Originally published by our sister publication Pharmacy Practice News
Rigel Pharmaceuticals announced that it has entered into a definitive agreement to acquire the U.S. rights to pralsetinib (Gavreto) from Blueprint Medicines Corp. Pralsetinib is a once-daily, small-molecule, oral kinase inhibitor of wild-type rearranged during transfection (RET) and oncogenic RET fusions. Pralsetinib is approved by the FDA for the treatment of adult patients with metastatic RET fusion–positive non-small cell lung cancer (NSCLC) as detected by an FDA-approved test.
“NSCLC is the most common type of lung cancer in the U.S. with RET fusions representing 1-2% of the patient population. Gavreto is a targeted treatment option with an established safety profile that has shown durable responses in RET fusion-positive NSCLC patients and represents a compelling addition to our commercial portfolio,” said Raul Rodriguez, Rigel’s president and CEO.
“Gavreto is one of only two approved RET inhibitors on the market for patients. We are confident in our ability to effectively transition Gavreto to our distribution network and utilize our robust capabilities to enable both existing and new patients to continue to have access to this important treatment option,” said Dave Santos, Rigel’s chief commercial officer. “The addition of Gavreto will be highly synergistic with our current product portfolio, leveraging our existing commercial infrastructure and enabling us to expand into solid tumors.”
Gavreto is also approved for the treatment of adult and pediatric patients 12 years of age and older with advanced or metastatic RET fusion–positive thyroid cancer who require systemic therapy and who are radioactive iodine–refractory, if radioactive iodine is appropriate. This indication was approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
Discussions with the FDA regarding confirmatory requirements are ongoing.
Rigel expects to complete the transition of the asset and start recognizing product sales in the third quarter of 2024. Rigel will provide additional details on this transaction at its upcoming quarterly earnings call in early March.
Rigel’s acquisition of the U.S. rights to pralsetinib is concurrent to a previously announced Roche decision to terminate the pralsetinib collaboration agreement with Blueprint effective Feb. 22, 2024. According to a statement from the company, Genentech, a member of the Roche Group, is committed to patients and working with Rigel and Blueprint to ensure current and newly prescribed patients can access pralsetinib without interruption through the transition period, with specific next steps and timing to be communicated to key stakeholders, including healthcare providers, in the next few weeks.
About NSCLC
It is estimated that over 230,000 adults in the United States will be diagnosed with lung cancer in 2024. Lung cancer is the leading cause of cancer death in the United States, with NSCLC being the most common type accounting for 80% to 85% of all lung cancer diagnoses. RET fusions are implicated in approximately 1% to 2% of patients with NSCLC (Clin Cancer Res 2017;23[8]:1988-1997).
About Pralsetinib
Indications
Pralsetinib is indicated for the treatment of:
• adult patients with metastatic RET fusion–positive NSCLC as detected by an FDA-approved test; and
• adult and pediatric patients 12 years of age and older with advanced or metastatic RET fusion–positive thyroid cancer who require systemic therapy and who are radioactive iodine–refractory, if radioactive iodine is appropriate.a
aThis indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
Important safety information
• Interstitial lung disease (ILD)/pneumonitis: Severe, life-threatening, and fatal ILD/pneumonitis can occur in patients treated with pralsetinib. Pneumonitis occurred in 12% of patients who received pralsetinib, including 3.3% with grade 3 to 4, and 0.2% with fatal reactions. Monitor for pulmonary symptoms indicative of ILD/pneumonitis. Withhold pralsetinib 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 pralsetinib based on severity of confirmed ILD.
• Hypertension: Occurred in 35% of patients, including grade 3 hypertension in 18% of patients. Overall, 8% had their dose interrupted and 4.8% had their dose reduced for hypertension. Treatment-emergent hypertension was most commonly managed with antihypertensive medications. Do not initiate pralsetinib in patients with uncontrolled hypertension. Optimize blood pressure prior to initiating pralsetinib. Monitor blood pressure after one week, at least monthly thereafter and as clinically indicated. Initiate or adjust antihypertensive therapy as appropriate. Withhold, reduce dose or permanently discontinue pralsetinib based on the severity.
• Hepatotoxicity: Serious hepatic adverse reactions occurred in 1.5% of patients treated with pralsetinib. Increased aspartate aminotransferase (AST) occurred in 49% of patients, including grade 3 or 4 in 7% and increased alanine aminotransferase (ALT) occurred in 37% of patients, including grade 3 or 4 in 4.8%. The median time to first onset for increased AST was 15 days (range, five days to 2.5 years) and increased ALT was 24 days (range, seven days to 3.7 years). Monitor AST and ALT prior to initiating pralsetinib, every two weeks during the first three months, then monthly thereafter and as clinically indicated. Withhold, reduce dose or permanently discontinue pralsetinib based on severity.
• Hemorrhagic events: Serious, including fatal, hemorrhagic events can occur with pralsetinib. Grade ≥3 events occurred in 4.1% of patients treated with pralsetinib including one patient with a fatal hemorrhagic event. Permanently discontinue pralsetinib in patients with severe or life-threatening hemorrhage.
• Tumor lysis syndrome (TLS): Cases of TLS have been reported in patients with medullary thyroid carcinoma receiving pralsetinib. Patients may be at risk for TLS if they have rapidly growing tumors, a high tumor burden, renal dysfunction or dehydration. Closely monitor patients at risk, consider appropriate prophylaxis including hydration and treat as clinically indicated.
• Risk for impaired wound healing: Impaired wound healing can occur in patients who receive drugs that inhibit the vascular endothelial growth factor signaling pathway. Therefore, pralsetinib has the potential to adversely affect wound healing. Withhold pralsetinib for at least five days prior to elective surgery. Do not administer for at least two weeks following major surgery and until adequate wound healing. The safety of resumption of pralsetinib after resolution of wound healing complications has not been established.
• Embryo-fetal toxicity: Based on findings from animal studies and its mechanism of action, pralsetinib can cause fetal harm when administered to a pregnant patient. Advise pregnant patients of the potential risk to a fetus. Advise females of reproductive potential to use effective nonhormonal contraception during treatment with pralsetinib and for two weeks after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with pralsetinib and for one week after the last dose.
• Common adverse reactions (≥25%) were musculoskeletal pain, constipation, hypertension, diarrhea, fatigue, edema, pyrexia and cough. Common grade 3/4 laboratory abnormalities (≥2%) were decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased phosphate, decreased leukocytes, decreased sodium, increased AST, increased ALT, decreased calcium (corrected), decreased platelets, increased alkaline phosphatase, increased potassium, decreased potassium and increased bilirubin.
• Avoid coadministration of pralsetinib with strong or moderate CYP3A (cytochrome P450 3A) inhibitors, P-gp (P-glycoprotein) inhibitors, or combined P-gp and strong or moderate CYP3A inhibitors. If coadministration cannot be avoided, reduce the pralsetinib dose. Avoid coadministration of pralsetinib with strong or moderate CYP3A inducers. If coadministration cannot be avoided, increase the pralsetinib dose.
• Lactation: Advise patients not to breastfeed during treatment with pralsetinib and for one week after the last dose.
• Pediatric use: Monitor open growth plates in adolescent patients. Consider interrupting or discontinuing pralsetinib if abnormalities occur.
Side effects can be reported to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch, or to Genentech at 1-888-835-2555. The full prescribing information and patient information for pralsetinib can be found here.