World Muscle Society: Day 3 Highlights

Highlights from day three at the World Muscle Society meeting in Mendoza, Argentina, provided by CureDuchnne’s scientist, Dr. Mike Kelly. 

Mallinckrodt Pharmaceuticals

Mallinckrodt provided an update on their Phase 2 multicenter, double-blind, placebo-controlled study, assessing the safety and efficacy of MNK-1411 in Duchenne patients. MNK-1411 is an injectable synthetic 24-amino acid peptide analogue of adrenocorticotrophic hormone and an agonist of the melanocortin receptor. This novel mechanism of action is expected to delay the progression of Duchenne by reducing inflammation, in addition to helping diminish muscle damage.

Having completed an earlier Phase 1 clinical healthy volunteer trial in 2017, Mallinckrodt is now recruiting their Phase 2, multicenter, double-blind, placebo-controlled, multiple-dose study. The trial plans to enroll 132 boys with DMD, ages four to eight. (See NCT03400852 and attached study design.)

The primary outcome measure is a motor performance test involving a 10-meter walk/run at 24-weeks. Secondary outcomes will be other measures of motor performance and muscle strength, such as the NorthStar ambulatory assessment, four-stair climb test, rise from supine test and quantitative muscle testing using a dynamometer. The study is expected to be completed in April 2021.

Nationwide Children’s Gene Transfer

The team at Nationwide Children’s reported the latest results from an ongoing Phase 1/2 clinical trial with AAV-mediated gene transfer with GALGT2 in Duchenne.

The trial is an open-label, dose-escalation study to examine the intravascular limb infusion of the gene, delivered bilaterally via the femoral artery to the lower limbs. To accomplish this, the blood flow is interrupted in one leg via inflation of a venous and arterial balloon, and the vector dose is administered over 90 seconds while the blood flow remains interrupted for 10 minutes. Once the balloons are deflated and blood flow re-established, the procedure is repeated on the other leg. Two doses of the gene are planned: 2.5×10¹³ vg/kg/leg and 5×10¹³ vg/kg/leg.

The initial results for the first dose show that rAAVrh74.MCK.GALGT2 delivery is well tolerated without signs of local or systemic toxicity. Expression of GALGT2 was detectible, and the company presented initial results of efficacy (see below). The team is expecting to continue the clinical study at the higher dose level as well as conduct further non-clinical studies to support systemic administration to humans.

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