AstraZeneca faces olaparib questions
pharmafile | June 24, 2014 | News story | Manufacturing and Production, Research and Development, Sales and Marketing | AstraZeneca, Cancer, FDA, olaparib, ovarian
AstraZeneca is facing questions from US regulators over the efficacy of one of its most promising late-stage treatments.
Olaparib is a potential first-in-class oral poly ADP ribose polymerase (PARP) inhibitor for ovarian cancer and is expected to reach peak annual sales of around $1.5 billion.
However, the drug has had a difficult journey – AstraZeneca came close to ditching it completely in 2011 after it performed poorly in several trials – and it is far from on the market yet.
The manufacturer’s new drug application is for olaparib capsules as monotherapy for ovarian cancer patients with germline BRCA mutation (gBRCAm), who are in complete or partial response to platinum-based chemotherapy.
But questions raised before the US Food and Drug Administration’s Oncology Drug Advisory Committee meeting this week cast doubt on whether its risk-benefit profile is favourable.
The committee was also considering whether some impressive trial results – namely, the 83% reduction in the risk of progression or death and a seven-month median improvement in maintenance progression-free survival – could be relied upon.
“There are uncertainties related to the validity and the reproducibility of the magnitude of effect seen in Study 19, and there are risks associated with olaparib therapy,” an internal FDA document ran.
The committee will therefore vote on whether to grant accelerated approval for the drug now or wait until the results of the Phase III SOLO-2 study are available.
It will also discuss exactly what treatment effect – taking into account median improvement and hazard ratio – SOLO-2 will need to demonstrate before the FDA considers olaparib “to be of direct clinical benefit”.
The FDA does not have to follow its committees’ advice, although the regulator tends to.
Since the proposed indication is for maintenance treatment of patients who have just completed a course of cytotoxic chemotherapy “and are expected to receive multiple treatment regimens throughout their lives, tolerability and cumulative toxicities are paramount issues”, the FDA insists.
If it is successful olaparib, originally developed by Targacept, is coming into a therapy area beset by previous failures, and stiff competition in the form of Roche’s Avastin (bevacizumab).
Adam Hill
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