Author: Jean-Claude Muller, 穆卓Executive Editor at BtoBioInnovation  jcm9144@gmail.com

SPECIAL REPORT #2

Cell and Gene Therapy: The next wave of innovation?

With three gene therapy products already on the market and the approval of the first chimeric antigen receptor (CAR) T cell treatments, Kymriah (tisagenlecleucel) and Yescarta (axibactagene, ciloleucel) in 2017, gene replacement therapies and cell therapies are no longer considered as “exceptional” in the arsenal of pharma companies.

A series of recent events tend to confirm that these new therapies will be part of the new wave of innovation in the years to come.

On January 15, Dr. Scott Gottlieb, commissioner of the US Food and Drug Administration, announced that the FDA will be drafting new guidance for gene replacement therapies as well as cell-based therapies. “Gene therapies products now have the potential to cure intractable diseases and fundamentally alter the trajectory of many other vexing illnesses. To advance these opportunities the FDA plans to introduce new policy guidance and other advances in our drug development framework in 2019” Dr. Gottlieb said. Meanwhile clinical trials of cell therapies and gene therapies are increasing at a fast pace.  In his announcement Dr. Gottlieb disclosed that the FDA currently has more than 800 cell and gene therapy Investigational New Drug (IND) applications to review. He compared the wave of new cell and gene therapies to the coming of age of antibodies in the late 1990’s. The FDA expects to receive more than 200 IND’s for these drugs by 2020 and it could be approving as many as 10 to 20 cell and gene therapy drugs by 2025, based on the current existing pipeline and clinical success rates of these products.

It comes therefore as no surprise that the number of business deals in this area is also growing rapidly.

Novartis, has announced, in early November, at its annual R&D update, that it aims at establishing leading position at cell-based therapies and gene replacement therapies. To secure its position it has recently acquired AveXis (Chicago, USA), a gene therapy company as well as CellforCure, a contract manufacturer, belonging to the LFB Group (Paris, France) to access its cell and gene manufacturing facility located in Les Ulis (France).

Several other deals on this topic have been disclosed in recent months.  Sanofi which invests in BioNTech (Mainz, Germany) to access messenger RNA technologies and manufacturing capacity.  Bluebird bio (Cambridge, USA) acquiring rights from Inhibrx (La Jolla, USA) to expand its pipeline of CAR T cell therapies and collaborating with Regeneron to design T cell therapies targeting extracellular and intracellular tumor antigens.  Sensorion (Montpellier, France) has signed a letter of intent with the Pasteur Institute (Paris, France) to use gene therapies to correct monogenic forms of hereditary hearing loss, including Usher Syndrome type 1 and otoferlin-deficiency. Sirion Biotech (Munich, Germany), which specializes in viral vector technologies for gene and cell therapies, collaborates with Denali Therapeutics (South San Francisco, USA), which works on technologies to deliver therapeutic agents to the brain, to generate new gene therapies to treat neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease as well as amyotrophic lateral sclerosis (also called Charcot’s or Lou Gehrig’s disease).

China, which has been known as a silent but fast adaptor of new technologies, with sometimes poor respect of international guidelines, has created a major uproar when a Chinese scientist reported, in a November 2018 YouTube video, use of Crispr gene editing technology to alter the CCR5 gene in two embryos, after twin girls bearing the DNA changes were born.  “It is profoundly unfortunate that the first apparent application of this powerful Crispr technique to the human germline has been carried out so irresponsibly” said Dr. Francis Collins, director of the US National Institutes of Health.

The manufacturing logistics of transporting cell and gene therapies is far of being trivial and needs to reach the appropriate scale in order to become successful. Manufacturers will have to meet very specific needs, far beyond the traditional cold-chain model, to guarantee shipment integrity and delivery deadlines on a global scale.

Once this hurdle is being passed smoothly, it should not be too long before we see if gene replacement therapies as well as cell-based therapy products will contribute as a major innovation driver of the pharma industry. Next generation CAR T therapies from Celgene, Cellectis, Celyad, Gilead and Novartis are already being developed to become highly attractive solutions for patients in the future. The adoption of the linked new platforms will progressively become visible as more and more traditional R&D activities will be cut back in many pharmaceutical companies while new startup companies will rapidly emerge.

This document has been prepared by btobioinnovation and is provided to you for information purposes only.  The information contained in this document has been obtained from sources that btobioinnovation believes are reliable but btobioinnovation does not warrant that it is accurate or complete. The views presented in this document are those of btobioinnovation’s editor at the time of writing and are subject to change.  btobioinnovation has no obligation to update its opinions or the information in this document.