Puma doubles on FDA panel’s nod for breast-cancer drug; but Swiss giant’s challenger lurks

The News:

Puma Biotechnology Inc.’s (Los Angeles) experimental breast cancer drug reduces the risk of disease recurrence and should be approved, an advisory committee to the US Food and Drug Administration concluded on Wednesday (May 24, 2017) (pdf).

@US_FDA advisory committee approves Puma Biotechnology Inc. #breastcancer drug Click To Tweet

The panel voted 12 to 4 in favor of the drug, neratinib, saying its benefits outweighed the risks, though panelists noted that the magnitude of the benefit was modest. The FDA is not obliged to follow the recommendations of its advisory panels, but typically does so, Reuters reminds us.

The difference in the rate of disease-free survival between patients taking neratinib and those taking a placebo after two years was 2.3%, meaning that out of 100 women, cancer returned in 5.8 women in the neratinib group compared with 8.1 in the placebo group.

“The benefit in absolute terms is relatively modest,” said Dr. Grzegorz Nowakowski, associate professor of medicine and oncology at the Mayo Clinic in Rochester, adding: “toxicity appears to be manageable.”

The most significant side effect of the drug was diarrhea, which affected 95% of patients. In 40% of cases, the diarrhea was severe. In total, 28% of patients discontinued neratinib due to a side effect.

The drug is designed to treat early stage breast cancer in patients with the HER2 genetic mutation whose tumor has been surgically removed and who have been treated with Roche Holding AG’s Herceptin, a drug which itself reduces the risk of the disease returning.

Panelists who voted against approval were not convinced the drug would be effective in the overall population for which it would be approved, though some thought it could potentially be beneficial in a subset of patients.

Puma’s shares closed at $74.00 Wednesday, up 96% so far this week.

Steve’s Take:

Is it time to snatch up Puma shares? Or first wait for the inevitable correction. A positive vote–and an approval–are still no sure thing. The FDA brought up several issues in the documents that could be deal-killers.

And there’s the less-discussed matter of a competing drug from Roche Holding AG that, if approved, could spell the end of days for the California group.

Then again, shares are down a whopping 73% from their Sept. 2014 summit. That’s a lot of potential upside if that peak had even a scrap of validity to it back then.

Let’s remember that Puma’s not applying to sell neratinib in patients who have no other hope. Instead, it’s asking to sell the drug for use in women who have already had their cancer surgically removed, and who have also been treated with Herceptin, a Roche breast cancer drug, to keep it from coming back. Then they would take neratinib (tentative brand name: Nerlynx) to further lower their risk of breast cancer returning.

In a big clinical trial, neratinib reduced the rate of breast cancer recurrence within two years by a third. Cancer returned in 8.1% of women who didn’t take neratinib, versus 5.8% who did.

Out of 100 women treated for two years, two would not get cancer. That’s a real but small benefit, Forbes points out–although it might be bigger in a subset of women whose tumors test as hormone-receptor positive. But neratinib came with a downside: diarrhea in 95% of patients. For 40% of patients, the diarrhea was serious. It appears treatment with loperamide, the active treatment in Imodium, can reduce the diarrhea somewhat.

Other drugs have been approved for use after a cancer appears to be gone (called “adjuvant use” by doctors), and more are definitely coming. What Puma must be sweating though is the expert panel’s decision for Roche’s breast cancer drug Perjeta, which will likely happen before the FDA is expected to make a final decision on neratinib.

So where does neratinib fit in, and will doctors and patients want this drug?

“There’s no ex­cla­ma­tion point after my ‘yes’,” said An­drew Sei­d­man, an on­col­o­gist at Memo­r­ial Sloan Ket­ter­ing. “It’s just a yes.”

He added that he was happy that the drug looks durable and for the sta­tis­ti­cal analy­ses ap­plied to the data, given the sig­nif­i­cant changes to the study de­sign.

“I do think that physi­cians will se­lect pa­tients very se­lec­tively for using this,” he noted according to EndPoints, echo­ing a con­cern that the ap­proval the com­pany was seek­ing was too broad given the data avail­able.

The bears’ ar­gu­ment that the drug trig­gered such se­ri­ous ad­verse events that it would be rejected by the FDA ran into the ex­perts’ sup­port for the mar­ginal ben­e­fit the drug demon­strated, im­prov­ing dis­ease-free sur­vival in HER2 pos­i­tive pa­tients by 2.3%. About 94.2% of pa­tients in the ner­a­tinib arm were alive with­out their dis­ease pro­gress­ing at two years, com­pared with 91.9% in the con­trol arm.

One of the biggest is­sues high­lighted in the FDA’s writ­ten re­view of the drug was that agency of­fi­cials had ad­vised Puma not to file based on the data from their piv­otal trial. That didn’t seem to weigh heav­ily on the panel, though Puma won’t know for sure if it’s out of the woods until the FDA pro­vides a for­mal de­ci­sion.

Panel votes are not bind­ing on the full FDA.

Bottom Line:

Roche’s successful Aphinity trial of Perjeta, reported in March, will affect not only the fortunes of the Swiss company’s breast cancer franchise but also could determine whether upstart Puma has much of any future whatsoever.

Expectations had been high for Aphinity, testing Perjeta in combination with Herceptin and chemotherapy in post-surgical patients, and a substantial part of Perjeta’s $5 billion peak sales forecast were attributed to its success.

On the other hand, Puma’s neratinib, which is seeking regulatory approval in a broadly similar setting, could be rendered irrelevant by Aphinity because of Perjeta’s shorter treatment duration and lower toxicity.

With the “Aphinity” study success in March, Perjeta/Herceptin is likely to become the new standard of care for adjuvant breast cancer therapy, according to The Street. That squeezes out neratinib, in part because there are no data to support the use of neratinib after Perjeta/Herceptin. Neratinib’s approval chances had been weighed down by clinical data demonstrating a small benefit for breast cancer patients and extremely high rates of serious diarrhea.

The global treatment market for non-hematological cancers, which includes breast, colorectal, lung and prostate cancers, among others, will almost double from $72.9 billion in 2014 to $140.8 billion in 2021, at a compound annual growth rate (CAGR) of 9.9%, according to business intelligence provider GBI Research.

Yes, this is one colossal market with a lot of companies chomping at the bit to take big chunk out of it.

Steve's Take: Puma's #neratinib may not be able to beat @Roche's #Perjeta / #Herceptin combo Click To Tweet

Assuming that both Puma’s neratinib and Roche’s Perjeta/Herceptin are ultimately approved, it’s hard to see doctors and patients choosing the newer entry. But strange things can and do happen when the FDA weighs in with its final decision for any drug. Perhaps a pot of gold still awaits the upstart and its faithful investors.

Steve Walker has no position in any stocks mentioned. MedContent Inc. has no position in any stocks mentioned. MondayMorning.com has a disclosure policy.