GSK and Scynexis Clash Over Milestone Payments as Brexafemme Trial Resumes

Clinical Hold Lifted on Antifungal Drug Brexafemme

The U.S. Food and Drug Administration (FDA) has lifted its clinical hold on Brexafemme (ibrexafungerp), a vaginal yeast infection drug developed by Scynexis and licensed to GSK. This decision comes after a 19-month delay, allowing the resumption of the phase 3 MARIO study investigating Brexafemme as a potential step-down treatment for invasive candidiasis.

Scynexis announced that it has dosed the first new patient in the MARIO trial, marking a significant milestone in the drug's development. Dr. Luis Ostrosky-Zeichner, a professor at UTHealth Houston, emphasized the urgent need for new treatments in this area, stating, "There is substantial need for new treatments for invasive candidiasis, particularly for Candida strains resistant to the currently approved antifungals."

Dispute Erupts Over Milestone Payments

The trial resumption has triggered a disagreement between Scynexis and GSK regarding milestone payments. Scynexis claims that the dosing of the first new patient activates a $10 million milestone payment from GSK, with an additional $20 million due in six months. However, GSK is contesting these charges.

David Angulo, M.D., CEO of Scynexis, revealed that GSK had expressed reluctance to resume the trial after the prolonged delay. Despite this, Scynexis stated it is working with GSK to "resolve the disagreement."

A GSK spokesperson reiterated the company's commitment to the partnership, saying, "We continue to work with Scynexis to commercialize Brexafemme. With rates of resistance to other antifungal treatments rising, Brexafemme addresses a clear unmet need for new oral treatments and is an important asset of our growing anti-infectives portfolio."

Brexafemme's Journey and Partnership Challenges

Brexafemme has had a complex development and commercialization history. The FDA initially approved the drug in 2021 for vulvovaginal candidiasis (VVC), commonly known as yeast infection. In 2022, it received an additional approval to reduce the risk of recurrent VVC.

GSK entered into a partnership with Scynexis in 2023, paying $90 million upfront with the potential for up to $503 million in milestone payments. However, the relationship faced challenges when GSK discovered that the equipment used to produce Brexafemme was also used to manufacture a beta-lactam substance, which can cause allergic reactions in some individuals.

This discovery led to a voluntary recall of Brexafemme tablets in September 2023 due to potential cross-contamination, resulting in the MARIO trial being put on hold. The recent lifting of the clinical hold and the resumption of the trial mark a significant turning point in the drug's development trajectory.

As the pharmaceutical industry closely watches the outcome of this dispute and the progress of the MARIO trial, the future of Brexafemme and the partnership between GSK and Scynexis remains uncertain. The resolution of the milestone payment disagreement and the successful completion of the phase 3 study will be crucial factors in determining the drug's potential to address the growing need for new antifungal treatments.