Sarepta Therapeutics

I've talked about Sarepta here and here. I've talked about RNA drugs often. Here and here for example. In 2006 Jim Cramer of Mad Money was touting a biotech company that later tanked because one of the many pluses was their RNAi program. RNA drugs replaced the DNA drug projects that had failed miserably the decade before. RNA soon began suffering from the same issues as the DNA drugs, efficacy in the human body. Along the way however there was a Nobel Prize for its discoverers and wild investments that followed. The mania to turn this science into a pharmaceutical product, asap, stems from a fundamental misunderstanding of how a specific cell produces just the right amount of a specific protein to participate in the function of the entire living organism. Those who attempt to throw a little more nucleic acid into the body and hope that it cure diseases are grossly underestimating the complexity of our DNA.

I look at it like a view from an airplane flying out of LAX. You look down and find Venice Beach. You know where the sand hits the water but you can't make it out from that distance. It's the mile high view obscuring details. In the case of looking down at a cell from a microscope, we can't see DNA. We can see the nucleus but we can't make out the details of the DNA inside. We have learned a great amount and harnessed that knowledge to now be able clone genes, sequence DNA and so on. But we can't actually watch the things that take place with our DNA that regulate protein expression. Just as I can't make out where the sand reaches the water from my seat in the airplane, I can't see the protein expression machinery in action. I take a pipette and add some RNA to a cell culture and often times measure something other than the expression of the protein I'm trying to knock out. Now just imagine adding some RNA to a human body and measuring something like a miniscule effect in very sick people like those suffering from Duchenne muscular dystrophy.

Eteplirsen works by skipping exon 51 to overcome a genetic mutation to allow for the creation of dystrophin. This single solution is alledged to correct the body's inability to build muscle. The end point that Sarepta reported to the FDA was not however a detailed view of that mechanism of action. Rather they chose to remain in their mile high view and ask the FDA to look out the window while they spun their narrative. After a few more data points were added to the big picture, such as the failure of exon 51 skipping Prosensa in a larger study, the FDA decided they needed to see more rigor in Sareptas scientific method. Sarepta now has to add new endpoints, a longer study duration and a larger study population. Based on this new demand by the FDA to get more information, Sarepta lost $750M in market value this Tuesday.

The question I have for those who try and bring up the human side of the story and how this effects the patients is why are they bailing out? If the caring investment community and the leaders of Sarepta thought the 12 person trial was sufficient for a fast track approval by the FDA, why don't they think that the data offers some predictive powers over what would come from a more detailed study? The pot of gold still remains at the end of this journey. It's just gotten a little tougher. The Sarepta crew are one mile up in their airplane looking down at Venice Beach. The people in the watch tower have instructed them to take another pass and get a closer look at the beach before they move on. Are they afraid that they don't have a clue where the water really is?

The reason Sarepta is in business and has burned through well over $320M without putting a single drug on the market is due to the fact they are targeting RNA. The smoke and mirrors approach has them in trouble once again. They didn't spend that $320M studying Duchenne muscular dystrophy. They spent all of that money and still can't think of more convincing evidence for their product. What we on the outside know is that they are in business to make money. If they believe in their medicine they should forge ahead. The 12 patient sample size was enough for Sarepta to tell the FDA and the investment community that they are on to something that will help these boys suffering from DMD. The same fame and fortune awaits, it's just gonna be a little bit harder now. Now is the time when Sarepta has to stick to their guns and finish what they started. We've heard the narrative and we've heard about the results that has given people hope. We need to know more about this new exon skipping method, not just for DMD but for other single genetic mutation disorders. Either outcome, positive or negative, the patients and the scientific community have an interest in the scientific work of Sarepta.