FDA defies advisers; OK's AZ's ovarian cancer drug Lynparza
This article was originally published in Scrip
Even though the FDA's Oncologic Drugs Advisory Committee (ODAC) in June declined to back approval of AstraZeneca's Lynparza (olaparib), an oral inhibitor of polyadenosine 5-diphosphoribose polymerases, in ovarian cancer, the agency defied that advice and granted its blessing anyway on 19 December – although for a slightly different indication.
Shares of AstraZeneca closed at $71.69, down 42 cents.
The company gained European approval of Lynparza a day earlier (scripintelligence.com, 18 December 2014).
AstraZeneca had sought the FDA's nod to market Lynparza as a monotherapy for the maintenance treatment of adults with platinum-sensitive relapsed ovarian cancer, including fallopian tube or primary peritoneal, with germline BRCA mutation (gBRCAm) as detected by a companion diagnostic who are in complete response or partial response to platinum-based chemotherapy.
According to Lynparza's labeling, the drug is indicated as a monotherapy in patients with deleterious or suspected deleterious gBRCAm advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy.
The fourth-line indication, said RW Baird analyst Christopher Raymond, "seems more restrictive."
The ODAC had advised another study was needed to back up re-analyzed data from AstraZeneca's Phase II trial of the drug before regulators consider permitting the medicine to enter the US market (scripintelligence.com, 25 June 2014).
The committee of outside experts had voted 11-2 the safety and efficacy results of AstraZeneca's single trial, known as study 19, in patients with gBRCAm ovarian cancer were inadequate on their own to earn an accelerated approval and advised the agency to delay action on the investigational medicine until the company can show in a Phase III SOLO-2 confirmatory study.
The FDA had delayed its decision on Lynparza – extending the Prescription Drug User Fee Act action date from 3 October to 3 January 2015 – but that postponement was attributed a major amendment AstraZeneca submitted on 24 July to its new drug application for the drug.
Given the ODAC outcome and the fact that Phase III results are not expected until sometime next year, "few investors anticipated" Lynparza's approval.
Along with clearing Lynparza, the FDA also granted approval a companion diagnostic, BRACAnalysis CDx, which is based on a test made by Myriad Genetics.
Until now, the FDA said, the test was sold without the agency's approval as a laboratory developed test (LDT), which is a test that is designed, manufactured and used in a single laboratory.
The new test is approved as a companion diagnostic, specifically to identify patients with advanced ovarian cancer who may be candidates for treatment with Lynparza, the FDA said.
The BRACAnalysis CDx is the FDA's first approval of an LDT under a premarket approval application and is the first approval of an LDT companion diagnostic.
Second chance
AstraZeneca had actually abandoned Lynparza in 2011 after an interim analysis indicated the experimental medicine was unlikely to confer an overall survival benefit in serous ovarian cancer (scripintelligence.com, 20 December 2011).
But in 2012, a re-analysis of a subgroup of 96 patients with deleterious gBRCAm-associated platinum-sensitive ovarian cancer showed an 83% reduction in the risk of death and an 7.1 month median improvement in progression-free survival for patients who had been given Lynparza – 11.2 months for AstraZeneca's drug versus 4.1 months for the placebo arm.
Based on those results, the London drug maker decided to give Lynparza a second chance at life and revived the program – submitting an application to the FDA.
But the FDA raised concerns about the small sample size of gBRCAm patients and the retrospective identification of the patient population, which they said called into question the reliability of the estimation of treatment effect (scripintelligence.com, 23 June 2014).