Scynexis has resumed dosing of its vaginal yeast infection drug Brexafemme (ibrexafungerp) in a Phase III trial after a 19-month clinical hold by the US Food and Drug Administration (FDA).
The resumption of dosing in the MARIO study (NCT05178862) comes after the FDA lifted the clinical hold last month, originally in place due to concerns about cross-contamination. Scynexis said the investigational sites were reactivated a few days ago, as per a 28 May press release.
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The issue was highlighted after a review from GSK, which signed a licensing deal for the drug with Scynexis in 2023. The British big pharma noted that the manufacturing site for Brexafemme also produced a non-antibiotic beta-lactam substance.
This drug, which can cause allergic reactions in some patients, has been the subject of an FDA draft guidance that details the separation of manufacturing processes for these compounds. In September 2023, Scynexis issued a voluntary recall of Brexafemme, an FDA-approved treatment for vulvovaginal candidiasis (VVC), due to the potential for cross-contamination.
Scynexis said the study has resumed following the manufacture of new clinical supplies at another site.
The Phase III MARIO study is investigating oral Brexafemme as a potential step-down antifungal therapy following intravenous (IV) echinocandin for invasive candidiasis, a potentially life-threatening infection. The trial has enrolled around 25% of its 220-patient target.
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By GlobalData“We are pleased to announce the dosing of the first new patient in the Phase III MARIO study following the lifting of the clinical hold by the FDA in April,” said Scynexis CEO David Angulo.
“The rapid resumption of patient enrolment, just a few days after the investigational sites were reactivated in the study, reflects the eagerness of the scientific community to have new treatment options for this life-threatening infection.”
MARIO being back on track comes amid a saga between Scynexis and GSK, with the companies pointing fingers at each other with regard to trial duties.
During its Q1 earnings report, Scynexis said that GSK had tried to terminate the study, with Angulo affirming plans to move forward with Brexafemme in this new indication.
There used to be substantial cash on the line. The partnership in 2023 included not just a $90m upfront payment, but up to $503m in milestone payments. However, after the commercial delays, millstone payments were cut in a revised deal in December 2023. Approval-based milestones were slashed from $70m to $49m, whilst commercial counterparts were halved from $115m to a potential $57.5m. Milestone payments based on sales were also downwardly revised. By dosing the first new patient, Scynexis believes it has now triggered a $10m payment, with another $20m to arrive by the six-month anniversary of dosing.
“As previously disclosed, there is a disagreement between Scynexis and GSK regarding the resumption of the MARIO Study and GSK’s responsibility for paying these milestones. Scynexis is working to resolve the disagreement,” Scynexis said in a statement.
GSK did not immediately respond to Pharmaceutical Technology’s request for comment.
Scynexis reported $3.7m in revenue for 2024, which primarily consisted of the licence agreement with GSK. Brexafemme generated sales of $5m in 2022 before the recall. GlobalData’s Pharma Intelligence Center forecasts global sales of $139m by 2031, a valuation that hinges on the outcome of the MARIO study and a subsequent label expansion.
GlobalData is the parent company of Pharmaceutical Technology.
