Tesaro makes its case for a clean sweep with niraparib – and shares soar again

Lonnie Moulder

Lonnie Moulder

We already knew going into the big ESMO meeting that Tesaro’s PARP inhibitor niraparib had demonstrated stellar results for a range of ovarian cancer patients with BRCA mutations. But when investigators stood up to display the results of their pivotal study, a full set of data demonstrated a benefit not only for tumors that were positive for HRD, an important biomarker, but also for HRD-negative tumors.

The benefit narrows progressively by that last step, but even at a 3.1-month progression survival benefit for the HRD-negative group in the Phase III — 6.9 months versus 3.8 months — investigators laid the groundwork for advancing this drug for use without a diagnostic test developed by Myriad Genetics.

“Even in the HRD-negative community, there’s a substantial benefit,” CEO Lonnie Moulder told me in the leadup to the ESMO conference. And he’s prepared to make the case for niraparib with a full set of “randomized, controlled data we think is quite powerful.”

“Our conclusion is that all patients have a benefit and all patients must be treated,” chief investigator Mansoor Raza Mirza said at the Copenhagen meeting, according to Reuters’ report.

Their study in the New England Journal of Medicine adds that one in 5 of those HRD-negative patients demonstrated a benefit of greater than 18 months of progression-free survival, a point Tesaro will be making with regulators. The overall survival (OS) results have yet to be determined, leaving regulators to make their decisions based on PFS results.

Tesaro’s bullish position was cheered on by investors Monday morning, driving up the biotech’s shares by 21% on the added perspective. And some analysts, like Leerink’s Seamus Fernandez, helped fuel the rally with comments like this:

Avastin was approved in combination with chemotherapy in platinum-resistant ovarian cancer based on 3.4 month benefit (6.8 vs. 3.4 months for chemo alone; HR=0.38; p<0.0001). While there are several caveats to this comparison (Avastin was used in combination in a treatment setting for platinum-resistant patients and produced a lower hazard ratio with a larger n), we believe this demonstrates that the FDA can view a 3+ month improvement in mPFS as clinically meaningful.

Johnathan Lancaster, Myriad’s chief medical officer, disagreed with Tesaro’s assessment, telling Bloomberg that the HRD-negative PFS rate is not clinically significant. He backed that up by noting that AstraZeneca’s Lynparza, which managed to get approved even after a panel voted the drug down on weak early results, was not OK’d for use in BRCA negative patients with a PFS of 3.6 months.

Myriad Genetics had this to add in a statement to Endpoints News:

The NOVA study demonstrated the efficacy of both the drug and Biomarker. Despite the super sensitive platinum responders selected for the study, myChoice HRD was able to stratify based on benefit. The FDA will need to decide whether the 3.1 month benefit in HRD negative patients is sufficient. This is particularly important in the context of drugs that have toxicity in the maintenance setting where the alternative is no therapy at all.

For patients with non-germline BRCA mutations that were HRD positive, the PFS benefit was much more distinct, a median 12.9 months versus 3.8 months. The drug was tested as a maintenance therapy in platinum-sensitive, recurrent ovarian cancer. You can see the full set of data and the discussion in the New England Journal of Medicine.

Regardless of the outcome of the debate over HRD status, Tesaro is lining up for a near term approval that should leave them in a strong market position relative to Lynparza or Clovis Oncology, which saw its stock price take a hit yesterday over data drawn from a different set of ovarian cancer patients. The company has been insisting that you can’t compare studies, but it’s done every day. And as Clovis’s stock dropped 18% over the course of Friday, it wasn’t faring very well.

Pfizer, meanwhile, plans to advance their rival PARP drug talazoparib, newly acquired in its $14 billion Medivation acquisition.

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Sr. Manager, Regulatory Affairs, CMC
CytomX Therapeutics San Francisco, CA
Marketing Associate - Demand Generation
Catalytic Data Science Charleston, SC
Associate Principal, Life Sciences Partnerships
Flatiron Health New York City or San Francisco

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