LONDON – If the claim is true, then drug delivery has never been so exciting, or more profound. "We are rethinking psychiatry," said Richard Pops, CEO of Alkermes plc, giving an update on the portfolio at the company's R&D day.

The assertion rests on the way in which Alkermes' focus on taking tried and tested compounds and reformulating them to improve safety and efficacy has been applied to opioid drugs. That has enabled the company to open up the opioid system as the "super controller" that plays a key role in multiple psychiatric disorders, while modulating its influence to remove the potential for abuse and addiction that is a hallmark of existing opioid drugs.

Opioids as a class are highly validated. Alkermes' insight is that the way to unlock that potential is through understanding where and how those drugs have their effect, and then tune them accordingly. "Opioid receptors are G protein-coupled receptors and the science of GPCRs has advanced a lot in the past few years," noted Elliot Ehrich, chief medical officer. "Also the tools have evolved and you can look at receptor engagement."

Delving into the company's large opioid library to apply that knowledge, "we found that you can de-link addictive properties of opioids from the therapeutic opportunities," Ehrich said. The outputs are not typical me-toos with slightly preferable features, but new molecular entities (NMEs). As a result, Dublin-based Alkermes is moving from focussing on advanced formulations of existing drugs to generating NMEs that harness the power of the opioid system to treat serious chronic psychiatric disorders.

Given that the roll call here includes depression, pain, schizophrenia, bipolar disorder, obsessive-compulsive disorder and post-traumatic stress disorder, "rethinking psychiatry" may not be too extravagant a claim. "Opioids have beneficial effects, and we think you can have non-addictive opioid receptor modulators," Ehrich said.

Evidence for that comes from Phase II data on Alks 5461, released earlier this year, in the treatment of major depressive disorder in patients who have an inadequate response to treatment with selective serotonin reuptake inhibitors (SSRIs). The product is a fixed combination of buprenorphine, a partial agonist, and Alks 33, a mu-opioid antagonist designed by Alkermes to be non-addictive. Early clinical development of the drug was funded through a grant from the National Institute on Drug Abuse.

"The initial pharmacology shows [Alks 5461] fully blocks addictive effects, and in Phase II there were clear anti-depression effects," Ehrich said. In addition - and unlike SSRIs - Alks 5461 has a rapid onset of effect, hopefully avoiding suicidal feelings. There is "clear evidence" for advancing the product into Phase III development, and Alkermes is meeting the FDA shortly with the aim of starting the trial in 2014, Ehrich said.

Building further on that approach, Alkermes also announced at its recent R&D day that it is advancing Alks 3831, a combination of the approved antipsychotic drug olanzapine and Alks 33, into a 400-patient Phase II trial in schizophrenia. "We have designed Alks 3831 as a broad spectrum schizophrenia agent addressing two specific patient subpopulations: patients who may benefit from attenuation of the significant weight gain often associated with olanzapine treatment and patients with a dual diagnosis of substance abuse disorder, which often exacerbates their schizophrenia," Ehrich said.

During the R&D day, Alkermes also discussed the first data on Alks 7106, an opioid-based treatment for chronic pain. Preclinical research indicates the product is 30 times more potent than morphine. Whereas existing drugs continue to promote neurotransmitter release as the dose increases, Alks 7106 has a ceiling effect on neurotransmitter release over a broad concentration, indicating a low potential for abuse, according to Ehrich. The company will file an investigational new drug application with the aim of starting a Phase I study in mid-2014.

"We've done it; it's not theoretical. We have developed a deep understanding of new approaches to the opioid system," Ehrich said.

Pops reinforced that. "We are at a magic moment in the company's development where everything starts to gel," he said.

Alkermes is advancing valuable new medicines in chronic diseases with huge unmet need, working from known pharmacology. "We won't explore new pathways, but fine-tune [precedented] ones. We're not doing drug delivery anymore; we have transformed the scientific capabilities of the company," Pops said.