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|
|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||-|
|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 Pharmaceuticals||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||-|
|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, meanwhile, 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.