FDA Approval Sought for Pralsetinib in RET+ Medullary Thyroid Cancer

"Pralsetinib has broad potential to address the medical needs of patients with RET-altered cancers, who have not traditionally benefited from targeted therapy even though their tumors have a known disease driver."

A New Drug Application (NDA) was submitted to the FDA for pralsetinib (BLU-667) for approval consideration as treatment of patients with advanced or metastatic RET-mutant medullary thyroid cancer (MTC) and RET fusion–positive thyroid cancers.1

"Pralsetinib has broad potential to address the medical needs of patients with RET-altered cancers, who have not traditionally benefited from targeted therapy even though their tumors have a known disease driver," said Andy Boral, MD, PhD, chief medical officer at Blueprint Medicines, in a statement. "There are now pending marketing applications for pralsetinib in RET-altered non-small cell lung cancer and thyroid cancers, supporting our goal to advance treatment standards for these patients. We are working closely with the FDA and aim to bring this promising treatment to patients as expeditiously as possible."

Pralsetinib, an investigational inhibitor of RET fusions and mutations, recently demonstrated promise in a cohort of 13 patients with RET fusion–positive MTC in the phase 1/2 ARROW study (NCT03037385) of pralsetinib in patients with select RET fusion–positive solid tumors.

The MTC cohort achieved an objective response rate (ORR) of 74% in the treatment-naïve patients and an ORR of 60% in patients who had previous treatment. The disease control rate (DCR) observed with pralsetinib in patients with RET fusion–positive thyroid cancers was 100% (95% CI, 72%-100%). The best response was a partial response (PR), which was achieved in 91% of patients. Additionally, stable disease was observed in 9 patients and no patients had progressive disease.

During a presentation of the ARROW trial held during the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program,2 lead author Vivek Subbiah, MD, associate professor, Department of Investigational Cancer Therapeutics and Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, stated, “this shows that pralsetinib is active and the treatment benefit is prolonged in these patients with RET fusion–positive thyroid cancer. The responses were rapid, within 2 to 3 months of initiating treatment and pralsetinib was active post radioactive iodine.”

Notably, one 66-year old male patient with differentiated thyroid cancer had a favorable outcome with pralsetinib treatment. He achieved a deep and durable PR that lasted 18 months, and also had a 94% shrinkage of target lesions.

The safety analysis for the thyroid population showed consistency with the overall study population for which data were presented separately during ASCO 2020. Most of the adverse events (AEs) were grade 1 or 2 in severity. Treatment-related AEs were observed in 15% of the population and of them, the most frequent were anemia (33%), increased aminotransferase (33%), decreased white blood cell count (33%), hypertension (30%), increased alanine aminotransferase (26%), hyperphosphatemia (19%), and neutropenia (19%). No patients discontinued treatment as a result of AEs.

Overall, pralsetinib showed antitumor activity in RET fusion–positive thyroid cancer and across multiple solid tumors and was well tolerated in patients. The ARROW study is ongoing and is actively enrolling patients.

The NDA for pralsetinib will be reviewed under the Real-Time Oncology Review pilot program, which was designed by the FDA’s Oncology Center of Excellence to review approval applications more efficiently.

In addition to MTC, Blueprint Medicines, Inc, the developer of pralsetinib is also seeking approval for pralsetinib as treatment of locally advanced or metastatic RET fusion–positive non–small cell lung cancer. The application for this indication was accepted by the FDA in May 2020 and was granted a priority review; an application is also being validated by the European Medicines Agency. The FDA target action date for the lung cancer indication is November 23, 2020.


Blueprint Medicines announces submission of New Drug Application to FDA for pralsetinib for the treatment of advanced ret mutant and ret fusion-positive thyroid cancers. News release. Blueprint Medicines, Inc. July 1, 2020. Accessed July 1, 2020. https://bit.ly/2NJXn4z

Subbiah V, Hu MH, Gainor JF, et al. Clinical activity of the RET inhibitor pralsetinib (BLU-667) in patients with RET fusion+ solid tumors. J Clin Oncol. 2020: 38 (suppl; abstr 109). doi: 10.1200/JCO.2020.38.15_suppl.109

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