Wave Life Sciences prepares next gen Duchenne drug for trials

Small biotech firm Wave Life Sciences says it has a 'next generation' pipeline for Duchenne Muscular Dystrophy (DMD) which could prove far more potent than the treatments currently struggling to gain FDA approval.

BioMarin's drisapersen was rejected by the FDA in January, and Sarepta's eteplirsen was also given the thumbs down by an FDA advisory committee on 25 April.

Both are exon-skipping drugs, which "skip over" the mutated exon, enabling the gene to once again code for and produce functional dystrophin, the muscle building protein which is missing in Duchenne patients.

The drugs have been repeatedly rejected by regulators for failing to show sufficient proof of efficacy.

Sarepta's drug may still reach the market, thanks in part to the desperation of parents of boys with the condition, but there is no doubt a more effective treatment is needed.

Yesterday Cambridge, Massachusetts-based Wave said pre-clinical data on its next generation exon-skipping molecules have shown around a 25-fold improvement in exon-skipping efficiency compared to drisapersen and eteplirsen,

It says its drugs could be more potent and have an enhanced ability to restore the production of functional dystrophin. In addition, it says its proprietary muscle targeting technology has shown substantial improvement in distribution to critical tissues in animal models, including skeletal muscle, diaphragm, and heart.

"We recognise the acute need of the Duchenne community for therapeutic options to address this devastating disease, and also appreciate regulators' requirements for strong, well-validated, scientific evidence. Our goal is to fulfil both of these needs by bringing forward optimally designed drugs through robust clinical trials," said Paul Bolno, president and chief executive of WAVE Life Sciences.

"Based on the strong preclinical data we've seen to date, we are highly encouraged that we are on track to develop exon-skipping medicines that maximise potency with a favourable safety profile."

Sarepta has been criticised for not following up on FDA advice to make their trials more robust, a mistake Wave and others in the field aim to capitalise on.

"We plan to conduct rigorous, well-designed clinical trials that explore various predictive biomarkers and evaluate comprehensive endpoints," added Bolno.

Wave's initial DMD candidate skips exon 51 in the dystrophin gene. The company will initiate IND-enabling studies in 2016 and plans to start its first clinical trial of the candidate in the second half of 2017. WAVE will also use its novel stereopure chemistry platform to advance therapies targeting additional DMD-related exons to expand the potential impact of its approach to a broader group of patients.

Wave has an ongoing research collaboration with the University of Oxford to advance stereopure nucleic acid therapies for DMD across exons. Oxford's Matthew Wood, M.D., Ph.D., Professor of Neuroscience, Department of Physiology, Anatomy and Genetics, Medicine Sciences Division, and his team will continue to work with the company to use its company's proprietary platform to enhance oligonucleotide approaches, including exon-skipping, to address the rare genetic muscle disease.

The firm has also just announced a deal with Pfizer for the development and commercialisation of nucleic acid therapies aimed at silencing the underlying causes of debilitating metabolic diseases. The collaboration will focus on genetically defined targets and bring together Wave’s stereopure drug development platform, across antisense and RNAi modalities, along with GalNAc and Pfizer’s hepatic targeting technology for enhanced delivery to the liver.

The company had a successful initial public offering (IPO) last November, despite the flotation coinciding with a major downturn in biotech stocks, and last year raised its R&D spending to $9.1 million.