The FDA has accepted the filing of a new drug application for surufatinib to be indicated as treatment of patients with advanced neuroendocrine tumors. The FDA set a Prescription Drug User Fee Act target action date of April 30, 2022.
The FDA has accepted the filing of a new drug application (NDA) for surufatinib (previously HMPL 012) to be indicated as treatment of patients with advanced neuroendocrine tumors (NETs). The FDA set a Prescription Drug User Fee Act target action date of April 30, 2022, according to a press release issued by the drug developer, HUTCHMED Limited.1
This consideration by the FDA follows a fast track designation granted to the agent in April 2020 for the treatment of pancreatic and extra-pancreatic NETs. Surufatinib also received orphan drug designation for the treatment of pancreatic NETs in November of 2019.
“This NDA filing acceptance of surufatinib in the U.S. is a significant achievement for HUTCHMED as we expand our global operations and work to bring our innovative oncology drugs to cancer patients worldwide. The FDA’s acceptance of the NDA highlights the clinical value of this submission package and the importance of bringing more treatment options to United States NET patients,” said Marek Kania, MD, MBA, managing director and chief medical officer of HUTCHMED, in a statement.
Data from both the SANET-ep (NCT02588170) and SANET-p (NCT02589821) clinical trials support the NDA for surufatinib as treatment of advanced NETs.
SANET-ep was a randomized, double-blind, placebo-controlled, phase 3 trial conducted in China in which patients with advanced extrapancreatic NETs were treated with surufatinib 300 mg versus matching placebo. A total of 198 patients were randomly assigned to receive either surufatinib (n = 129) or placebo (n=69). The study explored the primary end point of investigator-assessed progression-free survival (PFS) in the intention-to-treat population and it was predicted that the treatment would lead to PFS events in 70% of the patient population.2
At a median follow-up of 13.8 months (95% CI, 11.1–16.7) in the surufatinib group and 16.6 months (9.2–not calculable) in the placebo group, the investigator-assessed median PFS was 19.2 months (95% CI, 7.4–11.1) versus 3.8 months (3.7–5.7), respectively (HR, 0.33; 95% CI. 0.22–0.50; P < .0001).
Given that the PFS in the surufatinib arm was significantly longer than in the placebo arm, the study met the prespecified criteria for early termination. The efficacy results suggested that surufatinib may be a new treatment option for patients with advanced extrapancreatic NETs. Further, the agent had a good benefit-risk profile.
Grade 3 or higher treatment-related adverse events (TRAEs) in the surufatinib versus the placebo group were most commonly hypertension (36% vs. 13%, respectively) and proteinuria (19% vs. 0). Serios TRAEs were reported in 25% of the surufatinib compared with 13% of the placebo group. Of those treated with surufatinib, 3 experienced a treatment-related death as did 1 patient in the placebo arm.
In the multicenter, randomized, double-blind, placebo-controlled, phase 3 SANET-p trial, patients with advanced pancreatic NETs were treated with surufatinib 300 mg or matching placebo. These patients were evaluated for the same primary end point of investigator-assessed PFS.3
At a median follow-up of 9.3 months (95% CI, 9.3-19.4) in the surufatinib arm and 11.1 months (5.7-35.9) in the placebo group, the investigator-assessed PFS was 10.9 months (95% CI, 7.5-13.8) compared with 3.7 months (95% CI, 2.8-5.6), respectively, for an HR of 0.49 (95% CI, 0.32-0.76; P = .0011).
SANET-p was also terminated early due to the significant improvement in PFS observed with surufatinib and the tolerable safety profile of the agent as treatment of patients with advanced pancreatic NETs.
Hypertension was seen in 38% of the surufatinib arm versus 6% of the placebo arm, proteinuria in 10% versus 2%, respectively, and hypertriglyceridaemia in 7% versus none, respectively, were the most common grade 3 or higher TRAEs in the study. Serious TRAEs were seen in 2% of the surufatinib group compared with 7% of the placebo group, and there were 3 treatment-related deaths with surufatinib versus 1 with placebo.
An Expanded Access Protocol has since been initiated by HUTCHMED in the US to offer access to treatment for patients with NETs who have limited therapeutic options. The FDA cleared the protocol, and the program (NCT04814732) is now open.1
Along with the NDA being reviewed by the FDA, an application for regulatory approval was also submitted to the European Medicines Agency.
1. U.S. FDA accepts filing of HUTCHMED’s NDA for surufatinib for the treatment of advanced neuroendocrine tumors. News release. HUTCHMED Limited. July 1, 2021. Accessed July 1, 2021. https://bit.ly/365VmZQ
2. Xu J, Shen L, Zhou Z, et al. Surufatinib in advanced extrapancreatic neuroendocrine tumours (SANET-ep): a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2020;21(11): P1500-1512. doi: 10.1016/S1470-2045(20)30496-4
3. Xu J, Shen L, Bai C, et al. Surufatinib in advanced pancreatic neuroendocrine tumours (SANET-p): a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2020;21(11): P1489-1499. doi: 10.1016/S1470-2045(20)30493-9