Roche, Blueprint take on Lilly with FDA approval for RET cancer drug Gavreto

Stamp with blue ink that says "FDA Approved"
Blueprint Medicines and partner Roche have won FDA approval for RET inhibitor Gavreto to challenge Eli Lilly's first-to-market Retevmo. (Olivier Le Moal/Getty Images)

It was only May when Eli Lilly’s Retevmo became the first FDA-approved drug for RET-altered tumors. Now, a rival therapy has arrived with the marketing clout of a Big Pharma cancer specialist.

Blueprint Medicines and recently signed-on partner Roche have snagged an FDA green light for Gavreto (pralsetinib) in non-small cell lung cancer that bears an abnormality in the RET gene.

The drug will become “the primary focus and priority” for the company’s marketing team, which employs more than 40 sales reps, Blueprint’s chief commercial officer, Christy Rossi, said ahead of the approval. Another part of the Blueprint commercial group is focused on patient identification, as testing is important for a targeted therapy such as Gavreto, she added.

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Those aspects make Roche, a cancer therapy and diagnostic giant, the ideal partner for Blueprint. Roche brings expertise in precision cancer drugs that it can use in its dealing with healthcare providers, and it can help identify eligible patients by driving testing. Blueprint, for its part, brings to the table its knowledge around Gavreto specifically, Rossi said.

And Roche clearly likes what it’s seen so far, having shelled out $775 million upfront for Gavreto rights, including a $100 million in equity investment in Blueprint.

RELATED: Roche to pay Blueprint $775M for pralsetinib rights, setting up showdown with Lilly

The FDA cleared Gavreto based on Blueprint's phase 1/2 Arrow study, in which the RET inhibitor significantly shrank tumors in 61% of NSCLC patients who had previously received chemotherapy and provoked a response in 73% of untreated patients, according to data presented at this year’s American Society for Clinical Oncology (ASCO) virtual event. In the drug's approved label, the updated response rates decreased to 57% and 70%, respectively.

Regulators based their May approval for Lilly's Retevmo, meanwhile, on results from the Libretto-001 trial, which showed a 64% response rate in patients with prior platinum treatment and an 85% response rate for those in the newly diagnosed group.

Comparing across different trials can be problematic, though, and Rossi, attributed that difference in the treatment-naïve numbers to different patient populations within the trials. Many patients in the Arrow study, for example, had central nervous system metastasis, which usually spells poor treatment outcomes.

But on the flip side, Gavreto does have some advantages over its Lilly rival. The Blueprint-Roche drug eradicated signs of tumor in 5% of previously treated patients and in 12% in new cases. By contrast, Retevmo triggered a lower 1.9% complete response rate in platinum-treated patients and a 0% rate in the untreated group.

RELATED: Lilly cashes in on Loxo buyout with FDA approval for first-in-class cancer drug Retevmo

These complete responders could see longer-lasting responses, which in turn could mean longer treatment with Gavreto, Rossi indicated. “You really want to keep patients in response for a long period of time, and that’s what cancer patients really want,” she said.

What’s more, Gavreto boasts some safety advantages, Rossi noted. While both Retevmo’s and Gavreto’s labels bear warnings against hypertension, liver toxicity and hemorrhages, Retevmo has a QT interval problem on its label.

In a May note to clients, SVB Leerink analyst Andrew Berens said Gavreto’s tolerability advantage “could be commercially relevant, especially in the community setting or when the drug moves into earlier lines of therapy like the adjuvant setting, where the duration of treatment is longer and the safety/tolerability bar is higher,” though he acknowledged there wasn’t a clear efficacy winner between the two drugs.

But fast forward to today, Gavreto bears an additional warning for interstitial lung disease/pneumonitis. Overall, about 15% of NSCLC patients were forced to permanently stop Gavreto because of side effects, up from 4% in the previous update and well above the 5% Retevmo put up in its clinical trial.

Gavreto is given once daily, while Retevmo comes as a twice-daily regimen. “Once you get above once-daily dosing, it becomes difficult for patients to remember to take their therapy at the right time every day,” Rossi said, touting Gavreto’s administration schedule as a differentiator.

RELATED: Blueprint's Ayvakit gets FDA no-go in new stomach cancer use but presses ahead in blood disorder

For Blueprint, the Gavreto OK comes less than a year after the Massachusetts biotech’s less-than-ideal first commercial launch.

Its Ayvakit landed a narrowed go-ahead in January to treat patients with rare gastrointestinal stromal tumors (GIST) carrying PDGFRa exon18 mutations, but Blueprint decided not to pursue any other GIST indications after a phase 3 failure—and, hence, an FDA rejection—in a broader, late-line GIST population.

Beyond NSCLC, an application or Gavreto in RET-mutant medullary thyroid cancer and RET fusion-positive thyroid cancer is under the FDA's real-time oncology review. The drug is also being explored in tumor agnostic indications.

“We remain committed to finding personalized treatment options for people with cancer based on specific genomic or molecular alterations,” said Levi Garraway, chief medical officer and head of global product development at Roche's Genentech. “And we look forward to partnering with Blueprint Medicines to further explore the potential of Gavreto across multiple RET-altered tumor types.”

Editor's Note: The story has been updated with additional information about Gavreto's safety and a statement from Genentech CMO Levi Garraway.

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