Surufatinib Granted FDA Orphan Drug Designation for Treatment of NETs

Surufatinib (HMPL-012) has been granted FDA Orphan Drug Designation for the treatment of pancreatic neuroendocrine tumors (NETs), according to a press release from Hutchison China MediTech Limited (Chi-Med).¹

Phase Ib/II data published inClinical Cancer Researchin March of 2019 showed that the study of surufatinib led to antitumor activity in patients with histologically advanced well-differentiated, low or intermittent grade, inoperable or metastatic NETs.²

In patients with pancreatic NETs, the overall response rate (ORR) was 19% (95% CI, 9—34). Patients with extrapancreatic NETs had ORR of 15% (95% CI, 6–31). Additionally, the disease control rate in these patients was 91% (95% CI, 77–97) and 92% (95% CI, 79–98), respectively. The median PFS was 21.2 months in patients with pancreatic NETs and 13.4 months in those with extrapancreatic NETs, (95% CI, 7.6–19.3).

Surafatinib was also considered to have a manageable toxicity profile. There were some grade ≥3 adverse events (AEs) observed. The most common AEs were hypertension (33%), proteinuria (12%), hyperuricemia (10%), hypertriglyceridemia, and diarrhea (6% for each), as well as increased alanine aminotransferase (5%).

“NET is an area of significant unmet medical need. The current treatment options are very limited,” said Christian Hogg, CEO of Chi-Med. “The FDA granting Orphan designation is a positive step and continues to reinforce the importance of our research and development in bringing surufatinib to more patients in need.”

Patients in the study were randomized to with 300mg surufatnib once daily or an equivalent dosage of placebo. Both treatments were administered on a 28-day cycle. The primary end point of the study was PFS, and the objective response rate, DCR, duration of response, time to response, overall survival and AEs were all assessed as secondary end points.

To enroll in the trial, patients were required to have radiological documentation of progression of disease within 12 months prior to randomization, measurable lesions, and a performance status of 0 or 1. Patients also required an absolute neutrophil count of &ge;1.5&times;109/L, platelet count of &ge;100&times;109/L, and hemoglobin &ge;9 g/dL; and serum total bilirubin <1.5 times the upper limit of normal (ULN). Patients could not have progressed on any more than 2 types of systemic therapies.

Individuals with grade 3 or higher neuroendocrine cancer, adenocarcinoma, pancreatic islet cell carcinoma, goblet cell carcinoid, large cell neuroendocrine carcinoma and small cell carcinoma, were excluded. The study also excluded patients with neuroendocrine tumors with pancreatic origins, as well the presence of gastrointestinal disease, serious hemorrhage, and other malignancies diagnosed within that past 5 years.

The novel angio-immuno kinase inhibitor is currently being studied in clinical trials across multiple solid tumor malignancies, in both U.S. and China.

Surufatinib inhibits tyrosine kinase activity associated with VEGFR and FGFR. The drug is the second novel agent developed by Chi-Med. In June of 2019, Chi-Med announced that the phase III SANET-ep study met the predefined primary end point of progression-free survival (PFS). Chi-Med then started the process for a pre-New Drug Application with the China National Medical Products Administration.³

References

1. Chi-Med Announces Surufatinib Granted FDA Orphan Drug Designation for Pancreatic Neuroendocrine Tumors [press release]. London, England: Hutchison China MediTech Limited; November 25, 2019. https://bit.ly/34smY92. Accessed November 25, 2019.
2. Xu J, Li J, Bai C, et al. Surufatinib in Advanced Well-Differentiated Neuroendocrine Tumors: A Multicenter, Single-Arm, Open-Label, Phase Ib/II Trial.Clin Cancer Res. June 15 2019 (25) (12) 3486-3494; DOI: 10.1158/1078-0432.CCR-18-2994.
3. Chi-Med Reports 2019 Interim Results and Provides Updates on Key Clinical Programs [press release]. London, England: Hutchison China MediTech Limited; July 30. 2019. https://bloom.bg/2OM9wGj. Accessed November 25, 2019.