All stocks have a bear thesis. That includes Tesaro(TSRO) - Get Report , which is up big Monday because of clinical trial results presented over the weekend showing its PARP inhibitor delayed the recurrence of tumors in ovarian cancer patients.
Tesaro is the top-performing biotech stock Monday, with shares up 23% to $121.80. Analysts left and right are reiterating buy ratings and raising price targets.
The Tesaro PARP inhibitor is called niraparib and it looks really promising as a maintenance therapy for ovarian cancer patients. I wrote about the phase III data on Saturday.
Positive data does not eliminate all risks. For Tesaro, the lingering controversy centers around the size of the ovarian cancer patient pool it can reach with niraparib, assuming the drug is approved for maintenance therapy. (The company will submit the drug to regulators before the end of the year.)
Tesaro is shooting for the broadest possible approval. It will ask regulators in the U.S. and Europe to approve niraparib to treat all patients with recurrent platinum-sensitive ovarian cancer. That's about 20,000 patients each year.
The company's enterprise value is approaching $5 billion, which means investors are also assuming a broad niraparib label.
The risk -- and the gist of the Tesaro bear thesis -- is that the stock is overvalued if regulators decide to grant marketing clearance for niraparib only in a smaller, more restricted population of ovarian cancer patients.
Approximately one-third of the 20,000 patients targeted by Tesaro could be excluded, if regulators in the U.S. and Europe take a more cautious approach to niraparib's label.
That number jumps to two-thirds of the 20,000 patients if the regulators get really risk averse.
Differences in the genetic makeup of ovarian cancer -- and how these mutations impact the response to niraparib -- explains why the potential size of Tesaro's commercial opportunity remains controversial.
I'll get to parsing Tesaro's niraparib data based on genetic signatures of the tumors in a moment. But first, some quick perspective on what it might take to get a PARP inhibitor approved in the ovarian cancer maintenance setting.
The U.S. Food and Drug Administration has never approved a PARP inhibitor for ovarian cancer maintenance therapy. AstraZeneca(AZN) - Get Report tried in 2014 with its PARP inhibitor Lynparza, but was denied. (The FDA did approve Lynparza to treat a different group of ovarian cancer patients.)
In rejecting AstraZeneca's submission for maintenance therapy, FDA reviewers suggested that delaying the re-growth of ovarian cancer tumors by a minimum of six months was "clinically meaningful."
The FDA's thinking on approval standards for ovarian cancer maintenance therapy may have shifted since 2014, but for now, a six-month delay in tumor progression seems like the precedent.
In Tesaro's phase III study, ovarian cancer patients born with a mutation to a tumor suppressor gene known as BRCA were helped the most by niraparib. In these "germline BRCA mutant" patients, niraparib delayed tumor progression by a median of greater than 15 months compared to placebo.
Niraparib's approval in these ovarian cancer patients -- representing one-third of the total -- seems guaranteed.
The remaining two-thirds of ovarian cancer patients enrolled in Tesaro's clinical trial were not born with the BRCA gene mutation. In these "non-germline BRCA mutation" patients, niraparib delayed tumor progression by a median of 5.4 months.
The niraparib benefit in these patients was statistically significant but perhaps not clinically meaningful based on the FDA's prior suggestion. The Tesaro result falls just a tiny bit short of that six-month threshold.
Tesaro used another genetic test to further parse the ovarian cancer patients with non-germline BRCA mutations. The company looked at a tumor mutation in another gene called HRD.
In non-germline BRCA patients who had HRD-positive tumors, niraparib delayed tumor progression by a median of 9.1 months compared to placebo. Statistically significant. That's well within the FDA's guidance on what constitutes a clinically meaningful treatment effect for maintenance therapy in ovarian cancer.
That leaves one last group of ovarian cancer patients -- those with the non-germline BRCA mutation and tumors that are HRD negative. These patients benefited the least from treatment with niraparib. At the median, tumor progression was delayed by only 3.1 months -- also statistically significant but half the FDA's suggested threshold for a meaningful benefit.
There were 188 ovarian cancer patients out of 553 total enrolled in Tesaro's phase III study who fell into this non-germline BRCA/HRD negative bucket. That's represents 34% of the total patients.
Tesaro believes it can convince FDA and European regulators that even this last group of ovarian cancer patients benefit from maintenance therapy with niraparib, so they should be included in the drug's label.
If Tesaro fails, niraparib's commercial opportunity as an ovarian cancer maintenance therapy could be cut by one third, or as much as two thirds. That's a lot of patients and drug sales at risk, depending on how the FDA decides.
That's the Tesaro bear thesis which emerged from this weekend's niraparib data results.
Adam Feuerstein writes regularly for TheStreet. In keeping with company editorial policy, he doesn't own or short individual stocks, although he owns stock in TheStreet. He also doesn't invest in hedge funds or other private investment partnerships. Feuerstein appreciates your feedback; click here to send him an email.