US FDA Grants Priority Review to Jemperli for dMMR/MSI-H Locally Advanced Rectal Cancer; Amylyx’s Avexitide Achieves Positive Topline Results in Phase 3 LUCIDITY Study; Ultragenyx Marks Major Milestone as FDA Approves GENGLYCOS for GSDIa; Pasatru Receives FDA Approval for Fibrodysplasia Ossificans Progressiva; Merck and Moderna’s Intismeran Autogene Plus KEYTRUDA Delivers Positive Phase 3 Results in Resected Melanoma

GSK’s Jemperli Granted FDA Priority Review for dMMR/MSI-H Locally Advanced Rectal Cancer

GSK plc announced that the US Food and Drug Administration (FDA) has accepted its supplemental Biologics License Application (sBLA) for priority review of Jemperli (dostarlimab) as a potential treatment for patients with previously untreated stage II or III mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) locally advanced rectal cancer. The FDA has set a PDUFA action date for February 2027. The application is also eligible for expedited assessment under the National Priority Voucher program, which may enable an earlier regulatory decision.

Rectal cancer, a form of bowel cancer, affects approximately 770,000 people worldwide each year, with an estimated 5–10% of cases characterized as dMMR/MSI-H. Current standard treatment typically involves chemotherapy, radiation therapy, and surgery. Although these approaches can be effective, they may result in long-term complications affecting bowel, urinary, and sexual function, fertility, and overall quality of life.

The sBLA is supported by positive findings from the registrational Phase II, single-arm AZUR-1 trial. The study achieved its primary endpoint by demonstrating a clinically meaningful and durable clinical complete response lasting at least 12 months (cCR12), with no detectable evidence of cancer for one year or longer. Interim results also showed that dostarlimab had a generally consistent and manageable safety and tolerability profile, in line with previous observations across solid tumors. The data are expected to be submitted for presentation at a scientific meeting later in 2026.

The AZUR-1 findings suggest a substantial improvement over the historical standard of care and support the potential for dostarlimab, if approved, to become the first immunotherapy to eliminate or postpone the need for chemotherapy, radiation, and surgery in certain patients with this disease. The results further build on earlier research conducted with Memorial Sloan Kettering Cancer Center, which demonstrated that dostarlimab could induce clinical complete responses without the use of additional therapies in patients with dMMR/MSI-H locally advanced rectal cancer.

Dostarlimab has previously received Fast Track and Breakthrough Therapy Designations for this indication. The application has also been accepted under Project Orbis, an initiative led by the FDA Oncology Center of Excellence that facilitates coordinated reviews among participating international regulatory agencies and may help accelerate regulatory decisions and patient access. However, regulatory authorities in each participating country will continue to make independent decisions.

Amylyx Reports Positive Phase 3 LUCIDITY Results for Avexitide in Post-Bariatric Hypoglycemia

Amylyx Pharmaceuticals, Inc. announced positive topline findings from LUCIDITY, a Phase 3, multicenter, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of avexitide, an investigational first-in-class glucagon-like peptide-1 (GLP-1) receptor antagonist, in 78 adults with post-bariatric hypoglycemia (PBH) following Roux-en-Y gastric bypass (RYGB) surgery. The trial achieved its FDA-agreed primary endpoint, showing a 55% reduction in the composite rate of Level 2 and Level 3 hypoglycemic events versus placebo through Week 16 (p=0.000003). All secondary endpoints were also met, with consistent, statistically significant, and clinically meaningful reductions in Level 2 hypoglycemic events measured by self-monitoring of blood glucose (SMBG) and continuous glucose monitoring (CGM), as well as Level 3 events.

PBH is a chronic metabolic disorder characterized by recurrent episodes of hypoglycemia that can substantially affect patients’ safety and quality of life. Level 2 and Level 3 events may lead to severe cognitive and physical impairment, loss of consciousness, seizures, and the need for assistance, highlighting the unmet need for an FDA-approved treatment.

The LUCIDITY trial enrolled 78 adults with PBH following RYGB surgery, who were randomized in a 3:2 ratio to receive either 90 mg of subcutaneous avexitide once daily or placebo. The study demonstrated a 55% reduction in the composite rate of Level 2 and Level 3 hypoglycemic events compared with placebo through Week 16 (p=0.000003). Secondary analyses further confirmed significant reductions in SMBG- and CGM-measured Level 2 hypoglycemic events and independently adjudicated Level 3 events.

Avexitide was generally well tolerated during the double-blind treatment period, with a favorable and consistent safety profile in line with findings from five previous PBH clinical trials. Most adverse events were mild to moderate, and no serious adverse events were considered related to avexitide. The most frequently reported adverse events included diarrhea, injection-site erythema, and injection-site bruising.

Amylyx stated that the LUCIDITY findings represent an important step toward addressing the unmet treatment need in PBH. The company plans to submit a New Drug Application (NDA) to the FDA by the end of 2026, while the ongoing open-label extension and expanded access program continue to provide eligible patients with access to avexitide.

Ultragenyx’s GENGLYCOS Receives FDA Approval as First Treatment for Glycogen Storage Disease Type Ia

Ultragenyx Pharmaceutical Inc. announced that the U.S. Food and Drug Administration (FDA) has granted accelerated approval to GENGLYCOS™ (pariglasgene brecaparvovec-opnr), also known as DTX401, for the treatment of adults and children aged eight years and older with glycogen storage disease type Ia (GSDIa).

According to Eric Crombez, M.D., chief medical officer at Ultragenyx, the approval marks a significant milestone in the company’s efforts to address the underlying cause of GSDIa. Clinical studies showed that GENGLYCOS reduced patients’ dependence on cornstarch by restoring the liver’s ability to break down glycogen and generate glucose during fasting or metabolic stress. Improved glucose regulation may reduce the overall disease burden and potentially lower the risk of severe or life-threatening hypoglycemia. GENGLYCOS also represents Ultragenyx’s first approved gene therapy and highlights the company’s growing focus on gene-based treatments for rare diseases.

GSDIa is an ultra-rare inherited metabolic disorder resulting from a deficiency of the enzyme required for the liver to release glucose into the bloodstream. This impaired glucose regulation can lead to potentially life-threatening hypoglycemic episodes and other serious complications. Patients typically require intensive nutritional management, including frequent, around-the-clock consumption of uncooked cornstarch as an oral source of glucose. However, cornstarch-based glucose management can result in substantial fluctuations in blood glucose levels, often leaving patients with prolonged periods of hyperglycemia as they attempt to prevent hypoglycemic events. GSDIa is estimated to affect approximately 1,500–2,500 people in the U.S. and 6,000–8,000 patients globally across commercially accessible markets.

The accelerated approval of GENGLYCOS was supported by results from the 48-week, randomized, double-blind, placebo-controlled Phase 3 GlucoGene study, which enrolled 46 patients aged eight years and older. Participants received either DTX401 at a dose of 1.0 × 10^13 GC/kg or placebo, with the treatment group demonstrating a statistically significant reduction in cornstarch requirements compared with placebo (p<0.001). The modified intention-to-treat (mITT) efficacy population included 44 participants—20 treated with DTX401 and 24 receiving placebo—during the Week 48 assessment period. Eligible participants subsequently crossed over to the alternative treatment. Following crossover, patients continued to be monitored, with additional analyses performed at Weeks 96 and 144.

FDA Grants Approval to Pasatru for Reducing New HO Lesions in Adult FOP

Regeneron Pharmaceuticals, Inc. announced that the U.S. Food and Drug Administration (FDA) has approved Pasatru™ (garetosmab-grts) to help reduce the development of new heterotopic ossification (HO) lesions and clinician-assessed flare-ups in adults living with fibrodysplasia ossificans progressiva (FOP). Given the substantial mobility limitations associated with FOP, Pasatru offers flexibility in administration and may be delivered in various care settings, including home infusion when appropriate. The recommended initial dose is weight-based at 10 mg/kg, administered intravenously over 60 minutes once every four weeks. For patients who do not tolerate the initial dose, treatment may be reduced to 3 mg/kg, also infused over 60 minutes once monthly. Developed using Regeneron’s VelocImmune® technology, Pasatru is a fully human monoclonal antibody designed to inhibit Activin A, a protein identified by Regeneron researchers as a key contributor to HO lesion formation in people with FOP.

FOP is an ultra-rare genetic condition characterized by the progressive formation of abnormal bone within muscles, tendons, ligaments, and other connective tissues, a process referred to as heterotopic ossification. When HO affects areas such as the jaw, spine, hips, and rib cage, it can interfere with essential functions including speaking, eating, walking, and breathing, ultimately resulting in progressive loss of mobility. Approximately 900 individuals worldwide are diagnosed with FOP, with most patients becoming wheelchair-dependent by age 30 and a median survival of approximately 56 years.

According to Dr. Kathryn Dahir, Professor in the Department of Internal Medicine, Division of Endocrinology, Diabetes, and Metabolism at Vanderbilt University and a primary investigator of the OPTIMA trial, each occurrence of abnormal bone formation can further contribute to disability and mobility loss in people with FOP. She noted that the reduction in new bone lesions and flare-ups demonstrated with Pasatru provides patients with an important new treatment option.

The FDA approval was supported by efficacy and safety findings from the positive Phase 3 OPTIMA trial, which evaluated Pasatru in adults with FOP. At week 56, both evaluated doses achieved the primary endpoint, showing substantial reductions in the total number of new HO lesions compared with placebo. Patients receiving Pasatru 10 mg/kg (n=23) experienced a 90% reduction, with 2 lesions compared with 19 in the placebo group (n=21), while those receiving 3 mg/kg (n=19) experienced a 94% reduction, with 1 lesion versus 19 with placebo, based on computed tomography (CT) assessments.

Clinician-assessed flare-ups, a key secondary endpoint, totaled 9 among patients receiving Pasatru 10 mg/kg, representing an 88% reduction versus placebo; 53 flare-ups were reported in the 3 mg/kg group, corresponding to a 15% reduction, compared with 66 in the placebo group. However, the proportion of patients reporting flare-ups through week 56 did not differ significantly between the Pasatru and placebo groups. Among the 63 participants enrolled in the trial, serious treatment-emergent adverse events were reported in two patients receiving 10 mg/kg Pasatru, one receiving 3 mg/kg, and two receiving placebo. Adverse reactions occurring in at least 10% of adults treated with either Pasatru dose included abscesses, acne, increased hair growth, madarosis (eyebrow loss), oral ulcers, epistaxis, folliculitis, paronychia, and rash.

Regulatory review of Pasatru is also underway in the European Union, where the application is being assessed by the European Medicines Agency. Regeneron plans to pursue additional regulatory submissions in other markets, including Japan. Pasatru has previously received FDA Fast Track and Orphan Drug designations, as well as Orphan Designation from the European Medicines Agency and Japan’s Ministry of Health, Labour and Welfare.

Merck and Moderna’s Intismeran Autogene Plus KEYTRUDA Meets RFS and DMFS Endpoints in Phase 3 Melanoma Trial

Merck and Moderna, Inc. announced positive topline results from the Phase 3 INTerpath-001 trial evaluating intismeran autogene (intismeran; V940 or mRNA-4157), an investigational individualized mRNA-based neoantigen therapy (INT), in combination with Merck’s anti-PD-1 therapy KEYTRUDA® (pembrolizumab) as adjuvant treatment for patients with completely resected stage IIB-IV melanoma. The study achieved its primary endpoint of recurrence-free survival (RFS) as well as the key secondary endpoint of distant metastasis-free survival (DMFS). The results mark the first positive Phase 3 readout for an individualized neoantigen therapy and an mRNA-based cancer therapy, and the first Phase 3 trial to demonstrate a clinically meaningful benefit over KEYTRUDA monotherapy in the adjuvant treatment of resected melanoma.

At a pre-specified interim analysis, the combination of intismeran and KEYTRUDA produced statistically significant and clinically meaningful improvements in both RFS and DMFS compared with KEYTRUDA alone in patients with completely resected stage IIB, IIC, III or IV cutaneous melanoma who had not previously received systemic therapy. In line with the study protocol, the trial will continue to assess additional key secondary endpoints, including overall survival (OS).

The safety profile of intismeran combined with KEYTRUDA remained consistent with previously reported findings, with no new safety concerns identified. The companies plan to present the findings at an upcoming international medical congress and submit the data to regulatory agencies.

According to Professor Georgina Long, principal investigator of the study and medical director of Melanoma Institute Australia, the findings represent a significant milestone in adjuvant melanoma treatment. The results demonstrate that intismeran, which is designed according to the unique mutational profile of an individual patient’s tumor, can be combined with pembrolizumab to lower the risk of recurrence or death compared with KEYTRUDA alone in patients with completely resected stage IIB-IV melanoma. The combination could potentially introduce a new treatment approach in the adjuvant melanoma setting and help patients remain free of cancer for longer.

Merck and Moderna are continuing to advance the INTerpath clinical development program, which is assessing the safety and efficacy of intismeran in combination with KEYTRUDA and other anticancer therapies, as well as as a standalone treatment. The program currently includes nine Phase 2 and Phase 3 trials spanning multiple tumor types and disease stages, including melanoma, non-small cell lung cancer (NSCLC), bladder cancer and renal cell carcinoma. The broader development program also includes the Phase 2b KEYNOTE-942/mRNA-4157-P201 trial in adjuvant melanoma and a Phase 1 study investigating intismeran in adjuvant pancreatic ductal adenocarcinoma and perioperative gastric carcinoma and NSCLC.