A Phase 1, Single-Center, Double-Blind, Randomized, Placebo-Controlled Study to Explore the Effect of SP-624 on Brain Network Analytics in Cohorts of Healthy Adult Subjects and Subjects With Major Depressive Disorder

The main goal of this clinical trial is to learn if the active study drug (code name: SP-624) has any effect on the electrical activity of the brain in adult healthy volunteers and in adults with major depression. Another goal of the study is to learn if SP-624 improves memory and learning in adults with major depression. The study will also provide additional information on the safety of SP-624 and how well it is tolerated in adult healthy volunteers and adults with major depression.
Researchers will compare SP-624 to a placebo (a look-alike substance that contains no drug) to see if SP-624 has any effect on study tests.
Study participants will:
Take capsules of study drug (SP-624 or a placebo) once daily for 2 weeks; visit the clinic at Screening, Day 1 (first dose of study drug), and Day 15 (last dose of study drug) for checkups and tests; and have phone call check-ups on Day 7 and about 1 week after the last dose of study drug.

Start Date22 Aug 2024

Sponsor / Collaborator

Sirtsei Pharmaceuticals, Inc.

NCT06254612

/ CompletedPhase 2

A Multi-center, Double-Blind, Randomized, Placebo-Controlled Study of the Efficacy and Safety of SP-624 in the Treatment of Adults With Major Depressive Disorder

This is a Phase 2B clinical study evaluating the effectiveness and safety of SP-624 as compared to placebo in the treatment of adults with Major Depressive Disorder.

Start Date25 Mar 2024

Sponsor / Collaborator

Sirtsei Pharmaceuticals, Inc.

[+1]

NCT04510298

/ CompletedPhase 1

A Pilot, 4-Week, Randomized, Double-Blind, Placebo-Controlled, Inpatient, Multicenter Study of the Safety, Population Pharmacokinetics, and Exploratory Efficacy of SP-624 in Acutely Psychotic Adult Subjects With Schizophrenia

This is a Phase 1B clinical study evaluating the safety and exploring the effectiveness of SP-624 as compared to placebo in the treatment of adults with schizophrenia experiencing acute psychosis.

Start Date15 Oct 2020

Sponsor / Collaborator

Sirtsei Pharmaceuticals, Inc.

100 Clinical Results associated with Forvisirvat

100 Translational Medicine associated with Forvisirvat

100 Patents (Medical) associated with Forvisirvat

Literatures (Medical) associated with Forvisirvat

12 Mar 2026·ACS Medicinal Chemistry Letters

Lead Optimization: Synthesis and Biological Evaluation of Griseofulvin Derivatives as Novel SIRT6 Activators

Article

Author: Štefane, Bogdan ; Maraš, Nenad ; Ciber, Luka ; Novinec, Marko ; Kogovšek, Jan ; Ostojić, Ivana ; Zorko, Tilen

SIRT6, a crucial regulator of aging and cellular homeostasis, represents a promising target for small-molecule activation. In this study, we investigate griseofulvin and its derivatives as novel SIRT6 activators, focusing on the recently developed compound forvisirvat, which has progressed to Phase 2 clinical study. Biochemical evaluation revealed that griseofulvin itself possesses strong SIRT6-activating properties, achieving up to 10-fold activity at 100 μM. Modification of the griseofulvin scaffold generally led to reduced activity, prompting a focus on the oxadiazole moiety of forvisirvat. This strategy produced several analogues with higher potency, the most active at 100 μM being para-1,3,4-oxadiazolephenyl analog 21, which achieved 30-fold SIRT6 activation. Compounds bearing para-substituted phenyl rings exhibited excellent retention of activity at lower concentrations, with para-tolyl derivative 24 being the most potent at 10 μM. Retention of activity at pharmacologically relevant concentrations underscores their potential as potent SIRT6 activators and provides a rationale for continued development as drug candidates.

02 Sep 2025·CURRENT MEDICAL RESEARCH AND OPINION

A phase 2, multicenter, double-blind, randomized, placebo-controlled study of the safety and efficacy of forvisirvat (SP-624) in the treatment of adults with major depressive disorder

Article

Author: Rigdon, Greg ; Clayton, Anita H. ; Ackermann, Michael ; Kornstein, Susan G. ; Papakostas, George I. ; Raskin, Joel ; Hall, John ; Prescott, Yuki ; Wargin, William ; Abernathy, Kelly

OBJECTIVE:

Forvisirvat (SP-624), an orally-administered epigenetic sirtuin 6 (SIRT6) activator with antidepressant effects in animal models, was well tolerated in three phase 1 trials. This phase 2 study, SP-624-201, evaluated the safety and efficacy of forvisirvat 20 mg daily for 4 weeks in participants with major depressive disorder (MDD).

METHODS:

SP-624-201 (NCT04479852) was a double-blind, placebo-controlled study. Participants were adults who met DSM-5 criteria for moderate to severe MDD and who discontinued psychoactive medications or supplements including antidepressants and mood stabilizers. Primary endpoint was change from baseline to Week 4 in Montgomery Asberg Depression Rating Scale score. Participants were randomized to forvisirvat 20 mg daily (N = 163) or placebo (N = 156).

RESULTS:

Of the 317 treated patients, 224 (70.7%) were White and 211 (66.6%) were female. No significant difference in the primary endpoint was observed between treatment groups. However, post-hoc analysis found that women treated with forvisirvat experienced significant overall improvement whereas men did not. The difference between sexes was also consistent for secondary efficacy measures. No serious adverse events were reported for forvisirvat-treated participants. The most frequent treatment-emergent event was headache (forvisirvat: 8.1%, placebo: 11.5%). Six of 161 forvisirvat-treated participants and 5 of 156 participants who received placebo discontinued due to adverse events.

CONCLUSIONS:

The novel epigenetic mechanism of action of forvisirvat, favorable safety profile, and consistent post-hoc efficacy results in women observed in this study support further development of forvisirvat. A phase 2b/3 trial of forvisirvat in MDD (NCT06254612), to confirm these results, is ongoing.

01 Jan 2025·Clinical Pharmacology in Drug Development

Phase 1, Single‐Center, Double‐Blind, Randomized, Placebo‐Controlled Studies of the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Oral Doses of the Sirtuin 6 Activator SP‐624 in Healthy Adults

Article

Author: Greg Rigdon ; William Wargin ; Joel Raskin ; John Hall ; Kelly Abernathy ; Yuki Prescott

Abstract:

Sirtuin 6 activation is a novel epigenetic mechanism proposed for treatment of depression. Two Phase 1 studies, SP‐624‐101 and SP‐624‐102, examined the pharmacokinetics and safety of SP‐624, an orally active sirtuin 6 activator, in healthy adults. SP‐624‐101 was a single‐ascending‐dose study. In Part A, participants were randomized 6:2 to SP‐624 (single oral doses of 3, 10, or 30 mg) or placebo. Part B compared results in 8 participants receiving SP‐624 while fasting or after a high‐fat, high‐calorie breakfast. In SP‐624‐102, a multiple‐ascending‐dose study, participants were randomized 6:2 to SP‐624 (3 or 10 mg SP‐624 daily) or placebo for 5 days and 5:2 to SP‐624 20 mg daily or placebo for 10 days. At all doses, maximum concentration (Cmax) exceeded predicted target plasma concentrations of 3.28 ng/mL. Area under the concentration‐time curve and Cmax increased dose proportionally. A food effect resulted in significantly lower Cmax, later time to maximum concentration, and comparable AUC for fed versus fasting participants. No serious adverse events were observed. In SP‐624‐101 and SP‐624‐102, respectively, 3 (12%) and 5 (29%) SP‐624–treated participants experienced treatment‐emergent adverse events. SP‐624 was well tolerated and reached target concentrations in healthy adults, supporting progression of SP‐624 20 mg daily into Phase 2 studies of major depressive disorder.

News (Medical) associated with Forvisirvat

13 Aug 2026

·www.biospace.com

Arrivo Bio to Participate in Fireside Chat at the Piper Sandler Virtual CNS Symposium

MORRISVILLE, N.C.--(BUSINESS WIRE)--Arrivo Bio, a clinical-stage biopharmaceutical company developing first-of-its-kind medicines targeting the root cause of hard-to-treat diseases, today announced that Steve Butts, Co-founder and Chief Executive Officer, and Joel Raskin, Chief Medical Officer will participate in a virtual fireside chat discussing forvisirvat, the company’s novel potential treatment for major depressive disorder, at the Piper Sandler Virtual CNS Symposium on Friday, August 14 th at 10:30 a.m. ET. For additional details or to request access to the webcast, please contact your Piper Sandler representative. About Arrivo Bio Arrivo is developing first-of-its-kind medicines that target the root cause of hard-to-treat diseases with the goal of achieving meaningful outcomes for patients, allowing them to live longer, healthier lives. Arrivo has two clinical-stage pipeline candidates, Forvisirvat (SP-624) for major depressive disorder and RABI-767 for predicted severe acute pancreatitis. Arrivo is based in Morrisville, N.C., on the edge of Research Triangle Park. For more information, visit . Contacts Media: Maggie Turano Account Director, ICR Healthcare maggie.turano@icrhealthcare.com Investor: Brandon Weiner Senior Vice President, ICR Healthcare brandon.weiner@icrhealthcare.com

17 Jun 2026

·www.businesswire.com

Clinical Data on Arrivo Bio’s RABI-767 program to be presented at EPC 2026 Annual Meeting

MORRISVILLE, N.C.--(BUSINESS WIRE)--Clinical data on Arrivo Bio’s RABI-767 program will be presented at the 58th European Pancreatic Club (EPC)/International Association of Pancreatology (IAP) Annual Meeting, taking place June 24–27, 2026 in Istanbul, Turkey. The presentation will highlight RABI-767, a small molecule pancreatic lipase inhibitor in development for patients with predicted severe acute pancreatitis (SAP). RABI-767 is designed to inhibit pancreatic lipase activity and interrupt the cascade of fat necrosis associated with tissue injury, organ failure and mortality in SAP, a condition for which no approved therapies currently exist. RABI-767 received Fast Track Designation from the FDA in July 2024. Earlier clinical data presented at the 2025 American Pancreatic Association Annual Meeting, where the abstract was recognized as a “Poster of Distinction”, showed RABI-767 was well-tolerated in both healthy adults and patients with predicted SAP, with no adverse safety signals observed and early signs of efficacy seen among participants enrolled in the ongoing Phase 2 study to date. Presentation Details Session: Acute Pancreatitis Study Group – EPC/IAP 2026 Presenter: Timothy B. Gardner, M.D., M.S., Dartmouth Hitchcock Medical Center and RABI-767-201 Study Lead Investigator Presentation: RABI-767 Study Presentation Date/Time: Thursday, June 25, 2026, 2:00-2:15pm EEST Location: Galata Hall, Istanbul, Turkey For more about Arrivo Bio and RABI-767, visit www.arrivobio.com. About Arrivo Bio Arrivo is developing first-of-its-kind medicines that target the root cause of hard-to-treat diseases with the goal of achieving meaningful outcomes for patients, allowing them to live longer, healthier lives. Arrivo has two clinical-stage pipeline candidates, Forvisirvat (SP-624) for major depressive disorder and RABI-767 for predicted severe acute pancreatitis. Arrivo is based in Morrisville, N.C., on the edge of Research Triangle Park. For more information, visit www.arrivobio.com.

Phase 2Fast TrackClinical Result

26 May 2026

·www.businesswire.com

Arrivo Bio to Present Clinical Data on Forvisirvat at 2026 ASCP Annual Meeting

MORRISVILLE, N.C.--(BUSINESS WIRE)--Arrivo Bio will be giving both an oral and poster presentation at the 2026 American Society of Clinical Psychopharmacology (ASCP) Annual Meeting, taking place May 26–29 in Miami, Florida. The presentations will highlight Forvisirvat (SP-624), Arrivo’s first-in-class oral activator of the SIRT6 enzyme, currently in a Phase 2b/3 study for major depressive disorder, with data read out expected later this year. Prior Phase 2 data demonstrated a signal of efficacy in females with MDD, with additional preclinical and clinical findings supporting effects on neuroinflammation, neuroplasticity and cognition. Oral Presentation Details Presentation Title: Forvisirvat (SP-624), a First-In-Human SIRT6 Activator with an Epigenetic Mechanism of Action, Currently in a Phase 2b/3 Study for the Treatment of Major Depressive Disorder Presenter: Joel Raskin, MD, Chief Medical Officer Date/Time: Tuesday, May 26, 2:50pm to 3:00pm ET Location: Loews Miami Beach Hotel, Americana 3 Poster Presentation Details Poster Session: Pharmaceutical Pipeline Poster Number: T27 Presenter: Joel Raskin, MD, Chief Medical Officer Date/Time: Thursday, May 28, 11:30am to 1:15pm ET Location: Loews Miami Beach Hotel, Americana 4 For more about Arrivo and Forvisirvat, visit www.arrivobio.com. About Arrivo Bio Arrivo is developing first-of-its-kind medicines that target the root cause of hard-to-treat diseases with the goal of achieving meaningful outcomes for patients, allowing them to live longer, healthier lives. Arrivo has two clinical-stage pipeline candidates, Forvisirvat (SP-624) for major depressive disorder and RABI-767 for predicted severe acute pancreatitis. Arrivo is based in Morrisville, N.C., on the edge of Research Triangle Park. For more information, visit www.arrivobio.com.

Phase 2ASCOClinical Result

100 Deals associated with Forvisirvat

External Link

KEGG	Wiki	ATC	Drug Bank
D13109	-	-	-

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Depressive Disorder, Major	Phase 2	United States	Sirtsei Pharmaceuticals, Inc.	30 Sep 2020
Schizophrenia	Phase 1	United States	Sirtsei Pharmaceuticals, Inc.	15 Oct 2020

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04479852 (SP-624-201, CTgov)	Phase 2	Depressive Disorder, Major	319	SP-624 (SP-624)	vjkdzyoxgh(melbmigoqj) = jqszicmdzb bvyyydtyzw (glqesztppr, 0.83) View more	-	12 Jun 2025
				Placebo (Placebo)	vjkdzyoxgh(melbmigoqj) = flirlhtleu bvyyydtyzw (glqesztppr, 0.84) View more
NCT06570369 (SP-624-103, BusinessWire) Manual	Phase 2/3	Depressive Disorder, Major	12	SP-624	hmnpxsqsae(hnzlbxrati) = Subjects showed an increase in beta power, particularly in the frontal-central regions compared to patients taking placebo after a single dose, suggesting enhanced synaptic plasticity and neuronal connectivity. ghanqhwdgw (fazifuzorm ) View more	Positive	10 Jan 2025
				Placebo
NCT04479852 (Biospace) Manual	Phase 2	Depressive Disorder, Major	205	SP-624	twwzoqylyp(bllmbzuykp) = mcmmxjkewb ketlchgunv (avjgqzqilv ) View more	Positive	17 Oct 2022
				Placebo	-
NCT04479852 (Biospace) Manual	Phase 2	Depressive Disorder, Major	319	SP-624	ywqccynlik(eqsvsltiao): P-Value = 0.011 View more	Positive	17 Oct 2022
				Placebo

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