No sooner was the human genome decoded than it was essentially forgotten by the biotech and pharma industries. Despite the enormous promise of knowledge that could, in theory, lead to the prevention and even cure of disease, the enormous technical challenges for developing, producing, targeting, delivering and activating these miracle treatments seemed too daunting and prohibitive. It didn’t help that one of the first patients to receive a treatment died. In 2000, the FDA concluded that the hyperbole has exceeded the results.
Thanks to a series of successes reported over the past five years against a variety of genetically-triggered conditions, notably against leukemia and severe combined immunodeficiency (SCID), gene therapy has emerged from what has been called the “lost decade” and is enjoying a modest renewal of interest.
From left, Frédéric Revah, Marina Cavazzana, Alexandra Glucksmann, and Clark Pan.
Frédéric Revah, CEO at Genethon, noted that this renewed enthusiasm for gene therapy is also driven by advances in genome editing technologies such as CRISPR/Cas-9 and Talen, and that large pharma and biotech are stepping cautiously forward into the space with investments and partnerships focused on both monogenic disorders and ultra-orphan indications.
At BIO-Europe Spring® in Paris, Revah moderated a panel discussion addressing key considerations along the product development pathway with the clinician Marina Cavazzana, MD, who leads the Department of Biotherapy at the Necker Children’s Hospital in Paris; Alexandra Glucksmann, Chief Operating Officer at Editas Medicine, and Clark Pan, Head of Discovery Therapeutics with Shire.
A 20-year veteran in the field, Glucksmann told participants during the session that originally she and her team were focused on gene hunting and that today their work with the CRISPR technology today is aimed at correcting those same genes that they had once hunted.
The excitement today, and the investments that the enthusiasm has encouraged, are owing to a simplification of the gene editing technology, she explained, and the advancement of clinical trials that suggest the treatments are less risky. Key to further success will be matching the techniques available with the needs, the ability to identify clear clinical endpoints for future trials and to have well-defined biomarkers.
“We have spent the last two years scanning the 9,000-plus genetic diseases trying to decide which ones we can tackle now,” she said, adding that Editas has mapped out its objectives and has set a strategy for the company.
Pan suggested that Shire’s focus on rare disease is a perfect fit for entering into the gene therapy space, and more specifically, it has sharpened the focus to areas of strength, such as central nervous system disorders and ophthalmology.
A first focus, he said, are monogenic disorders, which are more tractable, and then look to the appropriate technology.
“We are agnostic to the platform. Biology comes first, and technology is less of an issue,” he said.
The expertise, and moving gene therapy from preclinical work to the bedside, is really in the hands of academic partners, according to Cavazzana.
“Yet there is a lot of space that industry can occupy and where they can invest,” she suggested.
There are two steps in production, she said, and the first part of producing the virus is the easier one, with established techniques and technology that is advancing rapidly. The second step where cells are manufactured is a completely different kind of work that requires a specialized setup for each type of disease being addressed.
“At this point, I am not sure that industrial partners understand this,” she said. “It becomes a question of experience, and year after year we are making progress toward our goals. Scientifically, we are advancing in sickle cell anemia, HIV, and cancer. Manufacturing will be less and less of a problem because there is technology developing around the automatization of the processes. A key will be growing up the people in the secondary roles for following the patients and the cell effects.”
According to Glucksmann, all industry partners recognize that the transition from bench to the bedside needs to be seamless and will be based on an onsite expertise, which presents a challenge, but also an opportunity. The field is moving fast, and there needs to be a focus on standardizing this clinician-dependent production and delivery of the final product.
“It will take time, yes. Perhaps another 10 years. But success in the clinic will feed additional investment in the field,” she predicted.
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