“We made important achievements in 2022 but we still face key challenges in the year ahead”
Frédéric Revah, CEO of Genethon looks back on the year 2022 marked by major advances for gene therapy and presents the challenges ahead in 2023
“ In 2022, Genethon has achieved three major milestones in the clinical trials that we are sponsoring. First of all, our gene therapy trial for Duchenne muscular dystrophy resumed, following an exceptional partnership between sponsors of several gene therapy trials currently in progress for this disease. This partnership helped us understand the origin of the unwanted side effects observed both in our trial and in others. Since then, additional boys have been treated, and the trial continues to recruit. A first patient was treated in a European gene therapy trial for FKRP-related limb girdle muscular dystrophy. This signaled the culmination of 30 years of high-level research conducted in our laboratory by the team of Isabelle Richard, a world specialist in these pathologies. This trial is led by Atamyo Therapeutics, a spin-off of Genethon, which we created to speed up gene therapy development for limb girdle muscular dystrophies. We also aim to bring four other products for four other types of limb girdle muscular dystrophy to the clinical stage. An exceptional pipeline.
Lastly, the entry into pivotal phase of the trial for Crigler-Najjar syndrome is the result of the positive data obtained in the initial clinical trial among the first patients treated. We are delighted with this new step, which brings so much hope to patients affected by this serious liver disease.
A total of 13 of our gene therapy products stemming from our R&D have reached clinical trial throughout the world and 6 others should reach this phase in the coming three years.
Challenges ahead
Gene therapy has reached maturity, shows a strong dynamism, and the wide variety of trials and medications currently available – 24 in total for rare genetic diseases as well as for several forms of cancer – demonstrate that this innovative technology, which we have helped to develop, has become a distinct form of medicine.
Five new gene therapy products were approved in 2022 in the US or in Europe: Biomarin’s Roctavian for Hemophilia A; UniQure’s Hemgenix for Hemophilia B; PTC’s Upstaza for AADC deficiency; Ferring’s Adstiladrin for NMI Bladder Cancer; and Janssen’s Carvytki CAR-T approach. 2023 could be even more productive with 11 new products being considered for registration, half of which for genetic diseases. However the field, and by extension Genethon, face several crucial challenges in 2023.
The first concerns patients’ access to these innovative medications, particularly in the field of rare diseases. The 7,000 known diseases affect 350 million people throughout the world, but individually they affect sometimes only a few hundred patients. Although very many rare diseases could benefit from gene therapy treatment based on the treatment paradigm developed over the past few years, the rarity of some of these diseases and the high cost of both product development and production mean that pharma and biotech companies don’t consider them “profitable” enough. It is therefore vital to find a creative economic model and also to innovate in terms of bioproduction to reduce costs, control the price of medications sold and as a result secure access. To help meet this challenge, in addition to the daily efforts of its experts on these issues, Genethon has joined the Bespoke Gene Therapy Consortium, launched in October 2021 by the Foundation for the National Institutes of Health.
The second challenge involves immune response control. This immune response, in particular for AAV vectors, is a limitation on re-dosing of the product, which may be necessary for a patient already treated. Some patients (up to 30-40%) also have natural immunity against the vectors and are not eligible for treatments. Lastly, in some cases, the immune response to injected products may be the cause of side effects.
We need to design innovative strategies to control and bypass these immune responses. Genethon is working on this, with promising research taking place in one of our teams to overcome this hurdle. We hope to be at the forefront of innovation for this second generation of gene therapies as we were for the first generation at the end of the 1990s.”
