FDASIA’s Innovation Component

Jan. 3, 2014
Oncology Business Unit Head Kevin Lokay discusses Boehringer Ingelheim’s Breakthrough Therapy designation for an advanced development-stage cancer treatment

PhM: Congratulations on receiving a Breakthrough Therapy designation for Volasertib, Boehringer Ingelheim’s investigational drug for treating acute myeloid leukemia.

Kevin Lokay: “Volasertib is one of several late-stage compounds that Boehringer Ingelheim is evaluating in clinical trials for various solid tumors and hematological cancers. Volasertib is an investigational inhibitor of polo-like kinase, an enzyme in the Plk family that regulates cell division. This inhibition is intended to result in prolonged cell cycle arrest, ultimately leading to cell death, or apoptosis. Volasertib is under evaluation for the treatment of patients aged 65 or older with previously untreated acute myeloid leukemia (AML), who are ineligible for intensive remission induction therapy. AML is an aggressive cancer of the bone marrow and blood. It accounts for 25 percent of all adult leukemias in the Western world and has one of the lowest survival rates of all leukemias.”

PhM: Breakdown for us please how the Breakthrough Therapy designation was realized.

KL: “The Breakthrough Therapy designation for Volasertib is based on Phase II clinical findings observed to date. Data from the Phase II part of a Phase I/II study were presented at the 54th American Society of Hematology (ASH) annual in December 2012. As of Sept. 30, 2013, 29 investigational drugs have received Breakthrough Therapy designation. At this time, Boehringer Ingelheim is unaware of any other Breakthrough Therapy designation in this AML treatment setting.”

PhM: What does the designation mean for sponsors?

KL: “The innovation provisions of FDA’s Safety and Innovation Act (FDASIA) and Breakthrough Therapy designation allow the FDA to work collectively with pharma companies to expedite the development, review and availability of important new treatments. The designation status has begun to change the way the FDA and the industry prioritize drug development, but understanding the significance of its impact on timing and influence in the health system will take more time. We look forward to working closely with the FDA on the development of Volasertib.”

PhM: What are some differences between Breakthrough and Fast Track designations?

KL: “Breakthrough Therapy and Fast Track designation programs are similar because they both are intended to expedite the development and review of drugs for serious or life-threatening conditions. The differences lie in what needs to be demonstrated to qualify for each program. A Breakthrough Therapy program is for a drug that treats a serious or life-threatening condition, and for which preliminary clinical evidence indicates that the drug may demonstrate substantial improvement on a clinically significant endpoint(s) over available therapies. By contrast, a Fast Track program is for a drug that treats a serious/life-threatening condition, but where nonclinical or clinical data demonstrate the potential to address unmet medical need.”

PhM: What is the expected clinical development timeline for Volasertib? Can you compare that to a more conventional approval and development pathway?

KL: Volasertib recently advanced into Phase III clinical development for treating patients with AML. The Phase III trial, known as POLO-AML-2 (Clinical Trial Identifier: NCT01721876), is a randomized, double-blind study designed to assess the efficacy and safety of Volasertib in combination with low-dose cytarabine (LDAC), compared to placebo in combination with LDAC, as a potential treatment for patients aged 65 or older with previously untreated AML who are ineligible for intensive remission induction therapy. The trial began in early 2013 and is expected to end in April 2016.

Traditionally, drug reviews occur through a series of scheduled meetings, but with the Breakthrough Therapy designation the company and FDA speak more frequently. The process also involves FDA senior management, not just FDA reviewers. This provides Boehringer Ingelheim the opportunity to engage in an ongoing dialogue with a dedicated, senior FDA management team, which will help to expedite the development and review of volasertib. Boehringer Ingelheim will work closely with FDA to determine the most efficient path forward for developing Volasertib.