Earlier this week, the scientist in me was shocked by the ~$700M
acquisition of Prosensa by orphan disease company BioMarin for its Duchenne Muscular Dystrophy splice modulation candidate drisapersen.
My initial surprise was due to drisapersen being a drug that had not long ago gloriously failed a pivotal phase III trial, not least due to a questionable therapeutic index. All this is not very surprising since drisapersen is based on antiquated oligonucleotide chemistry (2’-O-methyl phosphorothioate).
After a moment of reflection though, I have come to take a more positive view of the deal as it is actually a very bullish sign of the interest by the
wider pharmaceutical industry in RNA Therapeutics. This is because BioMarin is taking the gamble here that it will be able to argue its way to approval by
pointing towards drisapersen having shown evidence that it can positively influence the splicing of
the disease-causing gene, dystrophin. So
even if your clinical evidence of efficacy is anecdotal at best, it is
difficult to argue with the notion that such evidence in combination with being
able to positively impact the root cause of a disease is not an important
step in treating an orphan disease of very high unmet medical need.
It should be clear to everybody that if drisapersen can get marketing approval, other exon 51 splice skippers with superior chemistries
(many of which are pushing forward in development) will eventually replace it as
best-in-class. I would be surprised if BioMarin
did not see it the same way, but similar to Roche acquiring Intermune for $8.3B for its IPF
drug which had marginal efficacy in a severe disease of high unmet need, the rationale seems to be that being first-to-market in such pioneer indications will allow you to
build a strong franchises in those areas.
It will be interesting to see whether this strategy pans out and
BioMarin can
get accelerated approval in 2015-6 based on some seemingly positive phase IIresults in combination with the dystrophin biomarker evidence.
Regardless, the $700M valuation and ~60% premium of the offer to its
stock price is a powerful reminder that part of the reason what makes RNA
Therapeutics so compelling is that it often allows you to drill down to the root cause of a disease. From a commercial perspective this is particularly valuable in an environment favoring drugs for severe orphan
diseases.
3 comments:
Precise Correction of the Dystrophin Gene in Duchenne Muscular Dystrophy Patient Induced Pluripotent Stem Cells by TALEN and CRISPR-Cas9
In this study, as a proof-of-concept of such gene therapy for DMD, we performed and demonstrated genetic correction of the dystrophin gene in patient-derived iPSCs by using three different methods: (1) disruption of the splicing acceptor to skip exon 45, (2) introduction of small indels to modulate the protein reading frame, and (3) knockin of the missing exon 44 to restore the full protein coding region. We then performed comprehensive genome-wide mutation analyses to assess the risk of off-target mutagenesis in 14 iPSC clones treated according to the TALEN or CRISPR approach. Our results demonstrate that genetic correction by these approaches in patient-derived iPSCs considerably lowers the risk of off-target mutagenesis and thus holds promise for DMD gene therapy.
http://www.cell.com/stem-cell-reports/fulltext/S2213-6711%2814%2900335-X
Failing to Rise to the Challenge What the FDA should learn from Ebola. Dec 1, 2014, Vol. 20, No. 12
A recent example of the FDA’s indefensible inconsistencies is its October decision to demand more data yet again—without clear, science-based standards—for companies seeking approval for several new drugs that should be available now to patients with the fatal disease of Duchenne muscular dystrophy.
What makes the muscular dystrophy pronouncements worse is that there are signs that they are driven by the FDA’s worst cultural tendencies: retaliation behind closed doors, “leveling the playing field” for competing companies by slowing down the company in the lead, and improperly relying on outside advisers with a strong financial interest in the outcome of its decisions.
As the new Congress establishes its oversight priorities, this shameful mess should be high on its list.
The FDA should learn from its mistakes. It needs to be more proactive with guidance on the standards for approval of drugs for Ebola and other tropical diseases, more transparent about the safety and efficacy of investigational drugs for Ebola, and more understanding about why randomized trials for rare diseases are often not feasible. When it comes to children dying of muscular dystrophy, the FDA needs to show more of the urgency it displayed when approving investigational Ebola drugs for heroic public health workers.
Michael Astrue is a former commissioner of Social Security and a former HHS general counsel.
http://www.weeklystandard.com/articles/failing-ris-challenge_819713.html?page=2
Imagine how wealthy the founders of Voyager will be when they receive an offer like that. Dirk and Kay will be chuffed.
Especially when they didn't even have to take a licence from their nemesis, BLT.
Though there is a small chance that it could end up being Avocell MkII.
Where is PFE?
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