Blueprint Medicines Announces FDA Approval of GAVRETO™ (pralsetinib) for the Treatment of Adults with Metastatic RET Fusion-Positive Non-Small Cell Lung Cancer
GAVRETO is a once-daily oral RET-targeted therapy developed by
"Targeted therapies have dramatically improved care for patients with non-small cell lung cancer driven by oncogenes, including EGFR and ALK, and the approval of the selective RET inhibitor pralsetinib, or GAVRETO, marks another milestone in a paradigm shift toward precision medicine," said
"GAVRETO is the second breakthrough therapy discovered by
GAVRETO was granted accelerated approval by the FDA1, and continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. In 87 patients previously treated with platinum-based chemotherapy, the overall response rate (ORR) was 57 percent (95% CI: 46%, 68%) with a 5.7 percent complete response (CR) rate, and the median duration of response (DOR) was not estimable (95% CI: 15.2 months, not estimable). In 27 treatment-naïve patients who were ineligible for platinum-based chemotherapy per the study protocol, the ORR was 70 percent (95% CI: 50%, 86%) with an 11 percent CR rate, and the median DOR was 9.0 months (95% CI: 6.3 months, not estimable). GAVRETO has warnings and precautions of interstitial lung disease/pneumonitis, hypertension, hepatotoxicity, hemorrhagic events, risk of impaired wound healing and risk of embryo-fetal toxicity.
"We applaud therapeutic advancements like GAVRETO that allow lung cancer treatment to be personalized based on the molecular drivers in a person's tumor," said
Biomarker testing for RET is the only way to identify patients with metastatic NSCLC who are candidates for treatment with GAVRETO. RET fusions can be identified with available biomarker tests, including next-generation sequencing with tumor tissue or liquid biopsies. In the ARROW trial, RET fusions were detected using next-generation sequencing, FISH or other methods.
GAVRETO is a cornerstone precision medicine for
New Drug Application Accepted by FDA for the Treatment of RET-Mutant Medullary Thyroid Cancer and RET Fusion-Positive Thyroid Cancer
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About GAVRETO (pralsetinib)
GAVRETO (pralsetinib) is a once-daily oral targeted therapy approved by the FDA for the treatment of adults with metastatic RET fusion-positive NSCLC as detected by an FDA approved test. It is designed to selectively and potently target oncogenic RET alterations. In pre-clinical studies, GAVRETO inhibited RET at lower concentrations than other pharmacologically relevant kinases, including VEGFR2, FGFR2 and JAK2. For more information, visit GAVRETO.com.
GAVRETO is not approved for the treatment of any other indication in the
Enrollment is ongoing in the Phase 1/2 ARROW trial, including for patients with various RET fusion-positive solid tumors, and the Phase 3 AcceleRET Lung trial for treatment-naïve patients with RET fusion-positive NSCLC. For more information about pralsetinib clinical trials, visit www.clinicaltrials.gov or www.blueprintclinicaltrials.com.
About RET-Altered Solid Tumors
RET activating fusions and mutations are key disease drivers in many cancer types, including NSCLC and multiple types of thyroid cancer. RET fusions are implicated in approximately 1 to 2 percent of patients with NSCLC and approximately 10 to 20 percent of patients with papillary thyroid cancer, while RET mutations are implicated in approximately 90 percent of patients with advanced MTC. In addition, oncogenic RET fusions are observed at low frequencies in colorectal, breast, pancreatic and other cancers, as well as in patients with treatment-resistant EGFR-mutant NSCLC.
Important Safety Information
Pneumonitis occurred in 10% of patients who received GAVRETO, including 2.7% with Grade 3/4, and 0.5% with fatal reactions. Monitor for pulmonary symptoms indicative of interstitial lung disease (ILD)/pneumonitis. Withhold GAVRETO and promptly investigate for ILD in any patient who presents with acute or worsening of respiratory symptoms (e.g., dyspnea, cough, and fever). Withhold, reduce dose or permanently discontinue GAVRETO based on severity of confirmed ILD.
Hypertension occurred in 29% of patients, including Grade 3 hypertension in 14% of patients. Overall, 7% had their dose interrupted and 3.2% had their dose reduced for hypertension. Treatment-emergent hypertension was most commonly managed with anti-hypertension medications. Do not initiate GAVRETO in patients with uncontrolled hypertension. Optimize blood pressure prior to initiating GAVRETO. Monitor blood pressure after 1 week, at least monthly thereafter and as clinically indicated. Initiate or adjust anti-hypertensive therapy as appropriate. Withhold, reduce dose, or permanently discontinue GAVRETO based on the severity.
Hepatotoxicity: Serious hepatic adverse reactions occurred in 2.1% of patients treated with GAVRETO. Increased AST occurred in 69% of patients, including Grade 3/4 in 5.4% and increased ALT occurred in 46% of patients, including Grade 3/4 in 6%. The median time to first onset for increased AST was 15 days (range: 5 days to 1.5 years) and increased ALT was 22 days (range: 7 days to 1.7 years). Monitor AST and ALT prior to initiating GAVRETO, every 2 weeks during the first 3 months, then monthly thereafter and as clinically indicated. Withhold, reduce dose or permanently discontinue GAVRETO based on severity.
Grade ≥ 3 hemorrhagic events occurred in 2.5% of patients treated with GAVRETO including one patient with a fatal hemorrhagic event. Permanently discontinue GAVRETO in patients with severe or life-threatening hemorrhage.
Impaired wound healing can occur in patients who receive drugs that inhibit the vascular endothelial growth factor (VEGF) signaling pathway. Therefore, GAVRETO has the potential to adversely affect wound healing. Withhold GAVRETO for at least 5 days prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of GAVRETO after resolution of wound healing complications has not been established.
Based on findings from animal studies and its mechanism of action, GAVRETO can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective non-hormonal contraception during treatment with GAVRETO and for 2 weeks after the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with GAVRETO and for 1 week after the final dose. Advise women not to breastfeed during treatment with GAVRETO and for 1 week after the final dose.
Common adverse reactions (≥25%) were fatigue, constipation, musculoskeletal pain, and hypertension. Common Grade 3-4 laboratory abnormalities (≥2%) were decreased lymphocytes, decreased neutrophils, decreased phosphate, decreased hemoglobin, decreased sodium, decreased calcium (corrected) and increased alanine aminotransferase (ALT).
Avoid coadministration with strong CYP3A inhibitors. Avoid coadministration of GAVRETO with combined P-gp and strong CYP3A inhibitors. If coadministration cannot be avoided, reduce the GAVRETO dose. Avoid coadministration of GAVRETO with strong CYP3A inducers. If coadministration cannot be avoided, increase the GAVRETO dose.
Please click here to see the full Prescribing Information for GAVRETO.
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements regarding
1 GAVRETO™ (pralsetinib) Prescribing Information (
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