Rigel Pharmaceuticals Completes Transfer of GAVRETO® (pralsetinib) New Drug Application

GAVRETO will be available from Rigel in the U.S. beginning June 27, 2024

SOUTH SAN FRANCISCO, Calif., June 24, 2024 /PRNewswire/ -- Rigel Pharmaceuticals, Inc. ("Rigel") (Nasdaq: RIGL) today announced the completion of the transfer to Rigel of the New Drug Application (NDA) for GAVRETO^® (pralsetinib) for the treatment of adult patients with metastatic rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC) as detected by a U.S. Food and Drug Administration (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). GAVRETO will be commercially available from Rigel in the U.S. by prescription beginning June 27, 2024.

"The transfer of U.S. rights to GAVRETO has been completed and we are excited to announce that GAVRETO – a once-daily, oral targeted therapy for patients with RET fusion-positive mNSCLC and advanced thyroid cancer – will be available to patients from Rigel beginning this week. Our distributors, patient services, and field teams are ready and committed to ensuring both existing and new patients and providers can have access to this important treatment option without interruption," said Raul Rodriguez, Rigel's president and CEO. "The addition of GAVRETO to our commercial portfolio is another important step forward in our strategy to leverage our existing infrastructure and expertise to expand our hematology and oncology business."

GAVRETO's NSCLC indication is fully approved by the FDA and its advanced thyroid indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for the advanced thyroid indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). Discussions with the FDA regarding confirmatory requirements are ongoing.

GAVRETO is the only once daily, oral RET-inhibitor therapy that is designed to selectively target RET in mNSCLC and advanced or metastatic thyroid carcinoma. The recommended dosage of GAVRETO is 400 mg taken orally once daily. GAVRETO will be supplied as follows:

For those who qualify, Rigel offers patient assistance programs for patients prescribed GAVRETO by their doctor. RIGEL ONECARE^®, the company's comprehensive patient support center, can help patients and physicians as they navigate through insurance coverage requirements and provide financial assistance when needed and if eligible, along with other support programs. To learn more, visit www.RIGELONECARE.com or contact RIGEL ONECARE at 833-RIGELOC (833-744-3562).

Rigel announced its acquisition of the U.S. commercial rights of GAVRETO from Blueprint Medicines Corporation in February 2024.

About NSCLC
It is estimated that over 230,000 adults in the U.S. will be diagnosed with lung cancer in 2024.  Lung cancer is the leading cause of cancer death in the U.S, with NSCLC being the most common type accounting for 80-85% of all lung cancer diagnoses.¹ RET fusions are implicated in approximately 1-2% of patients with NSCLC.²

About GAVRETO^® (pralsetinib)

INDICATIONS

GAVRETO (pralsetinib) is indicated for the treatment of:

• Adult patients with metastatic rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC) as detected by an FDA-approved test
• 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 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 GAVRETO. Pneumonitis occurred in 12% of patients who received GAVRETO, including 3.3% with Grade 3-4, and 0.2% with fatal reactions. Monitor for pulmonary symptoms indicative of 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 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 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 1.5% of patients treated with GAVRETO. 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: 5 days to 2.5 years) and increased ALT was 24 days (range: 7 days to 3.7 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.
• Hemorrhagic Events: Serious, including fatal, hemorrhagic events can occur with GAVRETO. Grade ≥3 events occurred in 4.1% of patients treated with GAVRETO including one patient with a fatal hemorrhagic event. Permanently discontinue GAVRETO 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 GAVRETO. Patients may be at risk of 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 of Impaired Wound Healing: 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.
• Embryo-Fetal Toxicity: 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 last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with GAVRETO and for 1 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 aspartate aminotransferase (AST), increased alanine aminotransferase (ALT), decreased calcium (corrected), decreased platelets, increased alkaline phosphatase, increased potassium, decreased potassium, and increased bilirubin.
• Avoid coadministration of GAVRETO with strong or moderate CYP3A inhibitors, P-gp inhibitors, or combined P-gp and strong or moderate CYP3A inhibitors. If coadministration cannot be avoided, reduce the GAVRETO dose. Avoid coadministration of GAVRETO with strong or moderate CYP3A inducers. If coadministration cannot be avoided, increase the GAVRETO dose.
• Lactation: Advise women not to breastfeed during treatment with GAVRETO and for 1 week after the last dose.
• Pediatric Use: Monitor open growth plates in adolescent patients. Consider interrupting or discontinuing GAVRETO if abnormalities occur.

You may report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 

Please click here to see the full Prescribing Information and Patient Information for GAVRETO.

GAVRETO and RIGEL ONECARE are registered trademarks of Rigel Pharmaceuticals, Inc.

About Rigel
Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) is a biotechnology company dedicated to discovering, developing and providing novel therapies that significantly improve the lives of patients with hematologic disorders and cancer. Founded in 1996, Rigel is based in South San Francisco, California. For more information on Rigel, the Company's marketed products and pipeline of potential products, visit www.rigel.com.

1. The American Cancer Society. Key Statistics for Lung Cancer. Revised January 29, 2024. Accessed June 10, 2024: https://www.cancer.org/cancer/types/lung-cancer/about/key-statistics.html
2. Kato, S. et al. RET aberrations in diverse cancers: next-generation sequencing of 4,871 patients. Clin Cancer Res. 2017 April 15;23(8):1988-1997. doi: 10.1158/1078-0432.CCR-16-1679

Forward Looking Statements
This press release contains forward-looking statements relating to, among other things, the potential benefits of Rigel's acquisition of U.S. rights to GAVRETO, including opportunities in NSCLC and DTC, Rigel's ability to leverage its existing commercial infrastructure to market and distribute GAVRETO, provide patients with access to GAVRETO, and the market opportunity for GAVRETO. Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Forward-looking statements can be identified by words such as "plan", "potential", "may", "expects", "will" and similar expressions in reference to future periods. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based on Rigel's current beliefs, expectations, and assumptions and hence they inherently involve significant risks, uncertainties and changes in circumstances that are difficult to predict and many of which are outside of our control. Therefore, you should not rely on any of these forward-looking statements. Actual results and the timing of events could differ materially from those anticipated in such forward looking statements as a result of these risks and uncertainties, which include, without limitation, risks and uncertainties associated with the commercialization and marketing of GAVRETO; risks that the FDA or other regulatory authorities may make adverse decisions regarding GAVRETO; risks that GAVRETO may have unintended side effects, adverse reactions or incidents of misuses; the availability of resources to develop market and distribute GAVRETO; risks related to the transition of GAVRETO to Rigel, including risks related to the effectiveness of transition services and drug continuity; market competition for GAVRETO; as well as other risks detailed from time to time in Rigel's reports filed with the Securities and Exchange Commission, including its Quarterly Report on Form 10-Q for the quarter ended March 31, 2024 and subsequent filings. Any forward-looking statement made by us in this press release is based only on information currently available to us and speaks only as of the date on which it is made. Rigel does not undertake any obligation to update forward-looking statements, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise, and expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein, except as required by law.

Contact for Investors & Media:

Investors:
Rigel Pharmaceuticals, Inc.
650.624.1232
[email protected] 

Media:
David Rosen
Argot Partners
212.600.1902
[email protected]

SOURCE Rigel Pharmaceuticals, Inc.