MORRISVILLE, N.C.--(BUSINESS WIRE)--Arrivo BioVentures today announced preliminary results from its SP-624-201 study, a randomized, placebo-controlled Phase 2 clinical trial of SP-624 in 319 patients with major depressive disorder (MDD). SP-624 is a first-in-class, sirtuin 6 (SIRT6) activator being studied in patients with MDD. In the SP-624-201 study, patients who had inadequate or nonresponse to one treatment for the current depressive episode were given either SP-624 (20mg) or placebo orally once daily for 4 weeks. The trial results were not statistically significant on the primary endpoint, Montgomery-Asberg Depression Rating Scale (MADRS) score, for all study participants; however, in a post hoc analysis, females treated with SP-624 experienced statistically significant and clinically meaningful improvement in symptoms of depression.
Females represented two-thirds of the patients enrolled in the study, with 205 female patients contributing to the efficacy results. SP-624’s efficacy over placebo was measured after 1 week of treatment and increased each week during the 4-week treatment period, with statistically significant separation between active and placebo in female patients achieved as early as Week 3 on the MADRS score (p=0.011). After 4 weeks of treatment, the change from baseline on the MADRS score in female patients was significantly greater, with a 3.9-point reduction on the MADRS score compared to placebo (p=0.008). In addition, 25% of the female patients on SP-624 achieved remission (MADRS score ≤10) at Week 4 and 38% of female patients on SP-624 achieved a clinical response (defined as ≥50% reduction on the MADRS from baseline) at Week 4.
The results on the MADRS score were supported by consistent results on secondary efficacy endpoints in females, as SP‑624 achieved statistical significance on the CGI-S and HAM-D-17, both investigator-rated scales, as well as on the SDS and QIDS, two patient-rated measures. The impact of SP-624 appears durable, as one week following the last dose of study drug, female patients who had received SP-624 showed continuing statistically significant separation compared to those treated with placebo per MADRS and CGI-S (p<0.01). “While more studies are needed, based on its novel mechanism, early and increasing efficacy seen by both patients and investigators, along with the benign adverse event profile seen in the study, SP-624 has the potential to be an important new treatment for major depressive disorder,” said psychiatry consultant Joel Raskin MD, FRCPC.
SP-624 was well tolerated. The most common adverse events were headache and nausea, although they appeared more frequently in patients on placebo than in patients treated with SP-624. None of the study participants required a dose reduction due to tolerability issues.
In 2020, an estimated 21 million adults (about 8.4% of the population) in the U.S. had at least one major depressive episode.1 Females represent two-thirds of all patients currently being treated for depression.2 In addition, female patients are twice as likely than male patients to seek treatment for mental health conditions.3 "This is an important day for the study of depression in females. These results push the field beyond its current understanding of the disease, potentially opening new avenues for the treatment of specific patient populations,” said Steve Butts, CEO of Arrivo. “We look forward to unlocking the potential of SIRT6 activation to help millions of females struggling with depression and other conditions, starting with Phase 3 studies of SP-624 that are expected to commence in 2023.”
About the SP-624-201 Phase 2 Study
Study SP-624-201 was a multicenter, 4-week, double-blind, placebo-controlled, 2-arm safety and efficacy study in patients with MDD. Patients entering the study were required to have failed on one antidepressant in the current depressive episode. Patients were randomized on a 1:1 basis between 20mg of SP-624 and placebo. Patients were allowed to lower the dose if there were tolerability issues; however, all patients in the active arm remained on 20mg of SP-624. The primary endpoint was the change from baseline between the active and placebo arms at Week 4 on the MADRS. There were a number of secondary measures including the investigator-rated scales: Clinical Global Impression - Severity (CGI-S) and Hamilton Depression Rating Scale – 17 Item (HAMD-17); as well as patient-rated scales: Sheehan Disability Scale (SDS), Quick Inventory of Depressive Symptomatology – 16-Item, Self-Report (QIDS-SR16), and Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q). SP-624‘s efficacy was also measured at Week 5 (one week off drug) to evaluate whether the effects of SP-624 lasted beyond the discontinuation of dosing.
About Arrivo BioVentures, LLC
Working in partnership with investors, innovators, and pharmaceutical companies, Arrivo is always seeking solutions for unmet medical needs. Arrivo has built a portfolio of diverse drug candidates with the potential to be first-in-class or best-in-class.
Arrivo is founded and led by a team that has built and sold four companies in the last 15 years. Two products are currently commercially available and helping patients. Arrivo is propelled forward by its insatiable curiosity and drive to solve complex problems and help millions of patients globally.
Sirtsei Pharmaceuticals, Inc., a wholly owned subsidiary of Arrivo, holds exclusive worldwide rights (ex. Japan) to SP-624.
Arrivo is based in Morrisville, N.C., on the edge of Research Triangle Park. For more information, visit www.arrivobio.com.
- Front. Psychiatry 2021 12:589687.doi: 10.3389/fpsyt.2021.589687
- National Center for Health Statistics, National Health Interview Survey, 2020