Merck’s WINREVAIR Gets FDA Priority Review for Pulmonary Arterial Hypertension

Merck, also known as MSD outside the U.S. and Canada, announced that the FDA has accepted and granted Priority Review to the supplemental Biologics License Application (sBLA) for WINREVAIR (sotatercept-csrk). The application seeks to update the drug’s U.S. label based on findings from the Phase III ZENITH trial in pulmonary arterial hypertension (PAH, Group 1 PH). The FDA has set the Prescription Drug User Fee Act (PDUFA) action date for October 25, 2025.

In the ZENITH trial, WINREVAIR showed a 76% reduction in the risk of a composite of all-cause death, lung transplantation, or PAH-related hospitalization compared to placebo. The study was notably the first PAH Phase III trial to be stopped early by an independent data monitoring committee due to overwhelming efficacy. These findings were recently published in the New England Journal of Medicine.

“We are pleased that the FDA has accepted our sBLA and granted a Priority Review to include the impressive results of ZENITH,” said Dr. Joerg Koglin, Senior Vice President, Global Clinical Development, Merck Research Laboratories. “There remains a significant unmet medical need for patients living with PAH who, despite background therapy, remain at high risk.”

WINREVAIR was approved in 2024 for the treatment of adults with PAH to improve exercise capacity, WHO functional class, and reduce clinical worsening. It is currently approved in over 45 countries based on data from the STELLAR trial.

KalVista’s EKTERLY Approved by FDA as First Oral On-Demand HAE Treatment

KalVista Pharmaceuticals announced FDA approval of EKTERLY (sebetralstat), the first and only oral on-demand therapy for the treatment of acute hereditary angioedema (HAE) attacks in patients aged 12 years and older. This marks the first new on-demand HAE treatment approved in over a decade and offers a potentially transformative option for patients, particularly those burdened by injectable therapies.

“The FDA approval of EKTERLY is a defining moment for people living with HAE,” said Ben Palleiko, CEO of KalVista. “EKTERLY enables people to treat attacks the moment symptoms begin, wherever they are… EKTERLY has the potential to become the foundational treatment for HAE.”

Previously, all approved on-demand HAE treatments in the U.S. required intravenous or subcutaneous administration, often delaying response. EKTERLY, a plasma kallikrein inhibitor, offers a rapid, convenient oral option that may enhance treatment timing and patient independence.

“As the first orally administered on-demand therapy for HAE attacks, EKTERLY provides patients and physicians with an important and welcome advance,” said Anthony J. Castaldo, CEO of the U.S. Hereditary Angioedema Association.

Data from KalVista’s phase III KONFIDENT trial, the largest HAE trial to date—demonstrated EKTERLY’s rapid symptom relief, reduced severity, and favorable safety profile. The trial randomized 136 patients across 66 sites in 20 countries and showed a significantly faster response compared to placebo. These results were supported by the ongoing KONFIDENT-S extension study, in which patients reported treating attacks within a median of 10 minutes and consistent efficacy across all attack locations, including those involving the larynx.

“This is an important moment for patients,” said Dr. Marc A. Riedl, Professor of Medicine at UC San Diego. “Having an oral option empowers patients to treat early, aligning with current treatment goals.”

KalVista will begin the U.S. launch of EKTERLY immediately, supported by the KalVista Cares™ program offering access and reimbursement support.

FDA Grants Orphan Drug Status to Fujifilm’s FF-10832 for Biliary Tract Cancer

FUJIFILM Pharmaceuticals U.S.A., Inc. has announced that the FDA has granted orphan drug designation to FF-10832, an investigational liposomal formulation of gemcitabine, for the treatment of biliary tract cancer (BTC). FF-10832 is currently being evaluated in a phase IIa trial (NCT05318573) as monotherapy and in combination with pembrolizumab for solid tumors.

“BTCs are rare but aggressive malignancies associated with a poor prognosis and limited treatment options,” said Susumu Shimoyama, President of FUJIFILM Pharmaceuticals U.S.A., Inc. “Receiving orphan drug designation highlights the significant unmet medical need and supports the development of FF-10832 for patients who have few satisfactory options.”

With approximately 16,000 new BTC cases reported annually in the U.S., the majority are diagnosed at unresectable or metastatic stages, and existing therapies like surgery and chemotherapy offer limited efficacy. Gemcitabine remains a cornerstone of BTC treatment, and FF-10832’s liposomal formulation is designed to prolong plasma half-life and improve tumor targeting for enhanced anti-cancer activity.

The FDA’s orphan drug designation is intended to promote therapies for rare diseases, offering benefits like seven years of marketing exclusivity and potential financial incentives. Fujifilm’s CDMO capabilities, through FUJIFILM Toyama Chemical, ensure end-to-end development and manufacturing. The company also holds orphan drug designations for two other candidates—FF-10502 and FF-10850—for cholangiocarcinoma and Merkel cell carcinoma, respectively.

Mustang Bio’s MB-101 Receives FDA Orphan Drug Designation for Glioblastoma

Mustang Bio announced that the FDA has granted Orphan Drug Designation to its IL13Ra2-targeted CAR T-cell therapy, MB-101, for the treatment of recurrent diffuse and anaplastic astrocytomas and glioblastoma (GBM). This designation adds to the previously granted Orphan status for MB-108, Mustang’s HSV-1 oncolytic virus, reinforcing the company’s dual-therapy approach in difficult-to-treat brain cancers.

“We are thrilled that MB-101 received Orphan Drug Designation with a broader indication than initially proposed,” said Manuel Litchman, M.D., President and CEO of Mustang Bio. “This, along with MB-108’s designation, validates our science and highlights the potential of combining CAR T-cell therapy with an oncolytic virus to reshape the tumor microenvironment and improve outcomes for patients with malignant glioma.”

In a phase I trial conducted at City of Hope and published in Nature Medicine in 2024, MB-101 demonstrated encouraging clinical benefit, with 50% of patients achieving stable disease or better, including two complete responses lasting over 7.5 and 66+ months, respectively. These results were associated with tumors exhibiting high pre-treatment levels of CD3+ T cells, classified as “hot” tumors.

Preclinical data and findings presented at the 2022 AACR Annual Meeting support a combination strategy with MB-108 (oncolytic virus) and MB-101, aiming to convert immunologically “cold” tumors into “hot” ones to enhance CAR T-cell efficacy. Both MB-101 and MB-108 monotherapies were reported to be well-tolerated in clinical studies. Ongoing trials for MB-101 and MB-108 are continuing at City of Hope and the University of Alabama at Birmingham, respectively.

Mustang Bio stated that continued progress in its MB-109 program (MB-101 + MB-108) for GBM and high-grade astrocytomas will depend on securing additional funding or strategic partnerships.

Denali’s Tividenofusp Alfa Gets FDA Priority Review for Hunter Syndrome (MPS II)

Denali Therapeutics announced that the FDA has accepted and granted Priority Review to its Biologics License Application (BLA) for tividenofusp alfa, a next-generation enzyme replacement therapy for Hunter syndrome (MPS II). The agency has assigned a PDUFA target action date of January 5, 2026, as part of an accelerated approval pathway.

Tividenofusp alfa is engineered using Denali’s proprietary TransportVehicle™ platform to deliver the missing iduronate 2-sulfatase (IDS) enzyme both throughout the body and across the blood-brain barrier—a crucial advancement, given that existing therapies cannot reach the brain and fail to address the neurological symptoms of the disease.

“We are grateful to the FDA for their recognition of the urgent need for new therapies that could offer a significant improvement in the treatment of Hunter syndrome,” said Carole Ho, M.D., Chief Medical Officer and Head of Development at Denali. “If approved, tividenofusp alfa would be the first major advancement in nearly two decades for individuals living with this devastating disease, offering the potential to treat both cognitive and physical symptoms.”

The BLA is supported by results from an open-label phase I/II study involving 47 participants with Hunter syndrome, and the company is continuing its ongoing phase II/III COMPASS study to support global regulatory submissions. Denali is also actively preparing for a potential commercial launch in the U.S. while continuing to expand its TransportVehicle-enabled pipeline targeting lysosomal storage diseases and neurodegenerative conditions.