FDA Puts Partial Hold on Venetoclax’s Multiple Myeloma Trials

The U.S. Food and Drug Administration (FDA) has placed a partial clinical hold on venetoclax’s multiple myeloma trials after new safety concerns were raised during a review of the BELLINI Phase 3 trial (NCT02755597).

This means that all ongoing clinical trials assessing AbbVie‘s venetoclax in multiple myeloma can no longer enroll or dose new patients until a full analysis is completed to clarify the potential safety concerns. Patients already receiving the therapy and benefiting from it may continue the treatment after consulting with their physician.

Researchers recommend that multiple myeloma patients taking venetoclax speak immediately with their doctor to decide the best and safest way to proceed. For medical-related questions, please call Abbott Medical Information at 1-800-633-9110.

The setback is only applicable to the myeloma clinical program, having no impact on any other approved indications for venetoclax.

“We will continue to further the research and development of venetoclax and other therapies with the potential to transform the standards of care in blood cancers,” Michael Severino, MD, vice chairman and president of AbbVie, said in a press release.

BELLINI was designed to assess the safety and activity of venetoclax in combination with standard Velcade (bortezomib) and dexamethasone in relapsed or refractory myeloma patients.

The study, conducted across 97 clinical sites worldwide, enrolled 291 patients who had received one to three prior lines of therapy and were sensitive to or had not been treated with proteasome inhibitors, such as Velcade.

The trial’s main goal was to determine whether venetoclax could delay disease progression or death when added to standard of care, which it did. Patients receiving the triple combination lived without signs of disease worsening for 22.4 months versus 11.5 months for those receiving Velcade plus dexamethasone only. This represents a 37% reduction in the risk of disease progression or death.

Overall responses and very good partial responses were also better among those receiving venetoclax, researchers reported.

However, while the incidence of serious adverse events was similar between the two groups, a pre-planned safety analysis showed twice as many deaths in the venetoclax group — 41 out of 194 patients (21.1%) — than in the control group — 11 out of 97 (11.3%).

Among the 41 deaths in the venetoclax arm, 6.7% were deemed treatment emergent, and most often caused by an infection. Treatment-emergent deaths occurred in 1% of patients in the control arm.

“We are committed to patient safety and are thoroughly analyzing the results observed in the BELLINI trial,” Severino said. “We will continue working with the FDA and worldwide regulatory agencies to determine appropriate next steps for the multiple myeloma program.”

Venetoclax is an orally available BCL-2 inhibitor that aims to unblock the cell death pathway in tumor cells. The approach triggers natural death mechanisms and allows cancer cells to die naturally, as they should in normal circumstances.

The inhibitor is being jointly developed by AbbVie and Roche for the treatment of several blood and solid tumors. It is approved in more than 50 countries, with the brand names Venclexta and Venclyxto, for the treatment of some patients with chronic lymphocytic leukemia or small lymphocytic lymphoma, and acute myeloid leukemia.