FDA Meeting Workshop Transcripts With Fecal Transplant Doctors: More Regulation = Less Fecal Transplants

I found the transcripts from the FDA meetings in Bethesda, Maryland from May 2-3, 2013. Day 1 is here while Day 2 is here. If you add both documents it is over 600 pages. The first day wasn’t too interesting as it just the biology of fecal transplants and to be honest much of it I did not understand. The second day was more worthwhile because doctors who are actually performing fecal transplant presented what they have seen.  The second day included Dr. David Rubin, Dr. Lawrence Brandt, Dr. Colleen Kelly, Dr. Alexander Khoruts, and Dr. Hebert DuPont.

On the first day Dr. Allen-Vercoe creator of RePOOPulate from Canada only had two patients have done RePOOPulate and were saved by it as shown in this story. Canada is also much more friendly in terms in comparison to the FDA in regulating it as well. Actually RePOOPulate II is now being created and she is looking at it to treat IBD, obesity, and regressive autism.

Dr. Lawrence Brandt pointed out that the mortality rate of c difficile is 4% and jumps to 12% with a second infection of c difficile. The longest case he has had of c difficile has been 9 years.  For fecal transplants Dr. Brandt stops antibiotics (Dificid and Vancomycin) 2-3 days before the fecal transplant. Also Brandt reported the cure rate on fecal transplants is about 93% throughout the world.

Dr. Colleen Kelly reported that there are over 400 reported cases of fecal transplants in the literature however probably thousands performed (Dr. Borody as I pointed out here has done over 1,000 fecal transplants). She reports the success rate for fecal transplants after looking at 11 studies was 90%. To date Dr. Kelly has done 101 fecal transplants (ages 19-92). Of all these transplants 9 of them had inflammatory bowel disease. Kelly reports a 95% success rate. One patient that Kelly had who had ulcerative colitis (who I would point out was in his 70s) got a flare up after being off all his medications for 20 years. Kelly also pointed out that the labor required for one fecal transplant is equal to eight regular colonoscopies. On getting an Investigational New Drug (IND) (that the FDA grants) which she says was like learning a new language.  Dr. Kelly’s journey for the IND started in the fall of 2010 and wasn’t granted until 2012. In this process Kelly had to cancel 2 weeks of seeing patients and spend hundreds of hours working 12 hour days just to comply with the FDA to meet the IND.

Dr. David Rubin of University of Chicago mentions the FDA has been easy to work with yet challenging to work with at the same time. Rubin has been trying to study fecal transplants in ulcerative colitis patients.  He proposed it to his IRB (Institutional Review Board) who said they would give conditional approval but he still would need an IND.  Rubin had to submit a 206 page IND. The FDA had some suggestions and a new 168 page review was submitted.

Dr. Sachin Kunde who works on the pediatric side said that Mass General conducted a Phase I trial of looking at fecal transplants in IBD for children which lead to this study. Kunde discussed a study that looked at using enemas in pediatric patients with ulcerative colitis. What is interesting is close to 70% of patients had a clinical response by the end of the first month to the fecal transplant. Kunde in dealing with the FDA recommends hiring a study coordinator. Kunde’s IRB board also told her to stop what she was doing and get a IND from the FDA. She mentioned that the guidelines have been a challenge even after studying them for a year and a half.

Dr. Alexander Khoruts I learned is an advisor to CIPAC which is trying to commercialize full-spectrum microbiota for fecal transplants. Khourts’s first fecal transplant patient was a 61 year old woman who lost 40 pounds and having bowel movements every 15 minutes. Khoruts even had a patient who had c difficile for 12 years (recurrent infections). He also noted that IBD patients got better. In screening donors Khoruts uses a more rigorous approach then even the FDA (testing for more things, asking more questions, and is trying to standardize the donor process). Khourts himself spends an hour and half every day answering e-mails from c difficile patients.

Dr. Herbert DuPont who is prepared to set up a large fecal transplant program in Houston in association with the  University of Texas-Houston talked about the first fecal transplant he performed in 1970 (he is not a GI by training but an infectious disease doctor). DuPont who has been around a while talked about how things were done much more efficiently in the 1970’s when bureaucratic IRB boards were not around. No screening was done in those days. DuPont had a patent with severe antibiotic associated colitis and renal failure after a surgery. Vancomycin was used but didn’t work. DuPont then got immediate approval to do a fecal transplant. He used a blender and it was administered via retention enema to the patient. What is interesting is the donor was a typhoid carrier. However the patient who received the transplant did not get typhoid fever (it is hard to get typhoid fever from the rectum). In his transplant program DuPont wants to freeze the donor stool in order to standardize the procedure.

CEO Lee Jones of Rebiotix which plans to commercialize the fecal matter that can be used by doctors in fecal transplants. Jones has an IND for manufacturing, creating, and delivering the fecal material. The IND ran 1,500 pages. The company plans to have their product out by 2015 (assuming the FDA doesn’t delay this a few years).

Dr. Jay Slater who works for the FDA says the IND is hard yet very doable (too bad he doesn’t have to fill one out).  Doctors have told Slater how painful the experience of IND is and his response is “it’s definitely something that’s hard, it’s hard for a reason, and it’s very doable”. Also for an IND three phases are required just like for regular drugs.

The FDA is being overzealous as usual when it comes to fecal transplants. Fecal transplants have a cure rate of 90% with no serious adverse side effects (thousands have been performed). Filling out endless paperwork, constantly having to send the FDA data, and having meeting after meeting with the FDA doesn't help the patients truly in need of fecal transplants. With the new IND regulation fewer people will be able to get this life saving treatment and may possibly get worse and or die (which is pretty tragic). Dr. Kelly mentioned she spent hundreds of hours just simply trying to comply with the paperwork which is crazy. How on earth is the FDA going to regulate something they are not experts in? Having to go through three phases of clinical trials for fecal transplants will take many years (meanwhile people will be suffering). The doctors that have performed fecal transplants are the most knowledgeable on the whole procedure. A better way would be to have doctors who are performing them share their protocols and methods with each other in order to develop best practices.