6 Biotech Powerhouses Making Progress In Duchenne Muscular Dystrophy
“Cooper Jones was no more than six and newly diagnosed with Duchenne Muscular Dystrophy, when punk rocker Jim Lindberg called him up on stage during a Pennywise show in Long Beach.”
Cooper Jones’s disability did not stop him from pursuing his passion. Imagine him performing on stage, standing on his own feet rather than performing with the help of a wheelchair. That would be such a confidence booster for him as a musician, right?
We all know that among all the muscular dystrophies, Duchenne Muscular Dystrophy (DMD) is one of the most severe forms of inherited muscular dystrophy. It is estimated that this disorder affects about one in 3,500 male births worldwide.
In the last few years, therapeutic options have advanced, with various drugs entering the market. Also, treatments such as gene therapies and myosin and HDAC inhibitors are still being considered and are at different stages of assessment. As the biotech industry progresses, let’s learn about the six biotech companies that are working towards making the lives of DMD patients better.
6 Biotech Powerhouses Making Progress In Duchenne Muscular Dystrophy
An RNA-focused company based in Cambridge, Massachusetts
, is rapidly advancing the research and development process to treat DMD. By building a new medicine platform called PRISM, the company designs therapies that repair, restore, or modulate proteins based on a specific target of disease, which is changing treatment modalities. The company recently got promising interim data from the phase trial evaluating WVE-N531 in boys with Duchenne muscular dystrophy. This is an exon-skipping oligonucleotide.A common form of mutation in the gene for dystrophin is exonic deletions, which can further disrupt the formation of the gene. In the case of Duchenne muscular dystrophy, loss of exon 52 prevents its juxtaposition with exon 53 on the same reading frame for the overall assembly of the gene. Such exon skipping therapy, such as WVE-N531, can remove the error-prone exon, in this case, exon 52, and restore the reading frame of mRNA and the dystrophin protein functionality.
Trial results reported that the mean absolute unadjusted dystrophin increase in patients after 24 weeks was at 5.5%. Wave also reported that mean absolute muscle content-adjusted dystrophin expression was at 9%. Most interestingly, in ambulatory participants, 89% achieved muscle content-adjusted dystrophin levels of at least 5% with a mean exon skipping rate of 57%, as determined by RT-PCR.
This was after the FDA had designated the drug candidate a Rare Pediatric Disease. The company also raised $200 million in a public offering during the month of September.
Another Cambridge, Massachusetts-based company, Sarepta Therapeutics, is one of the biggest and most famous names in DMD. One of its gene therapies, ‘Elevidys’ was approved last year for use in patients aged from 4-5. In June, the approval of Elevidys was expanded to all patients four and above.
Elevidys works by introducing a gene encoding a truncated form of the dystrophin protein into the muscles of patients suffering from mutations in the dystrophin gene.
Still, though, Elevidys is not Sarepta’s first success, having received controversial FDA approval for another DMD drug, ‘Exondys 51’.The company also is in clinical development of its RNA-targeted therapy, SRP-5051 (vesleteplirsen). Vesleteplirsen is a drug candidate created to bind to exon 51 of dystrophin pre-mRNA for the purpose of facilitating exon skipping, an applicable approach in approximately 13% of children with DMD who have mutations matching this exon skipping approach.
The only publication so far for the latest Phase 2 clinical trials data of SRP-5051 came out this year with some promise. The candidates showed a mean expression level for dystrophin at 5.17% and a mean exon skipping rate at 11.11% at week 28. However, serious adverse events occurred in 7; hypomagnesemia affected 4, and hypokalemia affected 3.
6 Biotech Powerhouses Making Progress In Duchenne Muscular Dystrophy
California-based company ‘Capricor’ is conducting phase 3 testing on its drug, ‘Deramiocel’, and plans to submit a Biologics License Application(BLA) to the FDA for full licensure. Cardiomyopathy is the leading cause of death for DMD patients. Its a group of diseases that involve the heart muscle. Once “Deramiocel” is approved it will be the first drug directed at treating cardiomyopathy in DMD.
Deramiocel is created from cardiosphere-derived cells(CDC), a native population of stromal cells derived from healthy human heart tissue. CDCs possess immunomodulatory, anti-inflammatory, pro-angiogenic, and anti-fibrotic features, which are attained by exosomes carrying bioactive materials.
The studies have demonstrated the drug to be useful and to possibly slow up the course of the disease in patients who have late-stage DMD. Capricor has licensed the U.S. rights for the drug to “Nippon Shinyaku,” a major Japanese multinational company, and has sold the rights for commercialization in Europe for $35 million.
Edgewise Therapeutics is a company based in Colorado that’s working to address muscle dystrophies, with an initial focus on Duchenne and Becker muscular dystrophies. The two are genetic but cause different forms of progressive weaknesses in muscles. Whereas DMD progresses more severely and quickly than Becker muscular dystrophy. Essentially, the skeletal myosin inhibitor developed by the company, “sevasemten,” protects fragile muscle tissue from the damage caused by contractions in muscular dystrophy patients. The treatment is now under phase 2 in the clinical trials.
It will be presented at the 29th International Annual Congress of World Muscle Society in Prague, Czech Republic, next week. This particular drug received Fast Track status from the FDA earlier this year in treating DMD. In January, the company raised $240 million in an offering.
Italfarmaco is an Italian biotech firm specializing in developing zinc-dependent histone deacetylase (HDAC) inhibitors. HDACs are key regulators of gene expression and have been widely studied as potential anticancer drugs. They also have promising results in the treatment of muscular dystrophies, including DMD.
“Givinostat”, known today under the brand name “Duvyzat,” has been recently approved by the FDA for the age group 6 years and above. It is an important milestone because it is actually the first nonsteroidal drug to be ever authorized in the United States for people carrying any genetic variant of DMD.
Duvyzat works by blocking the enzymes histone deacetylases, which are mechanisms within cells that control gene expression. By inhibiting such an enzyme, it induces muscle repair, rejuvenates the fibers, prevents or at least reduces inflammation, and decreases fibrosis.
It relied on a phase 3 clinical trial with 179 boys diagnosed with DMD for its approval of the drug. The objective of the trial was met with a “statistically significant and clinically meaningful difference in time to complete the four-stair climb test.” The four-stair climb test is an assessment of the strength of leg muscles and one’s capacity to move the muscles along with one’s cardiovascular ability; a participant runs as fast as he can up four stairs.
This drug is hoped to be applied in future clinical practices as an adjunctive drug in patients with DMD. Further, Italfarmaco’s research is focused on other diseases of the neuromuscular apparatus, disorders related to fibrosis, and malignancy.
California-based biotechnology company Avidity Biosciences is developing several therapies to treat muscle disorders. One of the company’s lead candidates, “delpacibart zotadirsen”, which has recently concluded a phase 1/2 clinical trial targeting DMD.
The system is designed to target phosphorodiamidate morpholino oligomers (PMOs) directly into skeletal muscle and cardiac tissue for the skipping of exon 44 of the dystrophin gene. PMOs are synthetic drugs that can alter gene expression to increase the production of dystrophin.
During the trial, dystrophin levels in patients got increased by 25%, and creatine kinase levels got reduced to nearly normal ranges. Creatine kinase is an enzyme very important for energy production in cells; it is mainly found in the heart, skeletal muscles, and brain. High amounts of this enzyme are related to the early symptoms in DMD patients, even in newborn patients with such affections.
The experimental drug caused a 37% elevation in exon 44 skipping, which reached as high as 66% skipping at a dose of 5 mg/kg after four months of therapy. The investigational drug del-zota has received Orphan designation from the FDA and the EMA, as well as Rare Pediatric and Fast Track designations by the FDA.
6 Biotech Powerhouses Making Progress In Duchenne Muscular Dystrophy
Talking about the worldwide therapeutic landscape for DMD
The global DMD drugs market was estimated at $3.2 billion in 2023 and is expected to reach $8.6 billion by the end of 2032. This rising growth is majorly by the approval of drugs such as Nippon’s exon skipper Viltepso, Sarepta’s Elevidys, Exondys 51, and Amondys 45, PTC Therapeutics’ corticosteroid Emflaza, and Italfarmaco’s Duvyzat, among others.
There are also several other candidates in the competitive landscape, such as Myosana’s early-stage gene therapy from the United States, Satellos Bioscience’s stem cell strategy from Canada, and Dyne Therapeutics’ preclinical exon-skipping therapies based in Massachusetts. The Parent Project Muscular Dystrophy has also publicly voiced support for Myosana’s gene therapy platform, committing $500,000 to help advance its treatment for DMD.
In this race to win over Duchenne muscular dystrophy, six biotech powerhouses with innovative therapies are at the front of the participants. From gene treatments to innovative drug designs, their tireless pursuit of cure brings hope to patients and reshapes the future of DMD care.
6 Biotech Powerhouses Making Progress In Duchenne Muscular Dystrophy
