Puma Biotech's Nerlynx remains a dud. Will a breast cancer expansion turn things around?

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Puma Biotech's breast cancer med Nerlynx is already struggling in the extended adjuvant setting, and long-term concerns mount as competitive rivals from Daiichi Sankyo and AstraZeneca and Seattle Genetics enter its targeted new field. (nito100/iStock/Getty Images Plus)

Sales of Puma Biotech’s only commercial product—breast cancer drug Nerlynx—still need improvement, company chief Alan Auerbach acknowledged. But as one analyst sees it, a label expansion may not even be enough to save the struggling med amid increased competition.

Nerlynx sold $58.7 million in the fourth quarter—growing from the $53.5 million it posted in the third quarter—in part aided by a 9.9% list price increase in September, SVB Leerink analyst Thomas Smith noted in a Friday memo to clients.

On a conference call Thursday, Puma management pointed to the potential of an expansion into third-line HER2-positive metastatic breast cancer. But Smith said his team remains “cautious on the commercial prospects for Nerlynx in this setting.”

The good news is Nerlynx sales came in 6% above industry watchers’ expectations in Q4. Total prescribers increased by about 6.7% sequentially, as the number of bottles sold rose 5%, though Auerbach attributed that rise mainly to “inventory increase.”

New-to-brand scripts in the quarter actually dropped 16.5% from Q3, mainly around the holidays in November and December, the chief executive explained. However, shipped bottles also dropped 10% year over year. Smith argued the decline points to continued pressure for the drug in its currently approved indication, extended adjuvant; Nerlyx is given after Roche’s Herceptin post-surgery to help prevent cancer recurrence.

“We believe pressure in this setting is likely to persist, given the uptake of novel, more effective agents in the adjuvant setting (Perjeta, Kadcyla) lessening the need for extended adjuvant therapy,” Smith said, referencing a pair of Roche meds.

A major obstacle that’s been hurting Nerlynx uptake is patient discontinuation because of diarrhea, a side effect of the drug. In October, the FDA approved a label addition for Nerlynx that says antidiarrheal prophylaxis or dose titration can help reduce serious diarrhea events.

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Puma recently did some market research and found an increase in the percentage of patients continuing to take the drug after six months for those who started it at a lower dose versus those who started at the standard strength, according to Auerbach. “This data is early but encouraging, and we will continue to monitor this trend in the future,” he said during the call.

After the Q4 new-to-brand slowdown, the company did see a 30% jump in the number of new patients signing up through its specialty pharmacy channel in January. However, because it usually takes two weeks for a patient to actually get the drug, and as more patients are starting with a lower dose, 2020’s first quarter might still be weak, Auerbach warned.

One key near-term event Puma’s counting on is a potential FDA nod for Nerlynx in tandem with Roche’s Xeloda to treat breast cancer patients who have already failed two lines of therapy. The FDA has set a decision date for April.

The application is based on the phase 3 Nala trial. According to data presented at last year’s American Society of Clinical Oncology annual meeting, the Nerlynx-Xeloda combo cut the risk of disease progression or death by 24% compared with Novartis’ Tykerb plus Xeloda.

Smith labeled the benefit over Tykerb as “modest.” But perhaps more concerning for Puma is mounting competition, he figures. Daiichi Sankyo’s AstraZeneca-partnered antibody-drug conjugate Enhertu recently entered the exact same setting bearing blockbuster hopes. And those are based on data showing an impressive estimated one-year survival rate of 86% for a group of patients who had had a median six prior therapies.

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Then there’s also Seattle Genetics’ TKI tucatinib, which just nabbed an FDA priority review for its application in patients who have received at least three prior HER2-directed agents in any setting, including neoadjuvant, adjuvant or ordinary treatment. Clinical data showed that adding tucatinib to Herceptin and Xeloda reduced the risk of disease progression or death by 46% over the backbone regimen alone. Even among patients with brain metastases, the tucatinib cocktail delivered a 52% benefit.

In September, the FDA granted Nerlynx its orphan drug designation for the treatment of breast cancer patients with brain metastases. As tucatinib has shown strong data in this subgroup, “we believe Nerlynx revenue from off-label use in patients with brain metastases may be pressured,” SVB Leerink’s Smith wrote in the note.

For 2020, Puma anticipates that Nerlynx sales will check in between $215 million and $225 million, slightly up from the $211.6 million the drug generated in 2019. The forecast doesn’t include any contribution from the potential expansion into the third-line metastatic indication.