Apadaz: The Best Case Scenario for FDA Labeling & Approval

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BACKGROUND WISDOM

(Ticker: KMPH) KemPharm, Inc filed an NDA for KP201/APAP in September of last year with an expected decision date on or around February 23rd, 2018.

KP201/APAP is an immediate release (IR) combination product of KP201 + APAP; better known by its trade name of Apadaz. Apadaz is intended for the short term management of acute pain.

APAP is just another name for acetaminophen (aka paracetamol), the active ingredient found in Tylenol, another kind of pain reliever.

As for KP201, this is a chemical called benzhydrocodone hydrochloride, and it’s a prodrug of hydrocodone. Hydrocodone is an opioid/narcotic that is often abused.

The fact that KP201 is a prodrug means that it is an inactive chemical that doesn’t become a functional pain reliever until it is activated by the body’s biochemical processes. Specifically, Apadaz is converted into an active drug via digestive enzymes, proteins that speed up biochemical reactions, found in the intestinal tract.

KEMPHARM MUST MAKE THE CASE

Crushing, grinding, smoking, or vaporizing Apadaz will not release the active hydrocodone. This helps deter the product’s abuse. Other than its potential ability to deter abuse, Apadaz is basically no different than similar products out on the market, such as Norco. This means, from a therapeutic/side-effect perspective, it has no real advantage over well-established competitors.

Ergo, KemPharm must prove to the FDA that Apadaz’s formulation does, in fact, deter its own abuse. If KemPharm succeeds in doing so, it can put abuse-deterrent language on its product label. This will give it a huge competitive advantage as doctors will choose to prescribe it over its well-established, but non-abuse-deterrent, competitors.

If KemPharm fails to prove this, then it’s basically all over.

WHY THE FDA REJECTED APADAZ

Given the opioid abuse crisis in the country, the FDA has acknowledged the need for such abuse-deterrent pain relievers. It even granted Apadaz priority review status in early 2016.

Several months later an FDA advisory panel (FAP) agreed, by majority decision, that Apadaz was an effective pain reliever. Nevertheless, the FAP did not believe that Apadaz deters abuse in any significant way; again by a majority decision.

At least on the point of abuse-deterrence, the FDA agreed with the advisory panel’s decision and issued a complete response letter (CRL) in mid-2016 and thus failed to approve the drug.

KemPharm appealed the decision but their appeal was unsuccessful. Nevertheless, an amended NDA was submitted and accepted with an approval decision date of February 23rd, 2018.

Overall, the main issues that KemPharm needed to address were whether or not Apadaz actually deterred abuse and should be labeled as an abuse-deterrent as a result.

We say this carefully, as press-releases are not always truthful nor fully forthcoming on all of the problems raised in a CRL. There may have been other concerns behind the FDA’s decision as well, such as some (relatively minor) safety concerns specific to Apadaz’s unique make-up.

From hereon, we examine KemPharm’s arguments for receiving abuse-deterrent labeling as well as how likely it is that they have the goods, scientifically speaking, to warrant FDA abuse-deterrent approval the second time around.

CATEGORY 1 LABELING

Let’s start with category 1 labeling; that of abuse-deterring chemical and physical properties that minimize the risk of intravenous (IV) abuse. This category utilizes lab-based studies that test the ease by which a chemical can be manipulated in a way that promotes drug abuse.

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Published: 2/9/2018

Updated on: 2/15/2018 – the article’s content was not altered; only the article disclaimer was modified on this date.

No one associated with this article has any financial stake in, or ties to, KMPH.

2018-12-05T16:13:00+00:00