Roche Relief As APHINITY Trial Boosts Outlook On Its Oncology Business

Roche released positive headlines from its APHINITY trial examining use of Herceptin and Perjeta together in the adjuvant treatment of breast cancer, offering promise that its aging oncology franchise can be protected.

A huge sigh of relief accompanied Roche's announcement Mar. 2 that the keenly-awaited Phase III APHINITY trial showed that Perjeta (pertuzumab), combined with Herceptin (trastuzumab) and chemotherapy, extended disease-free survival in patients with HER2-positive early breast cancer when compared with Herceptin and chemo alone, and that no new safety signals were seen.

APHINITY's aim was to show that adding Perjeta would significantly improve invasive disease-free survival rates in women with early HER2-positive breast cancer. By meeting the primary endpoint, Roche's combo has boosted prospects the world's biggest maker of cancer drugs can off-set biosimilar threats to its oncology business with new therapies. Some 40% of group revenues are set to face biosimilar competition over the next five years.

Full APHINITY Details Likely At ASCO

But analysts and investors must await full details from APHINITY. Analysts think that will occur at this June's American Society of Clinical Oncology (ASCO) meeting in Chicago, Illinois. "Without full details of the data, some degree of hand-wringing will likely continue, in terms of just how big the clinical benefit is likely to be," Bernstein analyst Richard Wagner said in a reaction note.

"Without full details of the data, some degree of hand-wringing will likely continue, in terms of just how big the clinical benefit is likely to be."

That's because observers are closely watching Roche's succession plans for its HER2 franchise, which has already revolutionized the treatment of breast cancer. Of particular interest are new drugs Perjeta and Kadcyla (ado-trastuzumab emtansine), the antibody-drug conjugate version of Herceptin. Roche hopes therapies like those will replace revenues lost when its three top-selling drugs Herceptin, Rituxan/MabThera (rituximab) and Avastin (bevacizumab) – which account for some $20bn in yearly sales – begin to lose patent protection in the next three years.

Perjeta has already been approved in the US in combination with Herceptin in metastatic disease, and received accelerated approval in the pre-surgical, or neoadjuvant, setting, where it has been shown to reduce the size of tumors.

APHINITY is evaluating Perjeta’s ability to stop the recurrence of the disease for women who have undergone surgery, or “adjuvant” treatment, which if successful would greatly boost the number of patients eligible for the combination of HER2-blocking agents.

"These APHINITY results serve as confirmation for the conditional approval and will also assure the label-expansion approval of Perjeta for adjuvant treatment. This label expansion will help Roche increase its revenues even as it faces competition from Herceptin biosimilars," said BioMedTracker analyst David Dahan.

Encouraging Regulatory Approach

Roche said it would now discuss the APHINITY results with the FDA and European Medicines Agency (EMA) as well as HTA authorities for potential approval of the drug mixture for treating people with HER2-positive early breast cancer.

"We cannot speculate on the timing of potential regulatory decisions. We hope to bring this treatment option to patients as soon as possible," a Roche spokesperson said.

Analysts at Berenberg took heart at the regulatory approach Roche indicated it would use for the combo in the early HER2-postive breast cancer setting. "Roche intends to file on a global basis, which we think is encouraging, because this indicates it believes the data will be strong enough to secure adoption on a wide basis," they said.

The significance of the trial reflects the fact that treating breast cancer effectively and early, before it has spread, may improve the chance of preventing the disease from returning and potentially reaching an incurable stage.

Herceptin is Roche's second-biggest earner after Avastin. Some 70% of Roche’s $6.8bn Herceptin sales came last year from patients who might benefit from the combination being tested in the APHINITY trial, analysts said.

Roche had used its end-2016 results presentation in early February to play down the importance of the APHINITY trial, a ploy that only served to fan worries among investors and analysts that the study might not meet its primary endpoint. Release of its topline data should allay most of those fears.

"If the Perjeta / Herceptin combination becomes the new gold standard treatment in the adjuvant treatment of HER2-positive breast cancer it will also help protect the current Herceptin franchise from biosimilar threat. This is crucially important, as around three-quarters of Herceptin's current sales of CHF6.8bn in 2016 come from adjuvant use," analysts at Jefferies said in a reaction note.

Roche at its 2016 results presentation gave guidance for 2017 of sales growing by low- to mid-single digits at constant exchange rates – and said that presumption would not change irrespective of what the APHINITY trial's outcome was. (Also see "Cautious Roche Stresses: 'It's Not Only About APHINITY'" - Scrip, 2 Feb, 2017.)

Analysts at Berenberg in a Feb 6 commentary said they were optimistic about Roche's prospects. They noted that Roche is entering a critical period, with long-anticipated biosimilar competition likely to emerge in Europe in the second half of 2017.

Product Progress

But Roche is also launching a range of new products such as anti-PD-L1 agent Tecentriq (atezolizumab) and Venclexta (venetoclax) and has more on the way such as Roche’s not-yet-marketed Ocrevus (ocrelizumab), which is in development for relapsing-remitting MS and primary-progressive disease, and its emicuzumab (ACE910) hemophilia therapy.

"We think new product momentum will offset the headwinds over the next three to five years allowing Roche to deliver low-mid single digit sales growth for the foreseeable future. Nevertheless, there are still many moving parts that could swing top-line growth either way," they added.

Looking to the release of full APHINITY data later this year, analysts at Jefferies said that for the Perjeta and Herceptin combination to become widely used as a new standard of care, it would probably be necessary for the APHINITY trial to contain a strong clinical benefit as well as the significantly significant benefit.

That would also be important to gain payer reimbursement, given that Perjeta is currently priced at around a 50% premium over Herceptin, implying that the current monthly cost of around $4,000 for Herceptin alone would rise to some $10,000 per month for the combination, they said.

"Recent data has shown that Herceptin monotherapy can achieve a three-year invasive disease-free survival rate of around 90% and we estimate that to show a clinically meaningful improvement that will gain reimbursement, the combination will need to show a disease-free survival rate of around 92% to 94%, and a relative risk reduction of another 20% to 40%," the Jefferies analysts said.

Puma Pain

But while positive for Roche, Datamonitor Healthcare analyst Zachary McLellan says the APHINITY trial's results "are a significant blow" to Puma Biotechnology Inc. and its pan-HER inhibitor, neratinib. Puma is trying to position its lead asset for the extended adjuvant setting after treatment with Herceptin in breast cancer patients.

"Neratinib has not been studied in patients that received both Perjeta and Herceptin treatment and will not be indicated for use in these patients. So, if approved, neratinib will likely see little to no uptake in its targeted indication," McLellan told Scrip.

BioMedTracker's Dahan agreed, adding: "detailed results will be key - and it will be interesting to see how Perjeta performed in patients with hormone-receptor positive disease, a subgroup which did very well on neratinib."