#abuse deterrence

Is Egalet Corp (NASDAQ:EGLT) A Discount Entry On Its FDA Delay?

One thing we love to do here at Market Exclusive is to highlight potential discount entries in the biotech space. There is so much market inefficiency based around interpretation and misinterpretation of data releases and news updates, that these discount entries crop up quite regularly, and are there for the taking with the right timing. Of course, they don’t always play out, but when they do,…

INDIVIOR PLC SPON ADR EA REPR 5 ORD (OTCMKTS:INVVY) is up more than 11% on its Wednesday open on the company releasing data from its phase III in substance abuse. The trial is looking at an opioid abuse deterrent candidate, a subcutaneous injection formulation of an already approved drug called buprenorphine. We know Indivior is capable of Executing on a strong commercial rollout, based on the success of its Suboxone product, so if approved, this substance abuse drug has the potential to bring in a fresh wave of revenues for the company. Here is a look at the drug in question, and what the data tells us about the chances of approval.

So, as mentioned, it’s a reformulation of buprenorphine. Buprenorphine is a commonly prescribed opioid used primarily used as an opioid abuse drug (although sometimes used in low doses for pain management). What we mean by this is it is administered as an alternative to opioids in patients that have become dependent on other opioid drugs. It is generally issued as a combination with another abuse related drug, naloxone. Think of it as a sort of methadone alternative. It is designed to help wean patients off the stronger and more addictive opioid compounds. The regimen is an established treatment, but the current formulation requires daily dosing, and this has a couple of issues. First, it can be difficult for patients to maintain a daily dosing schedule, especially as part of a recovery program. Second, it is open to abuse. When treating high risk abuse patients such as those looking to get off stronger opioids, a prescription of buprenorphine can a) be abused itself or b) serve as gateway to a relapse.

Indivior’s answer to the problem is this subcutaneous injection version. It is a long-lasting, extended-release version of buprenorphine, designed to last 30 days from a one time administration. The advantages of this are clear –  it increases the chance of patient adherence to the dosing schedule (reducing administration days from 365 to 12) and pretty much closes off any chance of buprenorphine abuse or buprenorphine related relapse. If a patient only injects once a month, there is no need for them to take a prescription for the drug, and this limits access.

The trial in question was set up to assess RBP-6000’s, the drug in question, ability to counter abuse. The primary endpoint was the cumulative distribution function (CDF) of the percentage of urine samples negative for opioids combined with self-reports negative for illicit opioid use.  This sounds pretty complicated, but it’s not really. Essentially the company took urine samples at various points during the trial in patients that had taken either the drug or a placebo, and sampled them for opioid presence. The goal was to show that fewer patients in the active arm went on to use opioids during the trial than did patients in the control arm.

From the data we have (full analysis is not complete yet) the trial met this criteria, as well as a host of secondary endpoints, and the drug looks good for approval when the company submits a new drug application (NDA). Of course, nothing is certain, but there weren’t any safety and tolerability issues and from what we can see, and efficacy looks sound. Indivior  expects to put out a full analysis before the end of the first quarter of next year, and subsequently submit a new drug application to the FDA shortly thereafter. The agency has already granted fast-track review to RBP-6000, based on the drug meeting a currently unmet need (for an abuse deterrent opioid abuse treatment), which means assuming everything went smoothly, the agency should complete its review within six months of accepting the application. This paves the way for a marketing authorization by the end of next year, and gives us a few key milestones to focus on across the next 12 to 18 months.

These are as follows.

First, complete analysis and topline release. First quarter 2017. Second, NDA submission and subsequent acceptance. Second quarter 2017. Third and finally, PDUFA. Fourth-quarter 2017.

IntelliPharmaCeutics Intl Inc (USA) (NASDAQ:IPCI) is a tiny Canadian biotech with a market capitalization of a little over $40 million at last count. It generates virtually no revenues, and its entire cash holding derives from a $5.2 million public offering that closed at the beginning of last month. It’s down close to 20% on its 2016 open, and 56% on last year’s highs. That’s the bad. The good is this: it’s got an extended release oxycodone candidate that doesn’t need a phase III data to qualify for an NDA submission, and that submission is expected next month. If the FDA approves the application, it’s lead candidate, Rexista XR, will target a $2.3 billion extended release oxycodone market, in which the two currently approved options lack one or more of the features Rexista XR exhibits.

In short, it’s an extremely risky allocation, but with a very large potential upside if the stars align in the company’s favor. IntelliPharmaCeutics just offered an update as to a couple of key loose ends in advance of the August filing. Here’s what’s important, and what to watch going forward.

The update covered two points, with one relating to the drug and the other relating to the application. We’ll address the former first.

The drug, Rexista, is based on a system called the Novel Point Of Divergence Drug Delivery System (NPODDS). It’s pretty much exactly what it sounds like – on administration a drug has an immediate (but limited) loading dose that acts as a initial response to whatever pain it’s targeting. Beyond that, a second load doses, but this one is a steady, sustained release dose. It’s also got a host of abuse deterrent features. It coagulates if crushed and mixed with water, so it can’t be injected. It’s really tough to vaporize without what’s called pyrolization, which is essentially the decomposing of the active oxycodone ingredient. If you grind it with a goal of snorting or chewing it, it releases a blue dye that stains the entry point. It has a low reactive response to alcohol, which helps to avoid dose dumping. There are a few more, but these are the key points. It’s both quick and extended release, and it is really tough to abuse.

The most interesting point is this, however. The drug’s pathway to approval is based on a system called 505(B)(2). There are essentially three ways a drug can go from discovery to market – 505(b)(1) NDA, 505(b)(2) NDA and 505(j) ANDA. The latter is for generic drugs. The first is the standard process (discovery, sponsor conducts phase I, II and III, etc. Rexista’s pathway, 505(b)(2) NDA, is applicable when the drug in question is based on a combination of drugs already deemed safe and effective, and it can rely on data already produced to form the basis of an NDA. The update we are looking at covered the completion of what is essentially the only extensive data IntelliPharmaCeutics has had to produce itself, proof of concept aside, and it relates to the impact of food on Rexista’s efficacy. The result, there is none, which gives it an advantage over Xtampza, one of the drugs that Rexista will be competing against.

The second point relates to a waiver of the costs associated with the NDA submission. These are called user fees, and came about with the introduction of the PDUFA back in 1992. The cost for a submission like the one IntelliPharmaCeutics is putting forward is $1,187,100 for 2016, up a little bit on last year’s fee of $1,167,600. There are four different waiver categories – public health, barrier to innovation, financial considerations (these are mainly reductions rather than waivers) and small business. Given its size and revenues, IntelliPharmaCeutics qualifies for the last one, small business, meaning the FDA will waive its NDA submission fee.

So what are we looking for going forward?

The submission of the FDA should be the next major catalyst, and while there’s no guarantee that the company will hit its target, IntelliPharmaCeutics expects a submission during August this year. Beyond that, PDUFA should come relatively quickly, given the nature of the application. Again, to reiterate, this is a really risky allocation. Financially the company is at the very low end of what’s acceptable. From an opportunity perspective, however, it’s well worth a look as a possible small speculative play.

EDIT: This article initially stated that IntelliPharmaCeutics has no approved products. The company has two approved products, details of which can be found below:

February 24, 2016 press release announcing the FDA approval of 500mg & 750mg Generic Keppra XR: http://www.intellipharmaceutics.com/releasedetail.cfm?ReleaseID=957022

November 18, 2013 press release announcing the FDA approval of 15mg and 30mg Generic Focalin XR: http://www.intellipharmaceutics.com/releasedetail.cfm?ReleaseID=808159