Sanoosa Blogs

Sarepta’s Duchenne Drug, the FDA & the Sorry State of Medicine Development


Wolfgang Kissel and Herbert Treutlein, 9 May 2016

Last week, biotech company Sarepta experienced a large setback when a majority of an FDA expert panel recommended not to approve Sarepta’s drug eteplirsen for the treatment of Duchenne muscular dystrophy DMD.  

Duchenne muscular dystrophy is a rare fatal disease affecting boys with an average life expectancy of 25 years. DMD is caused by a mutation on the X chromosome.  No cure exists currently for this quite debilitating disease.  

Sarepta has run a small clinical trial with 12 patients and some comparisons.  7 out of 13 experts rejected the data as ambiguous and not conclusive that the drug would work.  There were no safety concerns, just a question whether the drug mechanism of action is working or not.  DMD patient groups, however, gave evidence that the drug was working with their boys and worth trying out. 

“Although the FDA is prepared to be flexible with respect to a devastating illness with no treatment options, flexibility does not mean approving drugs for which substantial evidence of effectiveness has not been established,” reviewers from the FDA wrote in a briefing document ( 

So, this case made the headlines and Sarepta’s shares went on a roller-coaster. What did not make the headlines was a Nature News article in 2015, which stated that the ten highest grossing drugs in the USA work only for 4-25% of patients (Schork, N. J. (2015). Personalized medicine: Time for one-person trials. Nature News, 520(7549), 609–611. ). 

What does this mean for our health-care system? Let’s have a closer look. Chrestor, a drug for treating high cholesterol, works, according to the Nature News article, only in 5% of patients, meaning for 95% of patients the drug is either subpar or not working. In 2015 the revenue for Chrestor was $5.017 Billion, meaning that $4.766 Billion were just wasted. And this is just one drug of the top 10 drugs.

Let us have a look at one of the statistically better ones, Humira, a drug treating Athritis, works only in 25% of patients. With a worldwide revenue of $14.012 Billion in 2015 one could say that a staggering $10.509 Billion are wasted and without improving health for 75% of patients.

Have a look at the article and work out for yourself the immense burden on health-care systems imprecision medicine creates. 

In addition, that “not working” drugs have no efficacy, many drugs have severe side effects and adverse effects from medicines and medical treatments are the 3rd largest cause of death in the US. For death from negative drug effects this translates in the US into ca. 100,000 per year (

So, what has this to do with Sarepta’s case? Well, it is about this question what the outcome is of the Billion dollars of investment in medicine development, which at the end is covered by all of us.

Should a drug which is safe and which might work for a non-curable disease for some patients and not for other patients be approved even when the clinical trials might not have been to the highest standards? Shouldn’t we be ensured that the drug is working for the fast majority of patients? As mentioned above “…the FDA … does not mean approving drugs for which substantial evidence of effectiveness has not been established”.

So, it is about substantial evidence of effectiveness. Applying this approach to the highest grossing drugs and the results shown in Nature News, wouldn’t that mean: Do the FDA and the big pharma companies ever know for sure how a drug works in a complicated and complex biological organism like a human? In the last decades our understanding of biology has changed dramatically and there is no reason to believe that in 2016 we now know everything there is to know. 

If the FDA and similar organizations in other countries would only approve drugs they know how they work, then why are the ten most selling drugs effective in only 4-25% of patients?  

Wouldn’t it be time to require large clinical trials just to test safety and publish tests on the effectiveness so that patients and doctors can make up their minds whether to try medicine/therapy or not?  Wouldn’t it be time to approve personalized medicines to aid precision medicine to come about which require single-person-clinical-trials? How many drugs that could be potentially lifesaving for certain patient groups have been thrown out because some experts did not think the results were unambiguous?

This new thinking was well expressed by David Bohm who said, “I think people get it upside down when they say the unambiguous is the reality and the ambiguous is merely uncertainty about what is really unambiguous. Let's turn it around the other way: the ambiguous is the reality and the unambiguous is merely a special case of it, where we finally manage to pin down some very special aspect. “

We believe that it is time for an approach to develop medicines with a philosophy of precision and not with the trial and error approach still in place. The technologies are already there and are further emerging. We at Sanoosa, e.g. have developed and apply computational methods to accelerate and improve drug discovery to make better medicines. Other start-ups work on a similar mission. If only 10% of the money wasted for non-working drugs would be invested in such evolving technologies, we might prepare for a quantum leap in R&D productivity. Wouldn’t that be nice?

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