Venclexta Combo Continues to Help Untreated AML Patients in Phase 3 Trial

Venclexta Combo Continues to Help Untreated AML Patients in Phase 3 Trial

When given alongside Vidaza (azacitidine), Venclexta (venetoclax) elicits clinically meaningful responses and prolongs survival in untreated acute myeloid leukemia (AML) patients who are not eligible for intense chemotherapy, a Phase 3 confirmatory trial shows.

These findings were in the late-breaking oral presentation “A Randomized, double-blind, placebo-controlled study of venetoclax with azacitidine vs azacitidine in treatment- naive patients with acute myeloid leukemia ineligible for intense therapy-VIALE-A,” given at the recent 25th European Hematology Association (EHA) Virtual Congress.

Venclexta, marketed as Venclyxto in Europe, is an oral small molecule developed and marketed by Genentech, a Roche subsidiary, and AbbVie. It is approved in the U.S. to treat different types of cancer, including AML in patients 75 or older who do not qualify for standard chemotherapy.

The therapy works by blocking the activity of a protein, called B-cell lymphoma-2 (BCL-2), that normally protects cells from being destroyed. By preventing cancer cells from over-producing this protein, Venclexta primes them for programmed cell death (apoptosis).

A Phase 3 trial called VIALE-A (NCT02993523) is currently investigating the safety and efficacy of Venclexta, when given with Vidaza, in AML patients who never received any form of treatment and are not eligible for intense chemotherapy.

The study enrolled 433 adults randomly assigned to either Venclexta in combination with Vidaza, or Vidaza plus a placebo.

Interim study data, announced by AbbVie earlier this year, indicated the Venclexta-Vidaza combination therapy significantly extended survival when compared to Vidaza alone. In addition, those given the combination seemed to respond better to treatment than those given Vidaza.

Detailed data now announced by Roche showed that at a median follow-up of 20.5 months, the combination therapy prolonged the time patients lived to a median of 14.7 months from 9.6 months, reducing the risk of death by 34% compared to Vidaza alone.

Venclexta plus Vidaza also increased the percentage of patients attaining complete remission, meaning those not showing any signs of cancer, compared to Vidaza alone (66.4% versus 28.3%).

Its safety profile was consistent with that of both medications when used separately. No new unexpected safety concerns were identified during the study.

The most common serious adverse events observed in both treatment groups included low platelet counts, low white blood cell counts, low white blood cell count with fever (febrile neutropenia), and anemia.

“We are very pleased to present these important results from people with acute myeloid leukaemia, especially those who are unable to tolerate intensive chemotherapy and therefore have limited treatment options,” Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Roche, said in the press release.

“The significant survival benefits observed in the VIALE-A study reinforce the potential utility of this Venclexta/Venclyxto-based combination for people with this aggressive disease,” Garraway said.

These latest VIALE-A data were shared with regulatory authorities worldwide, including the U.S. Food and Drug Administration (FDA), Roche also stated. They are expected to support the combination for full approval, required under the accelerated approval granted in 2018 for newly diagnosed AML patients who aren’t eligible for standard chemotherapy, either because they have particular health conditions or because they are over 75 years old.

In addition to VIALE-A, another confirmatory trial called VIALE-C (NCT03069352) is underway.