Has Response Pharmacauticals won the fight against antipsychotic weight gain?

The Virginia-based company has revealed promising results from its phase 1b clinical trial assessing RDX-002, a novel small molecule therapy designed to address this pressing medical concern.

The trial, conducted over two weeks, has yielded findings that emphasize the potential of RDX-002 in mitigating the adverse metabolic effects associated with antipsychotic medications, the company says.

Antipsychotic-induced weight gain is a well-documented phenomenon that poses a significant challenge in the management of mental illnesses such as schizophrenia, depression, and bipolar disorder.

These conditions often necessitate the use of antipsychotic medications to alleviate symptoms and improve patients' quality of life. However, a common side effect of many antipsychotics is rapid and clinically meaningful weight gain, which can occur within the first few weeks of treatment and persist over the long term.

This weight gain, Response says, not only leads to poor adherence to medication regimens but also contributes to the development of metabolic abnormalities such as hyperlipidemia and hyperglycemia, thereby increasing the risk of cardiovascular disease and diabetes.

Dr. Joseph Coyle, emeritus chair of psychiatry and neuroscience at Harvard Medical School, highlighted the significance of addressing AIWG.

Rapid weight gain and obesity

He said “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.”

In light of these challenges, Response Pharmaceuticals embarked on a clinical trial to evaluate the safety and efficacy of RDX-002, a first-in-class candidate treatment aimed at preventing the rapid weight gain associated with antipsychotic medications.

The phase 1b trial enrolled 24 healthy, antipsychotic-naïve volunteers who were initially treated with olanzapine, a widely used antipsychotic known for its propensity to induce weight gain.

During the trial, people were randomized to receive either RDX-002 in addition to olanzapine or olanzapine alone for the duration of the second week. The primary endpoint of the trial was to assess the impact of RDX-002 on postprandial triglycerides (ppTGs), a key marker of metabolic health.

The results, Response says, were striking, with subjects in the RDX-002 cohort demonstrating a remarkable 82% reduction in postprandial triglycerides compared to those receiving olanzapine alone.

Dr. Paul Sweetnam, chief science officer of Response Pharmaceuticals and lead inventor of RDX-002, elaborated on the implications of these findings, he said: “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.”

Reduction in weight gain

In addition to the favorable effects on postprandial triglycerides, the company said exploratory analyses revealed a notable reduction in weight gain among patients treated with RDX-002.

While patients receiving olanzapine alone experienced a significant increase in body weight during the first and second weeks of treatment, those receiving RDX-002 demonstrated minimal weight change, highlighting the potential of RDX-002 to mitigate the metabolic effects of antipsychotic medications.

Response Pharmaceuticals CEO Eric Keller is optimistic about the impact of RDX-002. He said: “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.”

The positive results from the phase 1b trial have paved the way for further clinical development of RDX-002. Response Pharmaceuticals is now preparing to initiate a phase 2 clinical trial to evaluate the efficacy of RDX-002 in patients with bipolar depression and schizophrenia initiating olanzapine therapy.

The trial, the company says, will be a placebo-controlled 12-week study designed to assess changes in weight gain and postprandial triglycerides, to further validate the potential of RDX-002 as a treatment for AIWG.

Antipsychotic-induced weight gain remains a significant unmet medical need, affecting millions of individuals worldwide. Response Pharmaceuticals' forward-thinking approach with RDX-002 aims to offer hope for improved outcomes and enhanced quality of life for patients grappling with this challenging side effect of antipsychotic medications.

As the company continues to advance its clinical development program, there is optimism that RDX-002 may emerge as a much-needed therapeutic option for individuals at risk of AIWG.