Opiant Pharmaceuticals said this week it will launch a pivotal pharmacokinetics trial for its OPNT003 (nalmefene nasal spray) opioid overdose candidate in the second quarter—a key priority for the company this year, along with advancing its other pipeline candidates for opioid use disorder, alcohol use disorder, and acute cannabinoid overdose.

The study is expected to generate pivotal PK data in the second half of this year, Opiant disclosed in an investor presentation—data that the company hopes will be positive enough to underpin an NDA filing to the FDA planned for 2020, and entailing a combination of the drug and an intranasal delivery device.

“The reason why we believe this to be an important development is because of the changing nature of the opioid crisis,” Opiant CEO Roger Crystal, MD, told GEN recently.

That crisis, Crystal said, has evolved into a fentanyl crisis: 55% of the 49,000 opioid overdose deaths in 2017, according to provisional CDC data,  now involve fentanyl, the synthetic opioid which is longer acting and 50 times more potent than heroin, as well as 50 to 100 times more potent than morphine.

Resuscitating patients who overdose on fentanyl would require more naloxone, the nasal spray version of which the company developed, and won FDA approval in November 2015. That drug is now marketed as Narcan® Nasal Spray (naloxone HCl) by commercial partner Adapt Pharma—which was acquired last year by Emergent BioSolutions for up to $735 million.

Yet Narcan is harder for addicts to use in the roughly 70% of the U.S. that consists of rural areas, where access to EMS services may be delayed.

Crystal says Opiant could address those issues through OPNT003, which is five times stronger than Narcan. OPNT003’s 5-fold higher affinity to mu-opioid receptors is intended to be more effective at reversing fentanyl overdoses. The company also cites Phase I PK data showing that OPNT003 had a half-life of 6.7 to 7.8 hours, versus 1–2 hours for Narcan.

In addition to nalmefene, OPNT003 contains Intravail, a proprietary absorption enhancer designed to deliver rapid increases in nalmefene plasma levels. Opiant inked an exclusive global license of undisclosed value in 2017 to use Intravail with all opioid antagonists.

Abbreviated approval pathway

Opiant says it plans to develop OPNT003 under the FDA’s 505(b)2 abbreviated approval pathway, similar to Narcan. Under 505(b)2, companies can submit an NDA containing full reports investigating the safety and effectiveness of a drug candidate, but at least some of the information required for approval comes from studies not conducted by or for the applicant, and for which the applicant has not obtained a right of reference or use, according to an October 2017 FDA draft guidance.

Narcan is expected to generate between $220 million and $250 million in net sales this year, according to guidance from Emergent. If Emergent is correct, Opiant can expect a one-time milestone of $13.5 million in royalties based on net sales above $200 million in one calendar year. Narcan is also expected to generate an annual royalty stream of approximately $18 million to $21 million.

Nalmefene was approved as an injection drug for opioid overdose by the FDA in 1995 under the name Reveo® (Baxter International) and discontinued by the company in 2008. The injection form was also approved for reduction of alcohol dependence in adults by the European Commission in 2013 under the name Selincro® (H. Lundbeck).

“There’s never been a better time to really look at follow-on and further innovation in the area of overdose,” Crystal said. “At the NIH [Director] Francis Collins [MD, PhD] and Nora Volkow [MD, director of the NIH’s National Institute on Drug Abuse or NIDA] have been calling for longer-lasting and stronger opioid overdose reversible agents. That is very much what we believe this drug, nasal nalmefene, has the potential to do.”

NIDA awarded a $7.4 million grant to Opiant in April 2018 toward the development of OPNT003 as a long-lasting opioid antagonist for the treatment of opioid overdose. The grant included approximately $2.6 million to be funded for the period ending March 31, 2019, with the rest to be funded over the subsequent two years.

To cover activities not funded by NIDA—namely accelerating OPNT003’s development as a medical countermeasure in the event of a fentanyl chemical attack—the U.S. Biomedical Advanced Research and Development Authority (BARDA) last year awarded the company a multi-year contract for up to $4.6 million in funding.

Crackdowns on prescription opioids and heroin were linked in a study published in December 2018 to greater availability of fentanyl, which was implicated in nearly 29,000 overdose deaths in the U.S. in 2017.

“The issue around fentanyl and other derivatives, such as CA-fentanyl, is that they could be made very cheaply. They could be made in a lab. You don’t need the opium poppy. And it doesn’t take much to do a huge amount of harm,” Crystal said.

“A lot on our plate”

Beyond OPNT003, Opiant’s anti-opioid pipeline includes two preclinical opioid use disorder candidates—OPNT005 (heroin vaccine: hapten+liposome adjuvant) and OPNT006 (opioid antagonist implant).

Crystal said Opiant this year is also preparing to enroll patients into a Phase II study for its alcohol use disorder candidate OPNT002 (opioid antagonist nasal spray), and advancing development of its preclinical acute cannabinoid overdose (ACO) candidate OPNT004 (drinabant), for which the company has acquired global development and commercialization rights from Sanofi in December at a relative bargain price.

In its presentation, Opiant said it will reformulate drinabant for “parenteral administration that can rapidly reverse the symptoms of ACO in an emergency setting,” as well as “demonstrate the ability of drinabant to reverse the effects of THC.”

Opiant’s investor presentation came nearly a month after the company halted development of naloxone nasal spray, under the name OPNT001, in bulimia nervosa after the candidate failed a British Phase II trial last month.

The trial missed its primary endpoint of a reduction in binge eating days, Opiant acknowledged on February 21, without disclosing details. The study was launched in 2017 and in September 2018 completed enrollment of 86 patients across 19 clinical sites in the U.K.

“Quite frankly, we have a lot on our plate regardless,” Crystal said.

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