Rigel Warns Physicians About Fatal Infections from Gavreto

Rigel Pharmaceuticals is warning physicians about a safety concern regarding Gavreto (pralsetinib). An analysis of the ongoing phase 3 AcceleRET-Lung trial in patients with non-small cell lung cancer (NSCLC) has found that there is a risk of severe and fatal infection, including severe opportunistic infections, in patients treated with Gavreto.

The analysis found that fatal adverse events were reported in 14 patients (13.0%) in the pralsetinib arm versus five patients (4.8%) in the standard of care arm. Of these fatal events, fatal infection events occurred in five patients (4.6%) in the pralsetinib arm, and none in the standard of care arm.

At the time of the review, 108 patients had received treatment with pralsetinib, and 104 patients had received treatment in the standard of care arm. Severe (grade 3-5) infection events occurred in 28 (25.9%) pralsetinib treated patients versus 8 (7.7%) patients receiving standard of care. The risk ratio was 3.33 (a ratio of more than 1 indicates potential for harm.)

Half of the severe infections in pralsetinib treated patients occurred within the first 66 days of treatment. About half of the severe infections were lung infections. Severe opportunistic infections, including pneumocystis jirovecii pneumonia, cytomegalovirus pneumonia, legionella pneumonia and esophageal candidiasis occurred in 7 (6.5%) of pralsetinib treated patients, and no patients in the standard of care arm.

In the warning letter, Rigel officials indicated these findings support including the risk of severe infection in the Warnings and Precautions section of the label.

Developed by Blueprint Medicines and Roche, Gavreto is a only once daily, oral RET-inhibitor therapy. Gavreto is indicated to treat adult patients with metastatic rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC), as well as adult and pediatric patients 12 years of age and older with advanced or metastatic RET fusion-positive thyroid cancer through an accelerated approval.

Roche had terminated its development agreement with Blueprint in February 2023. Rigel announced in June 2024 that it had acquired the U.S. rights to Gavreto from Blueprint Medicines. In 2023, Gavreto generated about $28 million in U.S. sales.