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OPNT: Encouraging Data From P1 Study of OPNT002 in Alcohol Use Disorder

07/19/2017
By David Bautz, PhD

OTC:OPNT

Business Update

Encouraging Results From a Phase 1 Development Study of OPNT002 

On July 19, 2017, Opiant Pharmaceuticals Inc. (OTC:OPNT) announced results from a Phase 1 study of OPNT002, an intranasally (IN) administered formulation of the opioid antagonist naltrexone hydrochloride. Opiant is developing OPNT002 for the treatment of Alcohol Use Disorder (AUD). The Phase 1 study examined the effects of Intravail® on the pharmacokinetic properties of IN naltrexone in healthy volunteers. A total of 14 men and women between the ages of 18 to 55 participated in the study. Each subject received four naltrexone treatments. 

Results from the study showed that Intravail® both increased the maximal plasma concentration (Cmax) of IN naltrexone and decreased the time to reach Cmax from 30 minutes to 10 minutes. The median time to reach Cmax following administration of IN naltrexone with Intravail® was also more rapid than an intramuscular (IM) injection of naltrexone. Oral administration of 50 mg of naltrexone resulted in a slower time to reach Cmax than either IN or IM administration. Importantly, the results with IN naltrexone seen without any identified safety or tolerability issues. There was also no evidence of nasal irritation.

To follow up on these results, Opiant has signed a contract manufacturing agreement with Renaissance to develop an IN naltrexone formulation for Phase 2 studies. The company has previously worked with Renaissance for commercial manufacturing of NARCAN® Nasal Spray.

Intravail®   

The Intravail® technology was developed by Aegis Therapeutics, LLC and comprises a broad class of chemically synthesizable transmucosal absorption enhancement agents to allow the intranasal (although other routes of administration are available including oral, rectal, ocular, etc.) administration of therapeutics up to 30,000 Daltons molecular weight. 

Intravail® excipients are members of a class of compounds known as alkylsaccharides, sugars that are covalently linked to one or more alkyl chains (Maggio et al., 2012). The following image shows a typical Intravail® alkylsaccharide structure, with sucrose and maltose as example saccharide moieties.

The excipients used in the Intravail® technology are safe to use. Following administration, the alkylsaccharides are quickly metabolized to the natural dietary components of a sugar and a fatty acid. The No Observed Effect Level (NOEL) for some of the excipients (sucrose esters) is as high as 2,000 mg/kg body weight (WHO, 1998), while the World Health Organization (WHO) oral allowable daily intake is approximately 10,000 times the amount used in a single nasal spray dose.
 
The effectiveness of alkylsaccharides in increasing transmucosal absorption is shown through an assay measuring the reduction in transepithelial electrical resistance  (TEER). The assay involves growing human tracheal and bronchoepithelial cells to confluence in culture, which results in tight junctions between cells that prevents the flow of ions when subjected to an electrical current. Thus, a reduction in TEER to ions flowing across the confluent cell layer is a way to measure openings in the tight junctions. The following graph shows the reduction in TEER that is seen for a number of alkylsaccharides used in the Intravail® technology along with those that are not. The Intravail® excipients show TEER decreases of close to 100%, while non-Intravail® alkylsaccharides are no more effective than saline (PBS). 

The opening of the tight junctions between cells is a reversible process, as shown in the following graphs. The “0 minutes” line indicates the pharmacokinetic profile for intranasal administration to rats of small proteins (calcitonin on the left and somatotropin on the right) along with an alkylsaccharide excipient. The next line shows the pharmacokinetic profile when the alkylsaccharide is separately administered intranasally to the animal followed 60 minutes later by the protein. The lower line shows the pharmacokinetic profile when the alkylsaccharide is administered 120 minutes before the protein. For the smaller molecule (calcitonin is 4 kDa), some absorption still takes place at the 60 and 120 minute mark following alkylsaccharide, although it is steadily decreasing with time. For the larger molecule (somatotropin is 22 kDa), no absorption is seen when it is administered 60 or 120 minutes after administration of the alkylsaccharide. In addition, these results show that the excipients work on the mucosal membrane, and not through direct interaction with the drugs being administered, since the alkylsaccharide can be administered separately and still result in absorption of the drug.

FDA Gives Supportive Feedback for OPNT002 in Alcohol Use Disorder

On February 28, 2017, Opiant announced that the U.S. Food and Drug Administration (FDA) gave supportive feedback from a Type B meeting in regards to the proposed development plan for OPNT002 for the treatment of AUD.

The SAMHSA 2015 National Survey on Drug Use and Health reported approximately 17.3 million people in the U.S. with alcohol dependence or abuse. There are three FDA approved medicines to treat alcohol dependence including Antabuse®, Vivitrol®, and Campral®. Vivitrol® is an extended release version of naltrexone that is administered by injection once monthly. Sales of Vivitrol totaled $209 million in 2016 ($110 million for AUD), and it is expected to generate approximately $300 million in revenue in AUD in 2022 (EvaluatePharma). OPNT002 is differentiated from Vivitrol® as it will be used on an “as needed” basis. 

Conclusion

Opiant appears to be on track with the development of OPNT002 for the treatment of AUD with the encouraging Phase 1 data showing increased absorption of intranasally administered naltrexone with the use of the Intravail® technology. We look forward to learning more about the Phase 2 program and believe that AUD represents a sizeable market opportunity for Opiant with potential peak revenues of approximately $200 million. 

In addition to AUD, Opiant is also targeting bulimia nervosa, for which it initiated a clinical trial earlier this year, and cocaine use disorder, each of which is a potential $300 million opportunity. Our currently valuation is $20 per share, and with a goal of uplisting later in 2017, now would be a good time for investors to take a closer look at Opiant. 

READ THE FULL RESEARCH REPORT HERE

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