Professor Annemieke Aartsma-Rus shares her highlights of the PPMD Conference 2022 that was taking place June 23-26 in Phoenix Arizona. This overview contains highlights regarding late breaking news on trial results, gene therapy, and exon skipping.
The talks were great but also really good to meet patients & parents, hear their stories & explain the basics. You are not letting your child down if you don’t fully understand genetic & scientific aspects. You need to understand risks and potential benefits to make decisions.
Late Breaking Talks on trial results
- The givinostat phase 3 trial from Italfarmaco met its primary endpoint (significant effect in 4 stair climb) and treatment group did better on all secondary endpoints after 72 weeks.
- The ataluren phase 3 trial from PTC Bio showed a significant difference on 6 minute walk test after 72 weeks treatment. Also here secondary endpoints were better for treated group.
- 1 year open label extension follow up data from the HOPE-2 trial Capricor were presented.
This is a waiting game as running trials take time. Notably, combination therapy of dystrophin restoration and improving pathology is considered and for certain trials patients who are treated with exon skipping drugs can participle.
Inclusion criteria on gene therapy trials
For gene therapy trials inclusion criteria have changed. This is because it has become apparent that the N-terminal part of the microdystrophin triggers an anti-dystrophin immune response in patients with large deletions at the start of the gene.
- Pfizer now excludes patients with deletions involving exon 9-13 or 29-30;
- Sarepta excludes deletions involving exon 1-17 & exon 45 deletions.
- Solid probably will exclude patients with deletions involving exon 8-13 & 42-45 (nNOS binding site: only present in their microdystrophin)
Overview on exon skipping trials
For exon skipping there is a lot happening for different exons. An overview per exon:
Exon 45: casimersen (PMO from Sarepta) is FDA approved.
Exon 53 viltolarsen (NS Pharma) and golodirsen (Sarepta) are FDA approved and Wave has an ongoing trial with a stereopure ASO.
Exon 44: avidity is preparing a trial with a transferrin-antibody conjugated ASO to improve muscle uptake; entrada is preparing a trial with an arginine rich cyclic peptide to improve delivery and endosomal escape.
Exon 51: eteplirsen is FDA approved (Sarepta). Trials with high dose eteplirsen & Vesleteplirsen (arginine rich peptide) are ongoing (both Sarepta). Dyne is preparing a trial with a transferrin-antibody conjugated ASO. Pepgen is preparing a trial with an arginine rich peptide and Biomarin is preparing a trial with a chemically modified ASO.
Exon 2 duplications: Kevin Flanigan runs a clinical trial for exon 2 duplications with an antisense gene (U7 snRNA). For older patients dystrophin restoration was relatively low (1% and 6%), while for a baby treated at 5 months, dystrophin levels were 70%.
A lot is happening – phase 2 & 3 trials take time to generate results, but now that multiple trials are ongoing for different approaches, results will keep coming in steadily the next years. Hopefully more positive results will come!
Photo courtesy of PPMD USA