FDA lifts hold on AbbVie, Roche's Venclexta in myeloma after drugmakers pledge risk remedies

After a spate of trial deaths forced AbbVie and Roche to halt trial enrollment for oncology med Venclexta in multiple myeloma, the future seemed dim for the drug’s expansion hopes in the disease. But now, after taking steps to increase safety, the drugmakers are getting another shot.

The FDA lifted its partial clinical hold on Venclexta’s phase 3 trial for relapsed multiple myeloma patients who test positive for a specific biomarker after AbbVie and Roche agreed to put new risk mitigation measures in place, update the study’s futility criteria and add protocol-specific guidelines for patient treatment, AbbVie said.

The lifted hold only applies to one study, dubbed Canova, with additional multiple myeloma trials still barred from enrolling new patients. Other Venclexta studies in approved indications such as chronic lymphocytic leukemia (CLL) and acute myeloid leukemia had not been placed on hold, AbbVie said.

"We are working closely with regulatory authorities worldwide to continue our efforts to understand the potential of (Venxclexta) for patients with multiple myeloma while continuing to advance research in patients with the t(11;14) genetic abnormality." Mohamed Zaki, AbbVie’s hematology head, said in a statement.

The FDA’s limited decision follows a troubled three months for the med after a series of deaths in a Venclexta phase 3 multiple myeloma trial, called Bellini 3, halted new enrollment and threatened to end the program altogether. According to an interim survival analysis, a combination of Venclexta, Takeda proteasome inhibitor Velcade and dexamethasone nearly doubled the risk of death over placebo, with 41 of 194 patients in the experimental arm dying. By contrast, 11 of 97 patients on placebo died in the same span.

Venclexta, touted as part of AbbVie’s answer to a growing suite of generic challengers to its legacy blockbuster Humira, had largely breezed through the trial phase in its two approved indications but joined other major drugmakers in facing trouble in myeloma.

In 2017, Merck halted enrollment on a pair of phase 3 Keytruda studies in the disease after trial deaths prompted concerns about the drug’s dosing alongside Celgene’s Revlimid and Pomalyst. The FDA eventually put two trials on full hold and stopped dosing in a third, with all patients discontinuing treatment.

Despite its multiple myeloma troubles, Venclexta has had more recent success in CLL after the FDA approved the drug in May as a combo therapy with Roche’s Gazvya for previously untreated patients. AbbVie rolled out the underlying data for that approval earlier this month, showing the Venclexta-Gazvya combo cut the risk of disease progression by 65% over a standard-of-care combo of Gazvya and chlorambucil.