Astra’s Lynparza becomes first Parp inhibitor
Neither a negative panel vote nor an application based on a subgroup analysis from a failed trial has put the FDA off granting approval for AstraZeneca’s Lynparza for ovarian cancer – and granting it early. Thanks to a European approval the day before the drug has become the first Parp inhibitor to reach the market, and has done so worldwide.
Two phase III studies are still ongoing, and if no survival benefit is seen the drug could yet be pulled. But, narrow though the indication is, the approval is a fillip for Astra. It is also a victory for Myriad Genetics, whose embattled BRACAnalysis homebrew test got the nod as a companion diagnostic, marking the first time that the FDA had approved such a product.
Parp the herald angels sing
The approval validates Astra’s decision to resurrect Lynparza, aka olaparib, following the crashing of the Study 19 trial in a broad base of ovarian cancer patients in 2011 (Parp field hots up as AstraZeneca puts second contender into phase III, September 4, 2013). The drug can now be used in heavily pretreated patients with advanced ovarian cancer who have deleterious mutations in the BRCA1 and BRCA2 genes.
Astra must hope that Lynparza’s swift approval and first-in-class status mean sales will be at the top end of analysts’ forecasts, which according to EvaluatePharma could, if Astra is very lucky, see it become a blockbuster by 2020.
The accelerated approval means the drug is still, in a sense, under evaluation. The ongoing phase III trials must demonstrate a benefit for Lynparza on overall survival – something that no ovarian cancer drug has yet shown – in the niche patient group at which it is aimed (Therapeutic focus – Survival benefit still eludes ovarian cancer trials, November 12, 2014).
Joyful and triumphant?
The product used to determine whether a patient might respond to Lynparza will be BRACAnalysis CDx. This test has been sold in the US as BRACAnalysis for over 10 years, but under a quirk of the US regulatory system it has not, until now, been approved by the FDA. Instead it has been sold as a so-called lab-developed test: the facilities at which the test is performed are certified by the Centers for Medicare & Medicaid Services, but no FDA oversight is required.
Lynparza's European approval covers patients with platinum-sensitive relapsed BRCA-mutated ovarian cancer, and therefore a test for BRCA status will also be required. BRACAnalysis will be available in Europe, Myriad said, but it is not known if other tests may be used here.
As for the US, the FDA said that this was the first time a lab-developed, or homebrew, test had gained formal premarket approval. The move is a strategy change for Myriad, which has hitherto been happy to sell BRACAnalysis to women who wish to find out their risk of developing cancer without troubling the FDA.
The FDA stated that approval of BRACAnalysis CDx was based on data from the same clinical trial used to support approval of Lynparza; blood samples from trial participants were tested to validate BRACAnalysis CDx’s use for detecting BRCA mutations in this population.
Presumably the agency means that that patients were tested independently, using another method, to determine their BRCA status before treatment with Lynparza. These BRCA status results must have then compared with those obtained with BRCAnalysis CDx.
In any case, the approval means that Myriad has secured a place for BRACAnalysis on the US market after losing, in June last year, the exclusivity as a BRCA test it had long claimed. Last week, an attempt by Myriad to force a lab-developed BRCA test from Ambry Genetics off the market failed.
The approval therefore means that, while Myriad is still not the monopoly it once was, its product has, like Lynparza, become the first of its kind to gain FDA approval.
|Ongoing phase III Lynparza trials|
|Phase III trial of Lynparza in 2,500 patients with ovarian cancer||NCT01844986|
|Phase III trial of Lynparza in 440 patients with ovarian cancer||NCT01874353|