And Then There Were Three!

A day after writing a post about abuse-deterrent products and their potential impact on patients, the generic drug industry and the FDA, the Agency approved the third opioid extended-release product with abuse-deterrent information in its labeling approved via a supplemental new drug application, the drug Embeda (morphine sulfate/naltrexone hydrochloride) Extended-release Capsules.  Embeda was originally approved in 2009, and the product was off the market from 2011 to 2013 while stability issues related to the manufacturing process were being addressed.

According to the FDA Press Release (here), “Embeda has properties that are expected to reduce, but not totally prevent, abuse of the drug when crushed and taken orally or snorted. Embeda works by releasing only the morphine in the capsule when taken properly. When crushed, the naltrexone in Embeda blocks some of the euphoric effects of the morphine and can precipitate withdrawal in persons dependent on opioids.”

FDA noted that, while the drug can still be abused by any method of abuse, “[A]dditional data from abuse liability studies conducted in laboratories and in people demonstrated the abuse-deterrent features of Embeda for certain types of abuse (oral and snorting), when the product was crushed. The abuse potential for the intravenous route was studied by simulating the amount of morphine and naltrexone that would be released upon crushing Embeda. This study demonstrated that Embeda was less attractive to abusers or less likely to produce a high (lower “Drug Liking” and “Drug High”) compared with morphine alone. However, it is unknown whether these results with simulated crushed Embeda predict a reduction in abuse by the intravenous route until additional postmarketing data are available.”

The Agency is still requiring post-marketing epidemiological studies of the product “to assess the effects of the abuse deterrent features of the product”.

The FDA’s Paragraph IV data base indicates that first-to-file applications for the following Embeda generic versions of the product were filed in 2010.

Morphine Sulfate and Naltrexone Hydrochloride

Extended-release Capsules

100 mg/4 mg

Embeda

5/3/2010

Morphine Sulfate and Naltrexone Hydrochloride

Extended-release Capsules

60 mg/2.4 mg

Embeda

5/25/2010

Morphine Sulfate and Naltrexone Hydrochloride

Extended-release Capsules

30 mg/1.2 mg, 50 mg/2 mg and 80 mg/3.2 mg

Embeda

5/28/2010

 

How this will impact those filings is not known.  Additional patents expiring in 2027 were listed in FDA’s Orange Book in 2011, but it is not known whether the approval of the new labeling supplement will lead to the submission of other patents.  What the Office of Generic Drugs does with these four-plus year old ANDAs should be watched closely by the industry.