Back in 2012, olaparib was just another train wreck for AstraZeneca; a Phase II failure in ovarian cancer that was wrapped up and put on the shelf, forcing the pharma giant to write off $285 million. Today, AstraZeneca ($AZN) reversed that big charge-off after dosing the first patient in a Phase III trial inspired by a retrospective analysis of the mid-stage data--a high-stakes gamble that the PARP inhibitor will benefit a large portion of the patient population with a BRCA mutation.
For AstraZeneca's CEO Pascal Soriot, who's trying to convince analysts he can turn this troubled ship around, it's a chance to chalk up another desperately needed Phase III program in a crucial disease arena. But it's also shining a spotlight on the company's second take of old data--with a highly risky approach to pushing ahead on a drug that has a dubious claim on efficacy.
Last summer at the big ASCO meeting in Chicago, investigators laid out their best case for the drug. After seeing tantalizing signs of a more distinct patient response among the minority of 265 platinum-sensitive, relapsed, previously treated ovarian cancer patients they knew had a BRCA mutation, they went back and identified all the BRCA mutation patients in the trial. It was just over half. And in that half they found a progression-free survival rate of 11.2 months for the olaparib arm and 4.3 months in the placebo group. That's very good. But there's an important caveat. The overall survival in the olaparib arm was 34.9 months compared to 31.9 months for placebo. That was not statistically significant, but the researchers say that the placebo arm "subsequently received a PARP inhibitor," which may have skewed the data.
That's not a great way to distinguish a cancer drug. But as Datamonitor Healthcare analyst Joseph Hedden recently noted, though, AstraZeneca is focusing on PFS in Phase III, looking for an approval to use the drug as a maintenance therapy for patients demonstrating remission following chemo. Once the disease progresses following olaparib, the patient could go back to a platinum-based therapy, making it hard to track any significant OS data. Significant PFS results could generate an approval, he added.
There's another consideration: While AstraZeneca has inked a slate of early-stage cancer deals, its late-stage oncology pipeline is lean. This new bet will either offer a chance to earn kudos for the courage to trust in a retrospective analysis, or more harsh criticism for failing to give up on a failure. And the results will speak volumes about the company's future in oncology.
But there's no turning back now.
"This is a significant milestone for olaparib, and further evidence of AstraZeneca's commitment to invest in distinctive science in our core therapy areas, with a particular focus on high unmet need," said Antoine Yver, AstraZeneca's oncology R&D chief, in a statement. "We feel olaparib has real potential to significantly improve treatment decisions for this group of patients who currently have limited options, and to become the next important product in our growing oncology portfolio."
The U-turn at AstraZeneca is a plus for Salt Lake City-based Myriad Genetics, which is building out a new lab in order to provide a companion diagnostic for investigators recruiting BRCA patients for the two late-stage studies being planned.
- here's the press release
- here's the release from Myriad Genetics