Expanded Access: Not a Clinical Trial But….

This week, I attended CBI’s Expanded Access Programs conference in Philadelphia. First thing to note, early in the conference there was a discussion among the experts in the field about the terminology of expanded access. So right there, when you are talking about expanded access, early access, managed access, pre-approval access or and compassionate use, just be very clear on what your definition is. Even the FDA representative Richard Klein acknowledged he didn’t realize there was a terminology issue.

I was asked by an attendee why I was there, clinical trials editor in an expanded access world, which doesn’t have anything to do with clinical trials. Clinical trials and expanded access (which is the terminology I’m going with) are very different. The IND is held by a physician. The data requirements are nowhere near the rigor of a clinical trial. And patients comprise a wide swath outside of inclusion and exclusion criteria. But based on statements and observations at the conference, this list comprises why clinical trials professionals need to know about expanded access:

• Many of the now-dedicated EA managers were former clinical trial professionals.

• The questions of investigational drug supply need to be closely calculated with your clinical trial investigational drug supply.

• Operationally, clinical trials and expanded access programs are the same.

• Is there a potential to de-rail a clinical trial if expanded access is allowed? Klein said no, however, this past November a patient died in a CytRx compassionate use program, and the FDA put the program on hold. That hold was lifted in January. The definition of de-rail could be debated, as to some any delay in a trial can cost a lot of money.

• Planning for an expanded access program requires deep communication with others who know of the clinical successes of an investigational medicine in Phase I or II.

The rules of expanded access programs are quite clear. The FDA even launched a dedicated Expanded Access (Compassionate Use) website on Day 2 of the conference. The bottom line is that the sponsor has the ultimate decision if they are going to provide the drugs for expanded access programs or not. But with social media and internet transparency, coupled with the understandably heavy emotions that go along with life-threatening diseases, and the general mistrust of the biopharm industry, make a clearly defined regulatory guidance appear gray.

Which is exactly what happened to biotech Chimerix in April 2014. As detailed in this article from Bloomberg, Chimerix was inundated with far-flung social media support for Josh Hardy, a seven-year-old whose life-threatening disease could be treated with Chimerix’s drug in development. The Bloomberg article is an excellent in-depth presentation of both sides of the compassionate use debate, and brings the ethical decisions out to light. In the end, Josh received the drug, with a positive response, and CEO Kenneth Moch was forced out of his job.

But the message was clear: biotechs need to develop a clear policy on expanded access and have it in place to address just these types of instances. In October 2014, BIO released its

. The message at this conference was also clear. Attendees spanned biotech companies including AbbVie, Alexion, Biogen Idec, Celsion, Seattle Genetics, as well as big pharma Boehringer Ingelheim, all with varying phases of expanded access resources and experience. From those who need to think about offering their investigational drugs outside of a clinical trial, to those who have already been through the process a few times.

The motivation for a company’s established policy is to make it clear that when they do say no to a patient the reason why is transparent. But the motivation of the individuals-the professionals in pharma-is the patient.

Pfizer’s Expanded Access Lead, Business & Regional Operations presented on its three-year dedicated program. Erin Lambert, who is the lead, presented at CBI “Sustainable Strategies for Forecasting & Establishing Expanded Access Supply.” She came from drug supply and recounted to the audience the first time she was asked how they could get investigational drug directly to a patient. “That experience of being that close to the patient, that felt really good,” Lambert told the audience. And now their program “comes from the position of yes”--the position that they can make it happen for the patient.

Another attendee told me of her own stress levels after surpassing multiple barriers to finally, successfully getting the investigational drug to a patient and how emotionally spent she was afterward. The end result? She only knows that the woman lived long enough to receive her transplant two weeks later.

And that, I would say, is the final comparison between clinical trials and expanded use programs. There is not a lot of one-to-one interaction among pharma and its patients. But the dedication that clinical trial and biopharmaceutical professionals have to the people they are trying to help is evident.