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Gene Therapy Can Take Us Far If We Seize Its Long-Term Possibilities

Former President & CEO

Geoff MacKay | Former President & CEO

Last month marked another historic moment for gene therapy. For the first time in five years, the U.S. Food and Drug Administration’s Cellular, Tissue and Gene Therapies Advisory Committee met to consider a new product application. Two, in fact. With a pair of gene therapies to review from the Cambridge, MA company bluebird bio, the committee voted unanimously in favor of both.

The clinical data presented, and the testimonials of patients, caregivers, physicians, and the sponsor, all emphasized the transformative potential that hematopoietic stem cell (HSC) gene therapy using lentiviral vectors can have for patients living with serious conditions. For those of us working to develop new gene therapies, these testimonials are always a humbling reminder of the importance of the work taking place across the industry. Additionally, the committee made no requests for longer efficacy follow-up data. I believe these recent developments further support the value of HSC gene therapy using lentiviral vectors, especially in rare diseases with CNS manifestations and for diseases where early treatment is needed.

But at the same time, the hearing may signal a long-term challenge. If we do not accelerate the development of gene therapy and expand our disease focus beyond ultra-rare diseases, we could miss a valuable opportunity to deploy this technology against other diseases that cause significant disability and mortality in our society.

The recommendations made by the advisory committee demonstrate the valuable progress that has been made in cerebral adrenoleukodystrophy (CALD) and beta thalassemia, both life-shortening and life-limiting conditions. As an industry we need positive milestones like the advisory committee’s unanimous recommendations to continue to build our scientific knowledge and to secure the capital resources to keep moving forward, and we are beholden to the patients, clinicians, sponsors, and investors who make that possible. But throughout the committee’s discussions, I heard several themes that underscore gene therapy’s long-term potential to address more common genetic diseases:

  • No new safety signals of broad significance – The safety issues discussed last week have not been observed in the hundreds of people who have been treated to date with other gene therapies using lentiviral vectors. The committee appeared to be constructive in their approach to assessing HSC gene therapy and evaluated each gene therapy based on its own unique risk-benefit analysis. Their post marketing surveillance (PMS) requests were pragmatic and reasonable. Risk is inevitable in the treatment of any serious genetic disease, even in the current standard of care, but those surrounding gene therapy are much better understood and characterized now than in the past. Importantly, the emerging clinical data from HSC gene therapy trials have made the risks more predictable and thus potentially more manageable.
  • Not all lentiviral vectors are designed the same – Vectors have a starring role in gene therapy, as they deliver the required therapeutic gene to modify the cell’s genome. But the hearing repeatedly highlighted the differences between vectors and how they are each designed to specifically target the type of disorder being treated. Just as there are different types of adeno-associated viral (AAV) vectors – mostly designed to extend reach in particular tissues – there are also distinct differences between the lentiviral vectors used in HSC gene therapy that calibrate their properties in different contexts. Different companies use different versions of the lentiviral vector, different promoters, different transgenes and different manufacturing processes based on the disease they are targeting. This flexibility and adaptability offers possibilities that we have only just begun to explore.
  • Ability to treat babies and young children with head-to-toe reach – We heard several times during the testimony that “Time = Brain,” when discussing the urgency to treat CALD. That statement gets at the root of our belief in how important it is that we develop gene therapies that can be dosed early in a child’s life, before their disease causes irreversible damage, and that can reach the entire body, including the brain. Both the ability to treat early and reach the brain are unique features of HSC gene therapies. Sometimes referred to as the “last frontier” of medicine, the brain is where some of our most difficult and long-standing therapeutic challenges lie.
  • Better scientific tools – After decades of working on HSC gene therapy, the industry has refined the systems used to modify cells, the processes used to treat patients and the analytical methods used to measure success. During the hearing, scientists were able to discuss in detail, for example, not only whether inserted genes were being expressed but precisely where in the genome they had taken up residence. Standardizing these tools and processes is essential to accelerating the development, regulatory review, as well as delivery of gene therapies to patients.

The learnings from the hearings are further building blocks that could help create a pathway to taking gene therapies mainstream, rather than keeping them sectioned off for ultra-rare diseases. If the FDA approves these two gene therapies later this year, it will bring us to four gene therapies approved in the U.S. in five years. Europe is setting the pace for regulatory approvals of gene therapies, with six gene therapies approved to date.i And there are a couple of additional gene therapies that either have been submitted, or are expected to be submitted by year end, for FDA consideration.

This progress is further reason for celebration, for sure. But as an industry, we need to keep pushing for more. In the development of game-changing monoclonal antibodies, it has taken more than 30 years of blood, sweat and tears to test, modify and switch out elements to build an industry with dozens of approved therapies and an annual global sales revenue of $163 billion, representing about 70% of the total sales for all biopharmaceutical products.ii

I hope my industry colleagues agree that we need to do more, and faster, to emulate that progress and increase the number of patients and families who can potentially benefit from gene therapy.


[i] Gene Therapy Medicinal Products with a valid marketing authorisation – Paul-Ehrlich-Institut (pei.de)

[ii] MAb Products: Market Trends and Projections – BioProcess InternationalBioProcess International (bioprocessintl.com)