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by Administrator | 21 Dec 2016

Rare autoimmune disease specialists shares his experiences

A conversation with Dr. Laurent Chiche

Late this past November, I had the opportunity to speak with Dr. Laurent Chiche about drug development in Europe. Dr. Laurent Chiche is a physician and researcher at the Hôpital Européen Marseille in France and is well-known for his work in immunology and rare diseases. Much of his current research centers around the Lupus Living Lab. In particular, we focused on the physicians’ experiences with using and/or getting regulatory approval for unregistered treatments in France.


Lisa Rebert: Have you ever considered using a non-registered treatment for a patient?


Dr. Laurent Chiche: Yes. For example, once I treated a teenager with an inflammatory eye disease. All other standard tear-drop treatments for this condition had been unsuccessful. After delving into the academic research, I found an animal model in mice that mimicked the condition that had a nice biologic treatment. In this case, we were able to obtain the drug for free from the pharmaceutical company. If the pharmaceutical company had not agreed to give us the drug for free, then the hospital would have had to pay these costs.

Once we had the drug, we made it into a tear-drop solution and tried it with the patient. The next step for us was to try and use this proof of concept to further the development of the drug. We tried to obtain an orphan designation for use of the drug for this disease indication, but because of the epidemiological debates about the disease they were targeting, it did not go forward. Therefore, we used the drug in a novel way, as tear-drops, but were ultimately unable to obtain larger approval.

So yes, we consider using orphan drugs and other drugs that are not available for typical indications. In the case I just mentioned, this drug is currently available in other forms and for a different disease, but it has never been used clinically in a tear-drop treatment. Using a drug with no indications is really uncommon, but off-label use is very common especially with rare diseases. I think it can also happen with more common diseases.


Lisa: What are the rules in France about doing what you just described above?


Dr. Chiche: When you do such things, you must have the approval of the hospital, a local ethics committee, an informed consent form from the patient, and include justification of the scientific rationale about why you want to use the drug in question. We can do almost anything when there is good scientific justification and no treatment alternatives.


Lisa: Can you describe how long this entire process typically takes?


Dr. Chiche: This is difficult to generalize because it depends on many parameters, such as: being in an academic/expert hospital; working with open-minded pharmacists; having access to the drug; the availability of sufficient data to support the scientific rationale; the agreement of all the medical staff; and the severity of the case (if it is urgent, things are easier).

That said, with the case of the inflammatory eye disease I’ve been discussing, it was not very difficult. From start to finish — i.e., getting the drug to the patient — only took three months. Yet I do not think this case is very representative. The longest part of the process for the eye disease related to obtaining the formula for a tear drop preparation from a team in the US who was performing an ongoing (unpublished) trial. After that, our pharmacists were able to prepare the formula and the local ethical and medical staff approvals went fast.


Lisa: Was the case you described for a rare disease or a non-rare disease?


Dr. Chiche: This was the problem, namely with the orphan drug designation. We did not have very good epidemiological data - therefore the EMA could not approve it. It was a debate for a few months where we had to prove it was indeed a rare disease. So, there was a high burden on us to prove that it was a rare disease.


Lisa: In your opinion, are other doctors and colleagues in France open to using drugs-in-development or off-label usage?


Dr. Chiche: Yes, I think so. However, there is often discussion between scientists in France over whether or not to try a new medicine as soon as it becomes available, but before widespread approval; and if so, with which patients. Current debate around a particular drug in France can be viewed as emblematic of what’s becoming a more common problematic with new drugs. Some scientists are pro and want to try it when there are no alternatives. Others are totally against this possibility because of weak scientific rationale. So that is the type of conversation we are currently having right now in France.


Lisa: What, from your direct experience as physician and researcher, would you like to see changed with the EMA drug approval process, especially for rare diseases?


Dr. Chiche: My feeling is that, most of the time, the EMA follows the decisions of the FDA. For rare diseases, I know a bit more. For instance, there was a biologic that was approved for the treatment of Lupus two years ago. Once the FDA ‘okayed’ it then the EMA decision did not differ except that — for cost reasons — they tried to reduce the target population to those most likely to respond.

I think it was a paradox to first say okay like the US, but then to find a way to reduce the target population on false scientific rationale. A lot of times the EMA won’t say no, but then they reduce the target population. This is not fair to patients.

For example, with this specific Lupus drug: France said yes to approving it so the costs are paid by the hospital, but in the UK it was not approved and therefore not available to patients there. Here in France, once the drug is approved, then the hospital is required to pay for it. So, I guess my overall critique would be that the EMA lacks in transparency and doesn’t fully take into account the differences between countries. Basically, at the end of the day the drug is approved, but you may not be able to obtain it in a specific country.



This is part one of a two-part interview series with Dr. Laurent Chiche. Here we focused on his personal examples of using unregistered treatments in France and the importance of scientific evidence. In the next segment, our conversations will delve deeper into Dr. Chiche’s current work with the Lupus Living Lab, the status of patient associations in France and the future of genetic technologies and rare diseases.

For more about Dr. Laurent Chiche, access his TedX Montpellier talk (in French) here.



Lisa Rebert (MPhil) is an aspiring science writer and the founder of Word Alchemists — a digital content creation and strategy firm that works with startups and nonprofits. Lisa has authored several articles and book chapters at the intersection of genetics, biomedicine, healthcare, and patient inclusion. Lisa is an independent writer and is not affiliated with myTomorrows, nor does she endorse myTomorrows.