FALLS CHURCH, Va.--(BUSINESS WIRE)--Response Pharmaceuticals, Inc., a clinical stage company focused on weight management and metabolic health in high-risk populations, today announced positive topline results from its Phase 1b clinical trial evaluating the safety and efficacy of RDX-002, a first-in-class candidate treatment for the prevention of the rapid weight gain associated with the leading antipsychotic medications. Antipsychotic-induced weight gain (AIWG) is a drug-induced epidemic within the already vulnerable population of patients with severe mental illness, including schizophrenia, depression and bipolar disorder, with patients experiencing rapid increases in body weight, hyperlipidemia and hyperglycemia.
“Antipsychotic medications are essential treatments that help millions of patients live better lives, but can be associated with rapid weight gain and obesity. This often leads to poor adherence to treatment and reduced quality of life, and contributes to long term cardiometabolic morbidities including decreased life expectancy” explained Joseph T. Coyle, MD, Emeritus Chair of Psychiatry and Neuroscience at Harvard Medical School. “The results of this trial suggest that RDX-002 may provide a unique therapeutic solution to address AIWG and the adverse metabolic changes that are associated with this weight gain.”
In the 2-week open-label trial, 24 healthy, antipsychotic-naïve volunteers were initially treated for 1 week with olanzapine, a highly efficacious antipsychotic, usage of which is associated with AIWG. Subjects were randomized at the outset of the study to either add RDX-002 orally twice a day to OLAN, or continue on OLAN alone during week two. Subjects in the RDX-002 cohort met the primary endpoint for efficacy, lowering postprandial triglycerides (ppTGs). In an exploratory analysis of AIWG, subjects receiving OLAN alone saw significant weight gain during the first and second weeks of treatment whereas there was no significant weight change in the RDX-002 cohort in week 2.
Subjects receiving olanzapine treatment showed a 54% increase in mean AUC postprandial triglycerides on Day 8 vs Day 1 (p=0.009) and remained elevated on Day 15. The olanzapine/RDX-002 cohort saw a decrease of 81.6% (p<0.001) in mean AUC ppTG on Day 15 vs Day 8. Overall RDX-002 was well-tolerated, with adverse events restricted to mostly mild to moderate GI effects, with no serious adverse events or treatment-related discontinuation during the study.
In exploratory analyses, OLAN alone resulted in a mean increase in body weight of 1.6 kg (2.1%) (p<0.001 vs Day 1) in the first week of treatment and an additional 1.7 kg (2.2%) (p=0.016 vs Day 8) in the second week. Subjects receiving RDX-002 in the second week saw only a 0.4 kg increase (p=0.443 vs Day 8). Additionally, subjects in the OLAN-only group in the second week saw an increase in LDLc of 24.8% (p=0.016), while subjects receiving RDX-002 experienced and increase of 4.3% (p=NS). While exploratory, these findings support results seen in other trials where RDX-002 has demonstrated an impact on body weight, hyperlipidemia and hyperglycemia.
“This study provides the first clinical evidence of increased post-prandial lipids with antipsychotic medications, suggesting upregulation in iMTP from antipsychotics may play a role in the rapid weight gain associated with these medications” said Response Pharmaceuticals Chief Science Officer and lead inventor of RDX-002 Dr. Paul Sweetnam. “Treatment with the iMTP-inhibitor RDX-002 significantly reduced ppTGs and blunted the weight gain in OLAN-treated subjects indicating a potential role in the treatment and prevention of AIWG. We expect to be presenting our detailed data set at an upcoming medical conference and in a scientific publication.”
“This is very promising news for patients who have long fought to manage not only severe mental illness, but also the syndrome of AIWG and its associated morbidities. This early evidence feeds our drive to help patients around the world, including the approximately 58 million Americans suffering from mental illness according to the NIH,” said Response Pharmaceuticals CEO Eric Keller. “Response is actively engaged in preparing for next-stage clinical trials in AIWG, as well as development into other indications suited to the metabolic impact of the unique iMTP mechanism of action of RDX-002.”
The planned Phase 2 clinical trial of RDX-002 will be a placebo-controlled 12-week study assessing weight gain and postprandial triglyceride changes in patients initiating olanzapine therapy for bipolar depression and schizophrenia. Response Pharmaceuticals is currently in the Series B funding stage.
About Antipsychotic-Induced Weight Gain
Antipsychotic-Induced Weight Gain affects millions of people worldwide. While current antipsychotic medications, such as olanzapine, quetiapine and clozapine, have been transformational for patients’ lives, a frequent side effect associated with these treatments is rapid, clinically meaningful weight gain, often occurring in the first few weeks of treatment and sometimes continuing for years. This results in high rates of medication discontinuation or a change to a less efficacious medication, and often leads to relapse and hospitalization. Along with clinically meaningful weight gain, atypical antipsychotics are known to cause other serious effects, including elevated serum triglycerides, increased LDL cholesterol, and blood sugar, each of which contribute to an increased risk of cardiovascular disease and diabetes, resulting in higher mortality rates and up to 17.5 years’ reduced life expectancy.
About the Study
The Phase 1B study was a single-center, open-label 15-day study in 24 healthy volunteers receiving OLAN. During the first week of treatment all subjects received OLAN alone and were randomized to either remain on OLAN alone or OLAN+RDX-002 during the second week of treatment. The primary endpoint was postprandial (pp)TG AUC measured on Day 1 (pre-OLAN), Day 8 and Day 15 after consumption of a meal standardized for total and fat calorie content. Secondary and exploratory endpoints included changes in fasting lipids and body weight as well as OLAN PK and safety.
About RDX-002
RDX-002, Response Pharmaceuticals’ lead candidate, is a first-in-class, potent, selective, and gut-specific small molecule inhibitor of microsomal triglyceride transfer protein (MTP). The overall effect of MTP inhibition is a decrease in the amount of triglycerides and cholesterol delivered to the body after a meal. RDX-002 has been studied in multiple Phase 1 and Phase 2 clinical trials including 496 healthy subjects and patients dosed for up to 84 days. In these studies, RDX-002 lowered post-prandial triglyceride levels, circulating levels of low-density lipoprotein cholesterol (LDLc), and reduced weight. RDX-002 is being developed as an adjunctive therapy for patients taking atypical antipsychotic therapy, as well as a potential treatment in other settings in which clinically significant weight gain and/or adverse metabolic changes are prevalent. RDX-002 is being developed under an exclusive world-wide license from Sanofi S.A.
About Response Pharmaceuticals
Response Pharmaceuticals is a clinical-stage biotechnology company focused on developing treatments for weight management and metabolic health in high-need patient populations. The company is building its portfolio with an initial focus on helping those taking antipsychotic medications for disabling mental illnesses to combat weight gain and metabolic dysregulation associated with these treatments. For more information, please visit https://www.responsepharmaceuticals.com.
