By Dana Yamashita

Mental health disorders are among the most common causes of disability. And good mental health is essential for maintaining family and interpersonal relationships, the ability to hold a job and contribute to community or society, and for maintaining good physical health.

Although schizophrenia is a relatively rare disorder, and varies among individuals, its effect on those diagnosed with the condition can be both severe and disabling. Not as uncommon, it is estimated that bipolar I disorder affects about 2.8% of the U.S. population. Together, the two disorders affect more than 8.5 million people in the U.S. Now, a new chemical entity discovered at Rensselaer Polytechnic Institute may help treat patients with these disorders.

It was in the lab of Mark Wentland, a medicinal chemist and now professor emeritus of chemistry and chemical biology at Rensselaer, that samidorphan was discovered. This new chemical entity, combined with the current antipsychotic drug olanzapine, can now be used to treat patients with schizophrenia and bipolar I disorder.

“Ever since my second year in college, I wanted to use my love of chemistry to improve human health. So I went into drug research thinking that’s how I could contribute,” Wentland said. “Schizophrenia and bipolar I disorder are dreadful diseases. It’s gratifying to know that our work may help people manage them effectively.”

The new drug, called LYBALVI, will be launched by pharmaceutical company Alkermes plc (“Alkermes”) in the fourth quarter of 2021. According to Alkermes, the combination of samidorphan and olanzapine demonstrated statistically significantly less weight gain than prescribing just olanzapine in patients with schizophrenia, which is one of the more common side effects.

With funding from the National Institutes of Health, Wentland led a team of medicinal chemists at Rensselaer whose goal was to synthesize long-acting, once-daily oral medications to treat opioid and cocaine use disorders. Biological testing of new compounds was done at the University of Rochester under the expert guidance of collaborator Jean Bidlack. From this collective effort, samidorphan emerged as a promising drug candidate.

“The development of samidorphan as a biologically stable mitigator of olanzapine side effects resulted from the careful, inspired application of years of medicinal chemistry experience by Professor Mark Wentland and his collaborators,” said Curt Breneman, dean of the Rensselaer School of Science. “Now his discoveries are positioned to directly help a great many people living with serious mental illness.”

With the aid of what is now the Rensselaer Office of Intellectual Property Optimization (IPO), the compounds were patented and licensed to Alkermes, which invested the resources to develop the compound library and ultimately carry LYBALVI through clinical trials.

“This has been an incredible milestone for Rensselaer,” said Bruce Hunter, executive director of the IPO. “Our work in technology transfer to actively support the movement of innovations and discoveries from the lab to the marketplace is focused on real-world solutions that uplift the human condition.”