Mallinckrodt has kicked off a phase II trial of its Duchenne muscular dystrophy candidate, a repurposed drug used for years for inflammatory and autoimmune diseases.
The first patient has been dosed with MNK-1411, a depot formulation of a synthetic melanocortin receptor agonist – also known as tetracosactide or cosyntropin – that mimics the activity of adrenocorticotropic hormone (ACTH) in the body. Current formulations of the drug is used to treat inflammatory bowel disease, rheumatoid arthritis and osteoarthritis in patients who can’t receive corticosteroid therapy.
Mallinckrodt has orphan drug status for MNK-1411 in the US and Europe as a treatment for DMD, and will have a period of market exclusivity for that indication if its new formulation succeeds in clinical testing and is approved, even though generics based on tetracosactide are available on the market.
DMD is caused by a lack of functional dystrophin protein, which assists in keeping muscles healthy. Patients with this progressive muscle condition have been known to lose the ability to walk as early as age 10, and can develop life-threatening lung and heart complications in their late teenage years and their early 20s.
While not affecting the underlying cause of the disease, it is hoped that MNK-1411 may delay the progression of DMD by stimulating cells through their melanocortin receptors to reduce inflammation and diminish muscle damage. It’s already completed a phase I trial to select dosing for the mid-stage testing.
While there is a lot of excitement about the potential of gene therapies to treat DMD, with encouraging early results from a Sarepta phase I/II trial, these could be some time off the market – particularly as Sarepta’s study has just been held up by a quality control issue.
For now, the only approved therapies are Sarepta’s exon-skipping therapy Exondys 51 (eteplirsen), which has some controversy over its efficacy, PTC’s Translarna (ataluren), which is available in Europe but was rejected in the US, and novel steroid Emflaza (deflazacort) from Marathon Pharma.
Mallinckrodt’s step forward comes shortly after another UK biotech, Summit Therapeutics, saw its shares go into freefall in June after its DMD candidate ezutromid failed a phase II trial. The Sarepta-partnered drug is an oral small-molecule modulator of utrophin, a protein that is structurally and functionally similar to dystrophin, and was being billed as a potential treatment for DMD regardless of the type of mutation affecting the dystrophin gene.
Other therapeutic approaches under test for DMD include gene-editing with CRISPR/Cas9, myostatin inhibitors from Pfizer, Bristol-Myers Squibb and Biogen/AliveGen, and Santhera’s antioxidant idebenone, which like MNK-1411 is designed to reduce the damage to muscles resulting from the genetic mutation.