One of AbbVie’s most up-and-coming drugs faced a setback this week as the Food and Drug Administration placed a partial clinical hold on all the clinical trials testing it in a type of blood cancer.
The Chicago-based drugmaker said Tuesday that the FDA had placed the partial hold on trials of Venclexta (venetoclax) in multiple myeloma. The hold stems from a review of data from the Phase III BELLINI trial in relapsed/refractory disease, wherein the Venclexta arm showed a higher percentage of deaths than the control arm. Under the hold, no new patients can be enrolled in any studies of Venclexta in multiple myeloma until further analysis of the data is completed, AbbVie said.
Shares of AbbVie were down less than 1 percent following the news. Venclexta, a BCL-2 inhibitor that AbbVie markets with Roche’s Genentech division, was approved in 2016 for second-line chronic lymphocytic leukemia, or CLL, that harbors a mutation known as deletion 17p. Since then, its label has been expanded to include second-line CLL regardless of del-17p status, along with patients with acute myeloid leukemia who are at least 75 years old or have comorbidities that preclude the use of intensive induction chemotherapy.
Global sales of Venclexta were $344 million in 2018, more than double what they were in 2017, according to AbbVie. The company’s highest-selling hematological cancer drug is Imbruvica (ibrutinib), with global 2018 sales of $3.6 billion. Imbruvica is approved for CLL, mantle cell lymphoma, Waldenstrom’s macroglobulinemia and chronic graft-versus-host disease.
A pre-planned analysis of the data from BELLINI found that in the arm of patients receiving Venclexta with bortezomib and dexamethasone, 41 of 194 patients died, yielding a death rate of 21.1 percent. Of those, 13 deaths were treatment-emergent. By contrast, in the control arm, 11 of 97 deaths were observed, for a rate of 11.3 percent, with one death being treatment-emergent.
Of the 13 treatment-emergent deaths in the Venclexta arm, eight were judged to have resulted from infections, and more than half were in patients whose disease was refractory or progressive. On the other hand, the rates of severe and fatal toxicities, severe adverse events and infections were similar between both arms.
Venclexta had problems with toxicity early on in its development. In 2013 – when the drug went under the name ABT-199 – AbbVie suspended its development in CLL when a patient died from tumor lysis syndrome, or TLS, a metabolic disorder that sometimes occurs in hematological cancers and results from the rapid killing of large numbers of cancer cells whose contents are released into the blood. Still, the company managed to overcome the issue and resumed the drug’s development.
Photo: AbbVie
