AstraZeneca’s (AZ) hopes of getting early approval of its cancer drug olaparib were dashed yesterday after an FDA advisory committee said more safety and efficacy data was needed.
The panel of external exports voted by 11 to 2 against accelerated approval for AZ’s olaparib as a maintenance treatment for women with relapsed ovarian cancer, saying it still has questions about the drug’s safety as well as the efficacy data, which show a benefit on progression-free survival.
Olaparib is in pole position among the much-anticipated PARP inhibitor class of anticancer agents and is being developed for use in women with ovarian cancer who have a specific mutation (gBRCA) and have responded to platinum-based chemotherapy.
AZ was trying to secure approval based on the results of a pivotal phase II trial (Study 19) in 265 patients which showed that the average PFS in women treated with olaparib was 8.4 months, compared to 4.8 months for placebo.
“This was a small dataset with no improvement in overall survival and no improvement in quality of life,” said panellist James Liebmann of UMass Memorial Medical Centre during the meeting. “The benefits demonstrated need to be borne out in a larger randomized trial.”
That means AZ will now have to wait for data from the ongoing SOLO2 trial, due to complete at the end of 2015, unless the FDA chooses not to follow its advisory committee’s advice.
Not standing on AZ’s favour in the advisory committee meeting is that the results of Study 19 initially prompted AZ to announce it was dropping the drug in 2011 before restarting development after a re-analysis of the data and a formulation improvement to reduce the number of pills taken per day.
Moreover, the late-stage failure last year of another PARP inhibitor – Sanofi’s iniparib – because of a lack of efficacy may have encouraged caution on the behalf of the panellists.
At the moment there are no approved drugs to treat this cancer population, according to the FDA, which notes relapsed ovarian cancer is invariably a fatal disease with a five-year survival rate of 27 per cent.
“We are disappointed with today’s recommendation,” said AZ’s chief medical officer Briggs Morrison. “We strongly believe that olaparib has the potential to provide patients with relapsed BRCA-mutated ovarian cancer and their doctors with a much-needed treatment option.”
During its defence against Pfizer’s aborted takeover attempt last month, AZ predicted sales of olaparib should reach sales of around $2bn, presumably predicated on approval by the FDA’s October review deadline.
That makes it a key pipeline asset in the company’s bid to swell sales to more than $45bn in 2023, which is the centrepiece of chief executive Pascal Soriot’s strategic plan for the company in the coming years.
AZ is also planning additional studies of olaparib in cancers linked to BRCA mutations, including breast cancer, and will look at the drug in combination with other therapies in prostate and gastric cancers.
While olaparib could still reach the market based on the SOLO2 data, any negative newsflow might encourage shareholders to become more favourable to a renewed Pfizer bid when the moratorium period under UK takeover law comes to an end later this year.