Roche’s Venclexta Granted Full Approval Under Project Orbis and Real-Time Review


The U.S. Food and Drug Administration (FDA) granted Roche’s Venclexta (venetoclax) full approval in combination with azacytidine, or decitabine, or low-dose cytarabine (LDAC) for newly diagnosed acute myeloid leukemia (AML) in adults 75 years or older. It is also approved for use in patients with comorbidities that prevent them from receiving intensive induction chemotherapy.

The drug had received provisional approval for this indication under the agency’s accelerated approval program in November 2018. This announcement converts the accelerated approval to a full approval.

“Today’s full approval is supported by the significant results that showed that Venclexta in combination with azacytidine extended overall survival for people with newly diagnosed acute myeloid leukemia who cannot tolerate intensive induction chemotherapy,” said Levi Garraway, Roche’s chief medical officer and head of Global Product Development. “We are very pleased that this application was reviewed under the FDA’s Real-Time Oncology Review pilot and Project Orbis initiative, helping to bring this treatment option more rapidly to patients in the United States and other countries.”

The Real-Time Oncology Review (RTOR) Pilot has a goal of exploring a more efficient review process to make safe and effective cancer treatments available to patients as early as possible. For the pilot program, New Drug Application (NDA) and Biologics License Application (BLA) submissions are chosen from each clinical division to determine the feasibility and to optimize the process for RTOR. Submissions in the program have to meet several criteria, including drugs likely to show substantial improvements over current therapies, straightforward study designs, and easily interpreted endpoints.

The FDA’s Project Orbis offers a framework for concurrent submission and review of oncology therapies among international regulators. These partners include Australia’s Therapeutic Goods Administration, Health Canada, the European Medicines Agency, Japan’s Pharmaceuticals and Medical Devices Agency, and Switzerland’s Swissmedic. The FDA and China’s National Medical Products Administration have begun quarterly discussions over non-product specific regulatory issues.

Simultaneous applications were submitted to U.S., Australia, Canada, Brazil and Switzerland regulators under Project Orbis. Venclexta has also received five Breakthrough Therapy Designations from the FDA, two of which were for patients with previously untreated AML ineligible for intensive chemotherapy.

The full approval was primarily based on data from two Phase III trials, VIALE-A and VIALE-C. VIALE-A demonstrated Venclexta plus azacytidine significantly decreased the risk of death by 34%. Patients treated with the drug plus azacytidine had significantly higher rates of complete remission with 37% compared to 18% in people receiving only azacytidine.

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In the VIALE-C trial, 27% of people receiving Venclexta plus LDAC hit a complete remission compared to 7.4% of people with LDAC alone. The median overall survival for people receiving the combination was 7.2 months compared to 4.1 months for LDAC alone. The overall survival data were not statistically significant.

“The results of the VIALE-A study reinforce the clinically meaningful benefit of Venclexta plus azacytidine for people newly diagnosed with AML,” said Courtney DiNardo, associate professor of the Department of Leukemia, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center. “Based on the results of this study, this treatment regimen represents a significant advance for older AML patients, including higher response rates, greater transfusion independence, longer durations of remission, and ultimately significantly improved overall survival compared to azacytidine alone.”

Venclexta is a first-in-class targeted drug that selectively binds and inhibits the B-cell lymphoma-2 (BCL-2) protein. In some blood cancers and other tumors, BLC-2 accumulates and prevents cancer cells from dying or self-destructing, called apoptosis. Venclexta inhibits the BCL-2 protein and helps restore apoptosis.


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