Tesaro won its niraparib approval not just early, but with no diagnostic hurdles for patients to clear. So, what’s next for AstraZeneca and Clovis Oncology and their rival meds, which are approved only to treat patients with a BRCA genetic mutation?
For AstraZeneca, it’s priority review for Lynparza, in the very setting where niraparib—now known as Zejula—will launch next month.
That would be maintenance therapy, for women with recurrent ovarian cancer who respond to platinum-based chemo. Lynparza’s now on track for a speedy review for those patients, with a decision date in the third quarter, AstraZeneca said Tuesday. Right now, the drug is only approved for patients who’ve failed on three previous rounds of chemotherapy.
Approval in that setting would make Lynparza available to a much larger set of patients. But AstraZeneca may be eyeing a bigger expansion.
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According to the company’s Tuesday statement, the application now under review is based on a phase III study in patients with the BRCA gene mutation. In that Solo-2 study, Lynparza staved off cancer progression for a median 30 months under one blinded analysis, compared with 5.5 months in the placebo arm. The official endpoint came in at 19.9 months, compared with 5.5 months, a 14.4 month survival advantage.
But as Jefferies analyst Eun Yang pointed out in a Tuesday note, Lynparza also has under its belt a phase 2 study that included patients without the BRCA mutation. “While it remains to be seen, AstraZeneca’s Lynparza has potential for a broad label based on Study 19 (in addition to Ph3 Solo-2), similar to Tesaro’s Zejula,” Yang wrote.
AstraZeneca believes Lynparza could win an approval in all patients, regardless of their BRCA status, Mika Sovak, executive director and Lynparza global development lead, told the Pink Sheet earlier this month—if the company can persuade the FDA to take a “totality of the evidence” approach.
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Asked about that possibility, an AstraZeneca spokeswoman said the company’s discussions with regulatory authorities are confidential.
What evidence would fall under that “totality” is a key question. As the Pink Sheet points out, the FDA has expressed reservations about that phase 2 study before, and at least one analyst has said that the data there wouldn’t be enough to support a broader approval.
Meanwhile, AstraZeneca announced a move Tuesday that could prime the maintenance market and potentially put non-BRCA patients in line for the therapy in that setting. The company launched an expanded access program that would offer patients maintenance therapy with Lynparza tablets—a formulation that would win its first approval with this new indication.
“This program is available to eligible patients with platinum-sensitive relapsed high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer as a maintenance treatment, following complete or partial response to platinum-based chemotherapy,” the company said via email. The ClinicalTrials.gov listing for the program doesn’t mention BRCA mutation status as a criterion for inclusion or exclusion.
Meanwhile, AstraZeneca is piling up data for Lynparza in other types of cancer including breast cancer. Last month, the pharma giant rolled out phase 3 results showing that Lynparza could top standard-of-care chemo at holding off cancer progression in patients with HER2-negative breast cancer and BRCA1 or BRCA2 mutations.
And as AZ chief medical officer Sean Bohen pointed out at the time, they’re the first positive phase 3 data for any PARP med outside the ovarian cancer arena. “This is highly encouraging for the development of our broad portfolio which aims to treat multiple cancers by targeting DNA damage response pathways,” he said in a statement.