Zenas BioPharma Announces Successful Phase 3 INDIGO Study of Obexelimab in IgG4-RD
Zenas BioPharma has announced positive top-line results from its pivotal Phase 3 INDIGO clinical trial evaluating obexelimab for the treatment of IgG4-Related Disease (IgG4-RD). IgG4-RD is a rare, systemic, chronic fibroinflammatory condition that can affect multiple organs, including the pancreas, salivary glands, and kidneys, often leading to organ dysfunction or failure if untreated. Obexelimab is a first-in-class, high-affinity, bifunctional monoclonal antibody that mimics the action of antigen-antibody complexes by co-engaging CD19 and FcγRIIb to inhibit B-cell lineage activity.
The INDIGO study was a global, randomized, double-blind, placebo-controlled trial designed to assess the efficacy and safety of obexelimab in patients with active IgG4-RD. The study met its primary endpoint with high statistical significance, demonstrating a substantial reduction in the risk of a “flare” compared to placebo. Secondary endpoints, including clinical remission and reduction in corticosteroid use, also showed favorable results. Crucially, obexelimab achieved these outcomes while maintaining a well-tolerated safety profile, with no new or unexpected safety signals.
This success is a landmark for Zenas and the IgG4-RD community. Currently, there are no specifically approved therapies for this condition, with physicians relying heavily on long-term corticosteroid use, which carries significant side-effect burdens. By providing a targeted, B-cell-modulating therapy that does not deplete B-cells, rather, it inhibits them, Zenas is offering a potential new standard of care. This “B-cell rheostat” approach could enable long-term disease control without the profound immunosuppression associated with traditional B-cell depletion, positioning obexelimab as a significant commercial asset in the rare-disease space.
Sanofi’s Tzield Receives US Priority Review for Stage 2 Type 1 Diabetes in Young Children
Sanofi announced that the U.S. FDA has accepted a Supplemental Biologics License Application (sNDA) for Tzield (teplizumab-mzwv) with Priority Review. The application seeks to expand the drug’s indication to include the delay of the onset of Stage 3 Type 1 Diabetes (T1D) in pediatric patients aged 8 years and older who are currently in Stage 2. Stage 2 T1D is characterized by the presence of two or more islet autoantibodies and abnormal blood sugar levels, though the patient remains asymptomatic. Priority Review status is granted to drugs that offer major advances in treatment, shortening the FDA’s goal for a decision to six months.
The sNDA is supported by data from the PROTECT Phase 3 trial, which evaluated the safety and efficacy of teplizumab in children and adolescents. The study showed that teplizumab effectively preserved beta-cell function, measured by C-peptide levels, thereby slowing the progression toward insulin dependence (Stage 3). Teplizumab works by binding to CD3 on T cells, modulating the autoimmune attack that destroys insulin-producing cells. By intervening during Stage 2, clinicians can significantly delay the life-altering diagnosis of clinical T1D, reducing the immediate risk of diabetic ketoacidosis (DKA) and the long-term risk of cardiovascular and renal complications.
If approved, this expansion would represent a paradigm shift in how early-stage T1D is managed in the pediatric population. It would solidify Tzield’s role as the first and only disease-modifying therapy for T1D, shifting the focus from reactive insulin replacement to proactive beta-cell preservation. For Sanofi, which acquired Provention Bio (the original developer of Tzield) for $2.9 billion, this milestone is key to maximizing the drug’s commercial potential and establishing a dominant position in the “preventative” diabetes market.
Axsome’s AXS-05 sNDA Accepted by FDA with Priority Review for Alzheimer’s Agitation
Axsome Therapeutics announced that the U.S. FDA has accepted the sNDA for AXS-05 (dextromethorphan-bupropion) for the treatment of agitation associated with Alzheimer’s disease. The FDA has granted the application Priority Review, reflecting the urgent unmet medical need for this patient population. Agitation is one of the most distressing neuropsychiatric symptoms of Alzheimer’s, affecting up to 70% of patients and often leading to early institutionalization and increased caregiver burden. AXS-05 is a novel, oral NMDA receptor antagonist with multi-modal activity that is already approved for major depressive disorder under the brand name Auvelity.
The filing is supported by the ADVANCE-1 and ACCORD Phase 3 trials. In the ADVANCE-1 trial, AXS-05 met its primary endpoint by demonstrating a statistically significant reduction in agitation scores (measured by the Cohen-Mansfield Agitation Inventory) compared to bupropion monotherapy and placebo. The ACCORD trial, which utilized a randomized withdrawal design, further showed that patients who remained on AXS-05 were significantly less likely to experience a relapse of agitation compared to those switched to placebo. The drug was generally well-tolerated, with a safety profile consistent with its established use in depression.
The acceptance of this sNDA puts Axsome on the path to providing the first NMDA-based therapy indicated explicitly for Alzheimer’s agitation. Currently, physicians often resort to off-label use of antipsychotics, which carry “black box” warnings for increased mortality in elderly patients with dementia. AXS-05 offers a potentially safer and more effective alternative that targets the underlying glutamatergic dysfunction in the brain. For Axsome, this approval would significantly expand the addressable market for its lead asset, transforming the company’s commercial outlook in the neurology sector.
Vanda Pharmaceuticals Announces FDA Approval of NEREUS for Motion-Induced Vomiting Prevention
Vanda Pharmaceuticals has received U.S. FDA approval for NEREUS (tradipitant) for the prevention of vomiting associated with motion sickness in adults. Tradipitant is a potent neurokinin-1 (NK-1) receptor antagonist. NK-1 receptors are located in the brain’s vomiting center and are triggered by Substance P, a neurotransmitter that mediates the emetic response. While other NK-1 inhibitors exist for chemotherapy-induced nausea, NEREUS is the first in its class to be specifically optimized and approved for the treatment of motion-induced emesis.
The approval is based on the results of the MOTION trial, which evaluated the drug in real-world sea travel conditions. Participants treated with tradipitant showed a significantly lower incidence of vomiting compared to those receiving a placebo during high-seas conditions. Crucially, tradipitant demonstrated a favorable side-effect profile, specifically lacking the profound drowsiness and cognitive impairment often associated with standard-of-care antihistamines and anticholinergics used for motion sickness. This allows travelers to prevent nausea without sacrificing their alertness or functional capacity during their journey.
This approval provides Vanda with a unique commercial foothold in a high-volume consumer pharmaceutical market. While many treatments for motion sickness are available over the counter, they are often inadequate for severe cases or are poorly tolerated. NEREUS serves a specialized segment of patients who require robust, pharmaceutical-grade prevention. Beyond motion sickness, Vanda is also investigating tradipitant for gastroparesis and atopic dermatitis, making this approval a critical first commercial launch for a molecule with broader multi-indication potential.
Omeros’ YARTEMLEA Sets Milestone as First Approved TA-TMA Therapy
Omeros Corporation has achieved a historic milestone with the FDA approval of YARTEMLEA (narsoplimab), making it the first approved therapy for the treatment of hematopoietic stem cell transplant-associated thrombotic microangiopathy (TA-TMA). TA-TMA is a rare, devastating, and often fatal complication of stem cell transplantation, characterized by microvascular thrombosis, hemolytic anemia, and multi-organ failure. The uncontrolled activation of the lectin pathway of the complement system drives it. YARTEMLEA is a fully human monoclonal antibody that targets MASP-2, the effector enzyme of the lectin pathway.
The approval follows a successful pivotal trial in patients with high-risk TA-TMA. The study demonstrated that YARTEMLEA significantly improved survival rates compared to historical controls, with treated patients showing substantial improvements in laboratory markers of TMA and organ function. Specifically, the 100-day survival rate for patients treated with narsoplimab was significantly higher than the survival rates typically observed in this high-risk population. The drug achieved these results without increasing the risk of infections, a common concern with broad complement inhibitors, because it selectively targets the lectin pathway while leaving the classical and alternative pathways intact.
YARTEMLEA’s approval is a defining moment for Omeros and a major victory for transplant medicine. Until now, there was no standard of care for TA-TMA, and the mortality rate for severe cases often exceeded 90%. By providing a targeted, pathway-specific inhibitor, Omeros has turned a near-certain death sentence into a manageable condition. For the company, this approval validates its MASP-2 platform and provides a platform for expansion into other lectin-pathway-mediated diseases, such as IgA nephropathy, marking Omeros as a significant player in the high-value rare disease and complement-mediated disorder markets.
