Vertex’s second transformation: Duchenne time

The cystic fibrosis player does deals with Crispr and Exonics to launch itself into a highly competitive rare disease area.

Vertex is no stranger to makeovers, having already switched from hepatitis C to become a highly successful cystic fibrosis player. Yesterday it sowed the seeds for what could become its second transformation – into a company specialising in treatments for Duchenne muscular dystrophy.

Its basis for building a pipeline here is two deals that together cost the company $420m. The fact that there are at present still just two not particularly effective DMD treatments on the US market illustrates the opportunity, but unlike in cystic fibrosis Vertex will have to pedal hard to catch up with the DMD leaders.

This is because since the controversial approval of the first treatment, Sarepta’s Exondys 51, the industry pipeline for DMD has mushroomed. Indeed, EvaluatePharma reveals over 30 projects in phase II-III clinical trials alone.

Selected Duchenne muscular dystrophy projects
Project Company Mechanism 2024e sales ($m)
Golodirsen Sarepta Therapeutics Exon 53 binding oligonucleotide RNAi 331
Phase III
Casimersen Sarepta Therapeutics Exon 45 binding oligonucleotide 250
Suvodirsen Wave Life Sciences Exon 51 binding oligonucleotide 235
Edasalonexent Catabasis Pharmaceuticals NF-kB inhibitor 227
RG6206 Roche/Bristol-Myers Squibb Myostatin (GDF8) inhibitor -
Givinostat Italfarmaco HDAC inhibitor -
Phase II
SRP-9001 Sarepta Therapeutics Microdystrophin gene therapy 1,820
SGT-001 Solid Biosciences Microdystrophin gene therapy 577
Pamrevlumab Fibrogen Connective tissue growth factor MAb 381
Vamorolone Santhera/Idorsia NF-kB inhibitor 293
NS-065 Nippon Shinyaku Exon 53 binding oligonucleotide RNAi 218
PB1046 Phasebio Pharmaceuticals VIP2 agonist 87
GALGT2 Sarepta Therapeutics GALGT2 gene therapy 3
ATL1102 Antisense Therapeutics/Ionis Alpha-4 integrin antisense -
TXA127 Constant Therapeutics GPCR peptide agonist -
AAV1-Follistatin Milo Biotechnology Myostatin (GDF8) inhibitor -
MNK-1411 Mallinckrodt Melanocortin-2 receptor agonist -
Phase I
PF-06939926 Pfizer (ex Bamboo) Microdystrophin gene therapy -

Vertex’s bid to compete will come courtesy of a $175m technology licence from Crispr Therapeutics, with which it already collaborates on sickle cell disease and beta-thalassaemia, and the $245m acquisition of the private gene editing business Exonics Therapeutics.

Together, these two tie-ups will give Vertex the scientific tools to work on new treatments for DMD and myotonic dystrophy type 1. These tools comprise Crispr’s Crispr/Cas9 technology, endonucleases, single and double-cut RNAs and AAV vectors, and the single-cut Crispr tech Exonics licensed from UT Southwestern Medical Center.

Vertex’s most important competitors will be Sarepta, Solid Biosciences, Pfizer and Wave Life Sciences, but numerous others are waiting in the wings too. This is quite the turnaround from just a few years ago, as the life sciences investor Brad Loncar pointed out yesterday.

Having launched Exondys 51 Sarepta is now awaiting US approval of its second exon-skipper, golodirsen, in the gene therapy space that Vertex is entering. Sarepta’s biggest immediate hope is the microdystrophin project SRP-9001, while the first data from Pfizer’s PF-06939926, acquired with Bamboo Therapeutics for $150m, are due later this month.

Vertex said that along with DMD it would be seeking to develop treatments for myotonic dystrophy type 1, another muscle function disorder that has a different genetic cause. The competitor pipeline here is much thinner, with clinical projects comprising AMO Pharma’s AMO-02 and Ionis’s baliforsen, and Avidity Biosciences, Expansion Therapeutics and Audentes working on preclinical assets.

Evercore ISI analysts yesterday wrote that myotonic dystrophy type 1 might represent a larger prevalent population than DMD. If this is the case, and considering the competitor landscape, perhaps the former disease has the greatest potential for Vertex to make its mark.

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