FDA Lifts Partial Hold on AbbVie Phase III Study for MM

The U.S. Food and Drug Administration (FDA) lifted a partial clinical hold placed on AbbVie’s Phase III CANOVA trial evaluating venetoclax for the treatment of relapsed/refractory multiple myeloma, the company announced this morning.

The CANOVA trial evaluates venetoclax in combination with dexamethasone versus pomalidomide in combination with dexamethasone in patients with relapsed/refractory multiple myeloma positive for the translocation abnormality. The genetic biomarker is among the most common and routinely tested genetic abnormalities in patients with multiple myeloma.

Illinois-based AbbVie said the FDA lifted the hold based upon agreement on revisions to the CANOVA study protocol. Those revisions include new risk mitigation measures, protocol-specified guidelines and updated futility criteria. Enrollment in the CANOVA trial may resume as determined by each participant site based on the approved protocol, AbbVie announced today.

“We are pleased to move forward with the CANOVA study which, with the t biomarker test, can help identify patients who may respond better to treatment and add clarity for physicians when choosing a therapy, if approved,” Mohamed Zaki, global head of hematology development at AbbVie said in a statement. “We are working closely with regulatory authorities worldwide to continue our efforts to understand the potential of venetoclax for patients with multiple myeloma while continuing to advance research in patients with the t genetic abnormality.”

The FDA placed the partial hold in March on all trials evaluating Venclexta (venetoclax) for the investigational treatment of multiple myeloma. AbbVie said all other trials evaluating venetoclax in patients with multiple myeloma remain on partial clinical hold while next steps continue to be evaluated with the agency. When the partial clinical hold was placed in March, AbbVie said the decision followed a review of data from the ongoing Phase III BELLINI trial, another multiple myeloma study. In the BELLINI trial, AbbVie said a higher proportion of deaths was observed in the venetoclax arm compared to the control arm. As BioSpace reported at the time, 41 of the 194 patients who were on the venetoclax arm of the trial died. Of those, 13 were considered treatment emergent, meaning the events were not present prior to medical treatment. Of the 13 treatment-emergent deaths in the venetoclax arm, AbbVie said eight were attributed by the investigator to an event of infection, and more than half were in the setting of refractory or progressive disease. There were 11 patients on the placebo arm that died during the course of the trial.

Results from the Phase III BELLINI trial were presented at the 24th European Hematology Association Annual Congress earlier this month. The BELLINI trial met its primary endpoint of improved progression-free survival and demonstrated statistically significant improvement in overall response. Safety analyses showed the majority of deaths in the venetoclax arm were related to infection and progressive disease. Additional data will be presented at a future congress or published in a medical journal, the company said.

Venetoclax, which is sold as Venclexta and Venclycto, is not approved by any regulatory authority, in any country for the treatment of multiple myeloma. In November, Venclexta was approved for the treatment of newly-diagnosed acute myeloid leukemia in adults who are age 75 years or older or who cannot tolerate intensive chemotherapy. The drug has also been approved for certain patients who have been diagnosed with chronic lymphocytic leukemia and small lymphocytic lymphoma. Venetoclax is being developed by AbbVie and Roche’s subsidiary, Genentech.