Roche withdraws Gavreto approval, citing study impracticality

Roche withdraws Gavreto approval, citing study impracticality

Roche’s cancer drug Gavreto was withdrawn for the treatment of advanced RET-mutant medullary thyroid cancer, following discussions with the FDA. The drug had received accelerated approval in 2020 based on tumor shrinkage data from the ARROW trial. Roche’s Genentech unit, after evaluating the feasibility of the Phase III AcceleRET-MTC trial for full approval, determined it was no longer viable. However, Gavreto still maintains its approval for RET fusion-positive thyroid cancer, with additional data required from the ARROW and TAPISTRY trials as postmarketing requirements.

Medullary thyroid cancer represents a small portion of Gavreto’s sales, amounting to CHF 26 million last year. Roche terminated its partnership with Blueprint in February and will return Gavreto to the Massachusetts biotech, with the transition period concluding in February. Blueprint is currently seeking a new partner for Gavreto and does not anticipate the withdrawal affecting this process.

Gavreto’s other approved indication is RET fusion-positive non-small cell lung cancer, for which Roche is conducting a Phase III trial (AcceleRATE-Lung) comparing Gavreto to chemotherapy alone or in combination with Merck’s Keytruda. The drug was previously part of a larger Phase III trial, but the Gavreto arm has been closed.

Confirmatory evidence from the original ARROW trial is required by the FDA for full approval in RET fusion-positive non-small cell lung cancer. Roche’s decision to withdraw Gavreto for the treatment of RET-mutant medullary thyroid cancer may be attributed to changes in the treatment landscape and the availability of more precise RET inhibitors.

Gavreto, a drug developed by Roche, initially received approval for the treatment of RET fusion-positive non-small cell lung cancer (NSCLC). This indication also received accelerated approval, and Roche is currently conducting a Phase III trial called AcceleRET-Lung to further investigate Gavreto’s efficacy. The trial compares Gavreto against chemotherapy with or without Merck’s Keytruda in newly diagnosed RET-positive metastatic NSCLC. Gavreto was previously part of a Phase III umbrella trial that compared therapies targeting RET, ALK, and ROS with AstraZeneca’s Imfinzi in stage 3 NSCLC. However, the Gavreto arm of the trial has been closed according to a spokesperson from Genentech.

For the NSCLC indication, the FDA has requested additional data from patients in the original ARROW trial as confirmatory evidence before granting full approval, as stated by a spokesperson from Blueprint. In some cases, drugmakers have withdrawn accelerated approvals when conducting confirmatory trials becomes challenging. An example of this is Viatris’ withdrawal of the antimicrobial powder Sulfamylon due to difficulties in enrolling patients in a controlled Phase IV trial.

In the case of Gavreto’s AcceleRET-MTC trial, which aimed to study Gavreto in previously treated RET-mutant thyroid cancer, a spokesperson from Genentech mentioned that the trial was not activated due to changes in the treatment landscape over time. It is possible that the availability of RET inhibitors has led doctors to prefer more precise targeted therapies over traditional multikinase inhibitors like Gavreto. The withdrawal of Gavreto comes at a time when the FDA’s oncology department is increasing scrutiny on accelerated approvals that do not meet confirmatory trial requirements. The agency has urged the market withdrawal of certain PD-1/L1 inhibitors, PI3K inhibitors, PARP inhibitors, and other medications.

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