The FDA’s approval of Genentech Inc.’s Gavreto (pralsetinib) for treating adults with metastatic rearranged during transfection (RET) fusion-positive non-small-cell lung cancer (NSCLC) follows the FDA’s May approval of Eli Lilly and Co.’s Retevmo for patients whose tumors have a RET alteration.

Jeffrey W. Albers, Blueprint’s CEO, president and director, was asked on the Sept. 8 call if physicians treating patients with Retevmo might see any benefit by switching to Gavreto. Albers said that “these are really sick patients and having options is a good thing. And I have said it 100 times that for whatever reason, a patient doesn't tolerate one of our medicines, I hope there's another therapy that they can get. And so I think at the physician level, you're going to see some of that, that patients see both therapies in short order maybe over a longer period of time. I think we need to generate more data to really understand that in greater detail.”

Piper Sandler analysts wrote Sept. 8 that updated efficacy data continue to favor competitor Retevmo, and a pulmonary safety warning for interstitial lung disease (ILD)/pneumonitis, which can drive lung fibrosis, “doesn’t seem to bode well for Gavreto in NSCLC. … We do believe the recent Roche deal for Gavreto will help drive faster commercialization and more efficient patient identification, but despite this, we think the competitive edge for RET inhibitors continues to lie with LLY’s Retevmo, with its better efficacy and safety profile.”

Gavreto will be commercialized in the U.S. by Genentech, part of the Roche Group, along with Blueprint Medicines Corp., which developed the once-daily oral therapy. Outside the U.S., Roche will handle commercialization.

SVB Leerink analyst Andrew Berens wrote Sept. 8 that the approval will mean Blueprint will likely shift its attention to its other emerging pipeline programs, such as Ayvakit (avapritinib) for systemic mastocytosis and BLU-945 for triple mutant EGFR. Berens also wrote that RET dynamics will not be a key driver of Blueprint shares going forward, either long or short term.

“We believe Roche's commercial infrastructure will be competitive with Lilly's Retevmo, which reported initial revenue of [about] $6.3 [million] in 2Q20, following the accelerated approval in May 2020,” Berens wrote. “We expect the RET diagnosis rate to rapidly increase with the [two] companies promising drugs in this arena.”

Gavreto will be priced consistently on a per-milligram basis at approximately $19,250 for a 30-day supply of the 400-mg dose, Christina Rossi, Blueprint’s chief commercial officer, said on the conference call with investors. She said the therapy will be available to patients within the coming week.

When approved in May, Lilly said Retevmo's list price would be about $20,600 per 30 days of therapy, which the company said is generally in line with other oral targeted therapies.

Gavreto’s indication was approved Sept. 4 under the FDA’s accelerated approval program and a few months before its Nov. 23 PDUFA date. Along with the approval, the FDA also granted priority review to Gavreto for treating advanced or metastatic RET-mutant medullary thyroid cancer and RET fusion-positive thyroid cancer.

Blueprint stock (NASDAQ;BPMC) sagged 3.9% on Sept. 8 to close at $70.19. The stock started the year at $82.19 per share. Lilly stock (NYSE:LLY) bobbed all day, closing 1.06% down at $149.31 as shares dropped as low at $148.71 and as high as $151.21.

The Gavreto approval was based on results from the phase I/II arrow study evaluating the safety, tolerability and efficacy of Gavreto, administered orally in patients with RET fusion-positive NSCLC, RET-mutant medullary thyroid cancer (MTC), RET fusion-positive thyroid cancer and other RET-altered solid tumors. The data showed Gavreto produced durable clinical responses in patients with RET fusion-positive NSCLC with or without prior therapy, and regardless of RET fusion partner or CNS involvement. Gavreto demonstrated an overall response rate of 57% (95% CI: 46%, 68%) and complete response rate of 5.7% in the 87 people with NSCLC previously treated with platinum-based chemotherapy, and the median duration of response was not reached (95% CI: 15.2 months, not reached).

Lilly’s Retevmo was designed to inhibit native RET signaling as well as anticipated acquired resistance mechanisms. Its approval was founded on data from the Loxo Oncology Inc.-initiated phase I/II LIBRETTO-001 study, the largest clinical trial ever conducted in RET-altered lung and thyroid cancers, according to Lilly.

RET is one of seven NSCLC biomarkers that can be targeted with an FDA-approved therapy. This is Genentech’s sixth FDA-approved therapy for treating lung cancer.

It is the second FDA approval of the year for Blueprint. On Jan. 10, the FDA approved Ayvakit, an inhibitor of KIT and platelet-derived growth factor receptor alpha, for treating adults with unresectable or metastatic gastrointestinal stromal tumor harboring a PDGFRA exon 18 mutation, including PDGFRA D842V mutations. The approval came one month ahead of its Feb. 14 PDUFA date.