Still, most experts expressed optimism the partial hold will be removed and that the 200mg dose will advance.
On 25 July, the company announced the FDA had issued a partial clinical hold on Vertex’s ongoing Phase II US study of VX-135, a nucleotide (nuc) pyrimidine analogue. The agency’s decision prevents evaluation of the 200mg dose, following observation of reversible elevated liver enzymes in patients receiving 400mg VX-135 in combination with ribavirin in a Phase II study in Europe. Evaluation of a 100mg dose in combination with ribavirin in the 12-week Phase II US study is continuing as planned, according to the press release.
Vertex recently completed dosing of 100mg and 200mg VX-135 in combination with ribavirin in the 12-week Phase II European study, and both doses were well tolerated with no discontinuations. No serious adverse events (SAEs) have been reported and no liver or cardiac safety issues have been identified, according to the release. An adverse event is any undesirable experience associated with a medical product. The event is considered serious when the outcome is death, hospitalization, disability or permanent damage and/or congenital anomaly, among other important medical events, according to the FDA. Following completion of enrollment in the 100mg and 200mg arms of the European study, the study was amended to evaluate a 400mg dose in combination with ribavirin in 10 patients. Elevated liver enzymes were observed in three patients in this dose group, including one SAE, and the study’s 400mg arm was discontinued. After discontinuation, liver enzyme levels returned to baseline in all three patients, according to the same release.
