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Pink Sheet – Real-Time Oncology Review Quickly Grows Popular; Venclexta Is Latest To Join Pilot

Pink Sheet – Real-Time Oncology Review Quickly Grows Popular; Venclexta Is Latest To Join Pilot

Executive Summary

Genentech/AbbVie drug becomes the seventh product known to be pilot-testing US FDA’s new pathway; our infographic details the program’s goals and how it has been used so far for more efficient reviews of supplemental oncology indications.


Genentech Inc. is at the forefront of sponsors vying to use the US FDA Oncology Center of Excellence’s Real-Time Oncology Review (RTOR) pilot program, as the Roche subsidiary announced a second application being reviewed under the speedy new pathway.


A supplemental new drug application (sNDA) for a new indication for Venclexta (venetoclax) – use in combination with Gazyva (obinutuzumab) in people with previously untreated chronic lymphocytic leukemia (CLL) and co-existing medical conditions – is being evaluated under the RTOR pilot, which allows sponsors to share pivotal trial data with FDA prior to formal submission of an application.


Genentech and its Venclexta partner AbbVie Inc. announced the use of the RTOR, as well as a new breakthrough therapy designation (BTD) for Venclexta in the same indication, on March 7, 2019.


A month ago, Genentech announced an sBLA submission under the RTOR pilot for the antibody-drug conjugate Kadcyla (ado-trastuzumab emtansine) for adjuvant treatment of patients with HER2-positive early breast cancer with residual disease after neoadjuvant treatment. (Also see “Keeping Track: CDER Approves Its First Two Novel Agents Of 2019” – Pink Sheet, 10 Feb, 2019.)


The RTOR pilot program kicked off mid-2018 after it was unveiled by FDA Commissioner Scott Gottlieb at the American Society of Clinical Oncology annual meeting. (Also see “Gottlieb Uses ASCO Platform To Unveil Two Pilot Programs To Speed Drug Review” – Pink Sheet, 3 Jun, 2018.)


The pilot focuses on cancer therapies that appear likely to demonstrate substantial improvement over available therapy – a standard similar to that for breakthrough therapy designation – and have straightforward study designs and endpoints that can be easily interpreted.


Uptake of the program has been swift: four RTOR applications have been approved, with three more under review and at least one in the presubmission phase, according to the Pink Sheet FDA Performance Tracker. (See chart at end of story).


The ability to start on key data analyses before a formal submission has functionally “left-shifted the review clock,” as Office of Hematology & Oncology Products Acting Deputy Director Gideon Blumenthal described it to the Friends of Cancer Research annual meeting. PS124325


As a result, approvals have been issued remarkably fast. Seattle Genetics’ Adcetris (brentuximab vedotin), for example, was approved 11 days after the application for previously untreated CD30-expressing peripheral T-cell lymphomas was submitted.

Joint Real-Time And Breakthrough Announcements May Be Trend

The Venclexta sNDA will also benefit from the “all-hands-on-deck” approach to reviews of products holding a breakthrough therapy designation (BTD). The BTD is based results of the same trial supporting the sNDA, the Phase III CLL14 trial conducted in cooperation with the German CLL Study Group. It is the fifth BTD awarded to Venclexta.


A joint BTD/RTOR announcement is emerging as a potential theme for the pilot program. BTDs were also announced along with recent RTOR announcements for Genentech’s Kadcyla and Seattle Genetics’ Adcetris.


Data from the CLL14 trial in previously untreated CLL patients with co-existing medical conditions will be presented at an upcoming medical meeting, Genentech said. “CLL14 is the first randomized trial in CLL to examine a chemotherapy-free, fixed-duration treatment regimen,” AbbVie noted.


The trial Phase III trial randomized 432 patients to either a fixed-duration combination of 12 months of Venclexta alongside six months of Gazyva, or to the comparator arm of six months of Gazyva alongside 12 months chlorambucil for six months. The study met its primary endpoint, investigator-assessed progression-free survival (PFS), Genentech reported, showing a statistically significant reduction in the risk of disease worsening or death compared to standard-of-care Gazyva plus chlorambucil.


“No new safety signals were identified with the combination,” Genentech said.


Venclexta is currently indicated for patients with CLL or small lymphocytic leukemia, with or without 17p deletion, who have received at least one prior treatment and in combination with azacitadine, decitabine or low-dose cytarabine for newly-diagnosed acute myeloid leukemia (AML) in patients who are elderly or have other medical conditions that prevent use of standard chemotherapy.…