Thursday, November 10, 2011

Compassionate Use Drug Availability for ALS Patients

Time to wade into the water on a controversial topic, Compassionate Use Drug authorization for ALS Patients.

This topic has been discussed extensively for some time on the message boards and social media sites. Terminally ill patients with little to lose want access to whatever is available that has shown safety and efficacy and potential upside as soon as possible. Every day and minute counts.

Most clinical trials run 12-15 years from conception to shelf. Only one drug is approved for ALS treatment today and is marginally effective. All the new announcements of discoveries we see today will ultimately yield some hypothesis in labs. A few of those will begin that 12-15 years cycle at some point noted above and the cycle continues. Some promising drugs may already be in that 12-15 year pipeline at a middle or even latter stage and the cycle continues.

On the one hand you have pALS that are ineligible for these studies. Diagnosis more than 2-3 years prior, Functional Ratings Scale not at a certain point, or Respiratory Readings below the required reading are common disqualifiers.

On other hand you have pALS that are qualified to participate in Clinical Trials. All of them are double blind placebo based, the longtime industry standard. By definition, only half of the patients actually receive the drug that do participate. The Phase 2 or 3 study finishes recruitment and runs the required 12-18 months AFTER the LAST patient is enrolled. They then usually need 6-12 months to interpret the data and at least another year to get FDA approval and something potentially to shelf. Total elapsed time estimated from start to finish for this portion is 2-5 years. (Does 2-5 years ring a bell with anyone here?).

You get the picture. It's no wonder that ANYTHING currently showing promise stirs up interest in the pALS community for Compassionate Use.

Dexpramipexole (KNS-760704) is now 14+ years from the time the drug was discovered as a theoretical treatment. As is common with many other biotechs and pharmas, current owner Biogen Idec entered the process on this particular drug only recently.

The recent ALS TDI conference was extremely informative and featured some industry insiders discussing the state of ALS Research from a business perspective. It was very topical and George Scangros (CEO of Biogen Idec) was one of the participants. During the Q&A, a caregiver speaking on behalf of a pALS who could not speak, ask a key question to Mr. Scangros. He stated that he was ineligible for the DexPra Clinical Trial currently being conducted. "Was there a way to obtain compassionate use availability of the DexPra Drug for pALS outside the trial?," he asked. George said that they had considered it. But...Biogen felt the best way to get to a final decision on whether they could move the drug forward to the FDA was to focus all their resources toward the 800 current enrollees and the 400 additional pALS they are now enrolling." BOOM. No follow up question from the audience. Only a vague timeline of 12 months from now they will have the last patients full readings, then another 6-12 months to interpret the data, then another year or so to get FDA approval. This poor guy, and any of the rest of us pALS listening basically were told TOUGH LUCK FOR AT LEAST 2-5 YEARS (2-5 Years ring a bell?).

I am not naive. George runs a large biotech company that answers to shareholders. Biogen is a $4 Billion Fortune 500 company that threw off over $1 Billion in Net Income in 2010. They have stated they are committed to ALS Research. God knows we need more profitable companies like this supporting finding treatments and a potential cure. The capitalistic nature of drug development absolutely motivated these guys to make this investment after Knopp's trials showed promise. Biogen wants to bring this to market on a broadscale level to maximize their Return on Investment. I GET THAT.

Biogen's website states "To our partners and investors, we are a profitable company with a rich and diverse pipeline. We have the resources, financial strength and vision to successfully discover, develop, manufacture and commercialize new products. And to our friends, neighbors and the world at large, we are a responsible corporate citizen with robust programs that make our communities better places to live and work and address critical issues like diversity and sustainability. Biogen Idec is all these companies. We are dedicated to serving all our constituents, because Biogen Idec is in business to make a difference for all those we serve. Addressing patient needs is our core responsibility and defines our corporate citizenship. We updated our Code of Business Conduct to include additional guidance on critical issues, such as workplace health, responsible marketing and ethics in clinical research."

Two things need to occur with Dex, Fast Track Status Application and Compassionate Use Application. I assume the former is in process, and the latter has not occurred.

Regarding Fast Track Status, the FDA Division of Drug Information says to be eligible for the fast track program, a sponsor must first submit a request for fast track designation with supporting documentation for the product and its proposed use. Only when such a request has been formally submitted can FDA consider whether the conditions for fast track designation have been met (in brief, fast track designation can be granted for a drug to treat a serious or life-threatening disease if it is considered to fulfill an unmet medical need). If fast track designation is granted, the development of the drug may be expedited in certain ways. For a drug to be FDA approved, the sponsor must submit a New Drug Application (NDA) with data from clinical trials supporting the safety and effectiveness of the drug. For those drugs granted fast track designation, the Agency works closely with the sponsor to determine the most efficient development path for the drug, given that all drugs must be found to be safe and effective before they can be approved. It is sometimes also possible that drugs not yet approved may be made available to patients under special provisions of the law while the review of an NDA is on-going. Whether these provisions will apply in a given case will depend upon the data submitted by the sponsor, as well as other circumstances.

Regarding Compassionate Use, it's a common misperception in the ALS community that the FDA decides who gets compassionate use exceptions in totality. That is only part true. The first thing that needs to occur is the drug company has to APPLY. I would like to ask Biogen to review the statements italicized above and call for them to at least APPLY. Apply to the FDA for a compassionate use exception for pALS like my friend in the room at the ALS TDI conference that could not speak for himself. The data they have espoused over the past year to gain pALS, Investor and Industry support states this a safe, promising and potentially effective treatment option for pALS in the offing. While I am sure it would cost them some money to provide the drug to the pALS on a Compassionate Use level, it would in no way jeopardize their ability to complete the clinical trials and move through the required process.

In the near term, there are other hopefully effective treatments in the pipeline that pALS should encourage to do the same. To my knowledge Cephalon, with the drug Myotrophin (IGF-1), was about the only company in the past (over 15 years ago) that I am aware of that has even bothered to apply for a compassionate use exception with the FDA. These companies all walk a tightrope on bringing tomorrow's promise to patients today, ahead of the established curve. I GET THAT. BUT WE PATIENTS HAVE NOTHING TO LOSE AND TIME IS OUR ENEMY. Many of them, like Cephalon, are companies with shoestring budgets that are barely holding on to be able to run the existing trials in process. Money will almost certainly play a big role in their ability to offer Compassionate Use in the future. If they go out of business, it will not matter how promising the drug unless someone else acquires or invest in them. That's an unfortunate reality within the system today.

The system also continually asks pALS to participate in Clinical trials today that have almost zero probability to help us as individuals. But we do it to help others because it's the right thing to do.

Biogen is different from almost all the other companies noted above because they have the ability to help patients now. They have the money ($1 Billion in Net Income last year alone) and resources to step up and provide compassionate use of the drug today. If we are to believe all the hype, and the investors are to believe all the hype, then this is a no brainer. BIOGEN PLEASE STEP UP AND APPLY FOR COMPASSIONATE USE FOR DEXPRAMIPEXOLE TODAY.