Failure of AstraZeneca’s opioid drug trial a major blow for addiction medications: Report

New Delhi: The failure of the trial of the drug AZD4041 by pharma giant AstraZeneca, to combat opioid use disorder (OUD), highlights the challenges in developing non-opioid medications that treat addiction and withdrawal, according to a report on Wednesday.

OUD is a chronic neurological disorder that causes compulsive, repeated use of opioid drugs, leading to prolonged self-administration.

The company recently terminated the development of AZD4041 during a Phase II trial, as the orexin 1 receptor antagonist demonstrated a drug-drug interaction with an antifungal.

The report by GlobalData, a data and analytics company, showed that six out of the seven agents currently in late-stage development (Phases IIb–III) are non-opioids. It added that there is a distinct lack of efficacy data for the other pipeline agents.

“Opioid agonists dominate the treatment landscape for OUD, but their use is marked by a risk of “diversion” -- the illicit use of opioid medications -- meaning that their dispensing is often restricted to specialised treatment programmes,” said Jos Opdenakker, Pharma Analyst at GlobalData.

Opdenakker said these issues have led to a significant push in developing non-opioid medications to treat addiction and withdrawal.

Amid the tough competition from existing opioid medications, “finding a non-opioid to match their efficacy is proving to be challenging,” he added.

Further, the report said that non-opioid pipeline treatments are expected to enter the market as adjunctive treatments to the existing first-line therapies. Hence, they would not likely displace standard or care opioid treatments -- like methadone or buprenorphine -- as first-line treatments for OUD, the report said.

The report also forecasts that opioid agonist therapies could drive combined sales of approximately $1.75 billion by 2033 in eight major markets -- the US, France, Germany, Italy, Spain, the UK, Canada, and Australia -- and make up 83.8 per cent of the OUD market.

Such market dominance is emblematic of the lack of an effective alternative to opioid agonist therapies. It also shows patient preference, which plays a key role in OUD treatment.

“The OUD treatment landscape is bereft of an effective non-opioid therapy to challenge the existing opioid agonists. Although opioid agonists are the gold standard for the treatment of OUD, they have not been able to solve the opioid crisis,” Opdenakker said.

“Any non-opioid product that is able to reach the market with a strong efficacy and safety profile for the treatment of OUD would likely see strong uptake and will likely disrupt the OUD market,” he added.