more information, visit Amgen.com and follow Amgen on X, LinkedIn, Instagram,  YouTube and Threads. 

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CONTACT: Amgen, Thousand Oaks
Madison Howard, 773-636-4910 (media)
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References

1. Nowak R, Phase 3 Myasthenia Gravis Inebilizumab Trial (MINT): Efficacy Data in AChR+ Generalized MG Subpopulation Through Week-52 [Late-breaking oral presentation]. To be presented at American Academy of Neurology Annual Meeting (5-9 April 2025). Available at: www.aan.com/msa/Public/Events/AbstractDetails/61470
2. Yi, J. S., Guptill, J. T., Stathopoulos, P., Nowak, R. J., & O'Connor, K. C. (2018). B cells in the pathophysiology of myasthenia gravis. Muscle Nerve, 57(2):172-184.
3. Willcox H. N., Newsom-Davis, J., & Calder, L. R. (1984). Cell types required for anti-acetylcholine receptor antibody synthesis by cultured thymocytes and blood lymphocytes in myasthenia gravis. Clinical and Experimental Immunology., 58:97-106.
4. Stathopoulos P., Kumar, A., Nowak, R. J., & O'Connor, K. C. (2017). Autoantibody-producing plasmablasts after B cell depletion identified in muscle-specific kinase myasthenia gravis. JCI Insight, 2(17):e94263.
5. Lazaridis K., & Tzartos, S. J. (2020). Autoantibody Specificities in Myasthenia Gravis; Implications for Improved Diagnostics and Therapeutics. Frontiers in Immunology, 11:212.
6. Dresser L., Wlodarski, R., Rezania, K., & Soliven, B. (2021). Myasthenia Gravis: Epidemiology, Pathophysiology and Clinical Manifestations. J Clin Med, 10(11):2235.
7. Ye et al. Frontiers in Neurology. (2024);15:1339167.
8. Rodrigues E., Umeh, E., Aishwarya, Navaratnarajah, N., Cole, A., & Moy, K. (2024). Incidence and prevalence of myasthenia gravis in the United States: A claims-based analysis. Muscle Nerve, 69(2):166-171.
9. Hehir, M. K., & Silvestri, N. J. (2018). Generalized myasthenia gravis: classification, clinical presentation, natural history, and epidemiology. Neurologic Clinics, 36:253-60.
10. Bubuioc, A. M., Kudebayeva, A., Turuspekova, S., Lisnic, V., & Leone, M. A. (2021). The epidemiology of myasthenia gravis. Journal of Medicine and Life, 14(1):7-16.

 

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SOURCE Amgen

FAQ

What were the key efficacy results of UPLIZNA in the MINT trial for AMGN's gMG treatment?

72.3% of AChR+ patients on UPLIZNA achieved ≥3 point MG-ADL score improvement vs 45.2% for placebo, with an adjusted difference of -2.8 in baseline MG-ADL score through week 52.

How often do patients need to take UPLIZNA in Amgen's MINT trial for gMG?

Patients receive just two doses per year following an initial loading dose.

When will Amgen (AMGN) submit regulatory filing for UPLIZNA in gMG treatment?

Regulatory filing is anticipated to be complete in H1 2025.

What safety profile did UPLIZNA show in AMGN's Phase 3 MINT trial?

No new safety signals were identified, with common adverse events including infusion-related reactions, nasopharyngitis and urinary tract infections.