Satsuma Pharmaceuticals, Inc. announced the results of Phase 3 clinical studies for STS101, which are the long-term safety study (Study Name: ASCEND) and the efficacy study (Study Name: SUMMIT), on September 20, 2022 and November 14, 2022, respectively. SNBL would like to comment and add supplementary explanations of these results as well as the future NDA submission. The ASCEND study, a multi-center and open-label Phase 3 study for STS101, was designed to assess the tolerability and safety of STS101_5.2 mg in the acute treatment of migraine attacks over 6 and 12 months, in more than 450 subjects.

The primary endpoint was to evaluate the tolerability and safety of STS101_5.2 mg, and the secondary endpoint was to evaluate the efficacy of STS101_5.2 mg. In the ASCEND study, which incorporated an improved second-generation nasal delivery device, a total of more than 6,900 doses of STS101 were administered to more than 340 subjects. As for the results of the ASCEND study, although mild and transient treatment-emergent nasal adverse events of STS101_5.2 mg were reported, STS101_5.2 mg was well tolerated and safe for long-term use.

In addition, favorable efficacy results from the 172 subjects such as freedom from pain (Pain Free) by 2 hours post-treatment was achieved in 34.2% of all treated attacks, and freedom from most- bothersome-symptoms (MBS Free) from among photophobia, phonophobia and nausea by 2 hours post-treatment was achieved in 53.4% of all treated attacks. The SUMMIT study, a randomized, double-blind, placebo-controlled study for STS101, was designed to assess the efficacy of a single dose of STS101_5.2 mg (incorporated the second-generation nasal delivery device) in the acute treatment of migraine in more than 1,400 subjects. In accordance with the U.S. Food and Drug Administration's (FDA) Guidance for the Development of Drugs for the Treatment of Acute Migraine, the co-primary endpoints for STS101_5.2 mg, Pain Free and MBS Free at 2 hours post-dose, were statistically evaluated in comparison with placebo.

In addition, based on the guidance, secondary endpoints including Pain Relief at 2 hours post-dose and the requirement for other migraine rescue medications at 24 and 48 hours post-dose were also statistically compared with placebo. Pain Free and MBS Free at 2 hours post- dose for STS101_5.2 mg did not have statistically significant differences from those for placebo. One of the reasons for this result may be the high response rate in the placebo group (17.5% Pain Free and 32.9% MBS Free).

In phase 3 efficacy studies of other drugs for acute treatment of migraine (oral drugs), the response rates for placebo of Pain Free at 2 hours post-dose were reported to be 11.8 to 14.3%, which is relatively lower than that of the SUMMIT study. Assumption is that STS101 may have increased the expectation of the subjects, resulting in a relatively higher response for placebo during the earlier period after administration. On the other hand, STS101_5.2 mg demonstrated statistically significant effect on both Pain Free and MBS Free at 3 hours post-dose and at all subsequent timepoints versus placebo.

The results show that STS101_5.2 mg enables consistent and long lasting Pain Free and MBS Free. Additionally, the effect of STS101_5.2mg on Pain Relief, one of the secondary endpoints, was statistically significantly higher than that of placebo at 2 hours after administration, indicating that STS101_5.2mg enables relief from pain even in the early post-administration period. Furthermore, the effect of STS101_5.2 mg was statistically superior to placebo regarding the proportion of subjects requiring rescue medications to control migraine symptoms within 48 hours post-dose, showing that STS101_5.2 mg can reliably reduce migraine symptoms for a long time without additional rescue medications.

Therefore, although the co-primary endpoints were not achieved in the SUMMIT study, STS101 did reliably and consistently improve migraine symptoms for a long period of time without recurrence.