Zai Lab and argenx Report Positive Phase 3 Results for VYVGART Hytrulo in Autoimmune Myositis
Zai Lab Limited and argenx have announced positive topline results from the ALKIVIA Phase 3 clinical study evaluating VYVGART® Hytrulo (efgartigimod alfa and hyaluronidase-qvfc) in adults living with autoimmune myositis. The results showed that treatment with efgartigimod produced a statistically significant and clinically meaningful improvement in disease outcomes compared with placebo, potentially supporting a new targeted treatment approach for patients with this debilitating group of autoimmune disorders.
The ALKIVIA study achieved its primary endpoint, demonstrating a statistically significant improvement in the Total Improvement Score (TIS) at Week 52 in the overall study population. Patients receiving efgartigimod achieved a mean TIS of 47.95, compared with 32.56 among patients receiving placebo, representing a 15.4-point greater improvement with efgartigimod. The difference between the treatment groups was statistically significant, with a p-value of 0.0011.
Autoimmune myositis encompasses a group of rare and chronic inflammatory diseases characterized primarily by muscle inflammation and weakness. The condition can significantly interfere with mobility, physical function and everyday activities. Depending on the specific subtype, patients may also experience manifestations affecting the skin and other organs.
The ALKIVIA trial included patients with two major forms of autoimmune myositis: immune-mediated necrotizing myopathy (IMNM) and dermatomyositis (DM). The positive results across the overall population provide evidence that targeting pathogenic immune mechanisms with efgartigimod may have the potential to address multiple aspects of disease activity.
Primary Endpoint Demonstrates Meaningful Clinical Improvement
The primary endpoint of ALKIVIA was the mean TIS at Week 52. TIS is a composite measure designed to evaluate improvements across several important dimensions of myositis, including muscle strength, physical function and disease activity.
The 15.4-point difference between efgartigimod and placebo indicates a meaningful improvement in the overall population after one year of treatment. Importantly, the treatment effect was not limited to a single component of the disease.
All six core set measures contributing to TIS favored efgartigimod over placebo in both IMNM and DM. These measures span areas such as muscle strength, the ability to perform everyday physical activities and broader indicators of disease activity beyond muscle involvement.
The findings suggest that reducing disease-driving immune activity with efgartigimod may provide multidimensional benefits for patients rather than simply improving one aspect of autoimmune myositis.
Benefits Appeared Early and Continued Throughout Treatment
One of the notable findings from the ALKIVIA study was the early emergence and persistence of the treatment effect.
In the combined IMNM and DM population, patients treated with efgartigimod began demonstrating improvements compared with placebo as early as Week 4. The differences between treatment groups were statistically significant and remained sustained throughout the full 52-week treatment period.
The durability of the benefit is particularly important for patients with chronic autoimmune myositis, where maintaining muscle strength and physical function over time can be challenging. The sustained treatment response observed in ALKIVIA continued even as patients underwent steroid tapering.
Corticosteroids have traditionally played an important role in managing autoimmune myositis, but long-term steroid use can create significant challenges and adverse effects. The ability to achieve sustained disease improvement while reducing reliance on corticosteroids could therefore represent an important consideration for future treatment strategies.
Strong Results in Immune-Mediated Necrotizing Myopathy
Prespecified analyses showed that the primary endpoint was also achieved in patients with immune-mediated necrotizing myopathy, or IMNM.
Patients with IMNM treated with efgartigimod demonstrated a mean TIS of 45.05 at Week 52, compared with 30.24 among those receiving placebo. This represented a 14.8-point greater improvement with efgartigimod, with a statistically significant p-value of 0.0048.
The findings are particularly significant because IMNM is considered one of the more severe and difficult-to-treat forms of autoimmune myositis. Patients may experience profound muscle weakness, and in some cases substantial muscle damage can become irreversible.
According to the companies, IMNM currently has no approved therapies specifically indicated for the disease. Consequently, the positive Phase 3 findings could represent an important advance for a patient population with considerable unmet treatment needs.
Clinically Meaningful Improvement Also Observed in Dermatomyositis
The study also showed a clinically meaningful improvement among patients with dermatomyositis, another major form of autoimmune myositis.
At Week 52, patients treated with efgartigimod achieved a mean TIS of 51.51, compared with 36.96 for placebo. The resulting treatment difference was 14.5 points.
Although the difference did not reach statistical significance in the smaller DM subgroup, with a p-value of 0.1093, the magnitude of the observed clinical improvement was comparable to that seen in the IMNM population.
The companies also reported improvements in skin disease activity among patients with DM. This finding is particularly relevant because dermatomyositis can involve both muscle and skin manifestations. Therefore, a treatment capable of improving multiple components of the disease could offer broader clinical value to patients.
Targeting Pathogenic Autoantibodies
Efgartigimod is designed to target the neonatal Fc receptor, or FcRn, a mechanism involved in maintaining circulating levels of immunoglobulin G (IgG) antibodies.
By targeting FcRn, efgartigimod is intended to reduce circulating IgG levels, including disease-associated pathogenic autoantibodies. Autoantibodies are believed to play an important role in several autoimmune diseases, and the ALKIVIA results provide further clinical evidence supporting the potential importance of IgG autoantibodies in autoimmune myositis.
Luc Truyen, M.D., Ph.D., Chief Medical Officer at argenx, said the findings demonstrate that precision targeting of FcRn with efgartigimod can produce meaningful benefits in autoimmune myositis.
He highlighted the early and durable separation from placebo and noted that the treatment effect was of comparable magnitude across IMNM and DM. According to Truyen, these results strengthen the rationale for targeting pathogenic IgG autoantibodies as part of a treatment strategy for autoimmune myositis.
Potential to Reduce Dependence on Long-Term Steroids
For many patients with autoimmune myositis, corticosteroids and broad immunosuppressive medicines have historically been central components of treatment. However, these therapies do not specifically target the underlying mechanisms responsible for disease in every patient and can be associated with significant long-term complications.
The ALKIVIA findings could therefore be important in the search for more targeted treatment approaches.
Rafael G. Amado, M.D., President and Head of Global Research and Development at Zai Lab, said the Phase 3 findings demonstrated a clinically meaningful and statistically significant treatment benefit in the overall population and showed significant improvement among patients with IMNM.
He emphasized the potential significance of these findings for patients in China living with autoimmune myositis, particularly those seeking treatment options that could improve muscle strength, physical function and other manifestations of the disease.
Zai Lab participated in the global ALKIVIA study and plans to work with argenx toward potentially making the therapy available to patients in China, subject to applicable regulatory requirements.
Expert Perspective on the Clinical Significance
Rohit Aggarwal, M.D., M.S., Professor of Medicine and Co-Director of the Myositis Center at the University of Pittsburgh and an ALKIVIA investigator, described the results as significant for a disease area where targeted treatment options remain limited.
He emphasized that improving strength and physical function while helping patients reduce long-term steroid exposure remains an important goal in myositis treatment. He also noted the particular challenge of treating IMNM, where patients can experience substantial and potentially irreversible muscle damage.
The comparable magnitude of improvement observed in the DM population was also highlighted as important. While the statistical significance threshold was not reached in this smaller subgroup, the observed clinical improvement provides additional evidence warranting further evaluation of efgartigimod in dermatomyositis.
Safety Profile Consistent With Previous Experience
Efgartigimod was generally well tolerated in the ALKIVIA study. The safety profile observed in the trial was consistent with the medicine’s established safety profile from previous clinical studies, and the companies reported no unexpected safety findings.
The continued consistency of the safety profile will be important as the companies evaluate the potential use of efgartigimod across additional autoimmune diseases and patient populations.
Further detailed information from ALKIVIA, including the complete efficacy and safety dataset, is expected to be presented at an upcoming medical meeting. The full results will provide healthcare professionals and researchers with additional insight into the magnitude and durability of the treatment response.
Broader Development of Efgartigimod
The positive ALKIVIA results add to the growing clinical development program for efgartigimod. The therapy continues to be investigated across additional autoimmune diseases, including Sjögren’s disease and systemic sclerosis.
The broader development strategy reflects increasing interest in targeted approaches capable of addressing specific mechanisms involved in autoimmune disorders. FcRn-directed therapy represents one such approach, with the potential to reduce pathogenic IgG antibodies while providing a more targeted alternative to broad immunosuppression.
For Zai Lab and argenx, the ALKIVIA results represent an important milestone in expanding the potential applications of efgartigimod beyond its existing development programs.
Overall, the Phase 3 findings provide encouraging evidence that efgartigimod can deliver sustained and clinically meaningful improvements in adults with autoimmune myositis. The statistically significant primary endpoint, positive results in IMNM, clinically meaningful improvement in DM, early treatment response and multidimensional benefits across muscle and disease-activity measures all support continued development of the therapy.
As detailed ALKIVIA data become available and regulatory discussions progress, efgartigimod could potentially emerge as a targeted treatment option for patients with autoimmune myositis, particularly those with IMNM who currently have limited therapeutic choices. The results also reinforce the potential importance of reducing pathogenic IgG autoantibodies as a therapeutic strategy for autoimmune diseases.
About the ALKIVIA Study
The ALKIVIA study was a global, randomized, double-blind, placebo-controlled, multicenter, operationally seamless Phase 2/3 study of efgartigimod SC for the treatment of autoimmune myositis across IMNM, DM and PM. The ALKIVIA study enrolled 264 patients who had active disease and were on background treatment. Participants were randomized (1:1) to receive weekly injections of efgartigimod PH20 SC or matched placebo PH20 SC.
The study was conducted in two phases, with an analysis of the Phase 2 portion of the clinical trial after the first 89 patients completed the study, followed by Phase 3. The Phase 3 study enrolled 175 patients and included a protocol-mandated corticosteroid taper throughout the study. The primary endpoint of Phase 3 was the mean Total Improvement Score (TIS) at the end of the treatment period of 52 weeks of all treated patients compared to placebo. Prespecified analyses evaluated the combined IMNM and DM population and each subtype separately.
argenx has an exclusive license agreement with Zai Lab for the development and commercialization of VYVGART and VYVGART Hytrulo in Greater China. Through this agreement, Zai Lab recruited Chinese patients into the ALKIVIA trial.
About Autoimmune Myositis
Autoimmune myositis is a heterogenous disease spectrum with autoimmune-mediated pathophysiology, characterized by chronic inflammation and progressive muscle weakness, and in some subtypes by skin involvement and other extramuscular manifestations. Proximal muscle weakness is a hallmark clinical feature across subtypes.
Approximately 100,000 people in the United States live with autoimmune myositis, including approximately 20,000 with IMNM and approximately 40,000 with DM. Up to 80 percent of patients report long-term disability despite treatment. There are currently no targeted treatments available, and care relies primarily on corticosteroids and broad immunosuppressants, which are associated with significant cumulative toxicity, including metabolic, cardiovascular, musculoskeletal and infectious complications.
Advances in the understanding of autoimmune myositis biology have highlighted the central role of antibody-mediated immunity, with pathogenic IgG autoantibodies contributing to muscle fiber damage and extramuscular manifestations across subtypes. FcRn maintains circulating IgG levels by recycling IgG antibodies, including pathogenic autoantibodies. Efgartigimod is designed to selectively block FcRn, reducing pathogenic IgG autoantibodies while preserving other aspects of immune function.
About VYVGART
VYVGART® (efgartigimod alfa fcab) is a first-in-class human IgG1 antibody fragment that binds to the neonatal Fc receptor (FcRn), resulting in the reduction of circulating IgG autoantibodies. VYVGART Hytrulo® is a subcutaneous combination of efgartigimod alfa (VYVGART) and recombinant human hyaluronidase PH20 (rHuPH20), Halozyme’s ENHANZE® drug delivery technology to facilitate subcutaneous injection delivery of biologics. VYVGART is approved for generalized myasthenia gravis (gMG) and immune thrombocytopenia (Japan only). VYVGART Hytrulo is approved for gMG and chronic inflammatory demyelinating polyneuropathy (CIDP). VYVGART Hytrulo may be marketed under different proprietary names in other regions.
About Zai Lab
Zai Lab Limited (NASDAQ: ZLAB; HKEX: 9688) is an innovative, research-based, commercial-stage biopharmaceutical company based in China and the United States. We are focused on discovering, developing, and commercializing innovative products that address medical conditions with significant unmet needs in the areas of oncology, immunology, neuroscience, and infectious disease. Our goal is to leverage our competencies and resources to positively impact human health.
About argenx
argenx is a global immunology innovation company committed to improving the lives of people suffering from severe autoimmune diseases. Partnering with leading academic researchers through its Immunology Innovation Program (IIP), argenx aims to translate immunology breakthroughs into a world-class portfolio of novel antibody-based medicines. argenx developed and is commercializing the first approved neonatal Fc receptor (FcRn) blocker and is evaluating its broad potential in multiple serious autoimmune diseases while advancing several earlier stage experimental medicines within its therapeutic franchises.