Gene Therapy Remains On Course To Broadly Transform Medicine

By Geoff MacKay, President and CEO, AVROBIO

When we founded AVROBIO seven years ago, we asked ourselves the question – What if one gene can change your entire world? Every year that question reinvigorates our resolve to develop an answer: a single infusion gene therapy with the potential to alter the downward trajectory of certain genetic diseases. This year, as we review achievements from 2022 and define priorities for the year to come, we see plenty of hurdles to clear, most prominently the ongoing diffidence of the financial markets. However, we believe the future of gene therapy shines bright.

With the industry seeing five gene therapy approvals in 2022 and 30 gene and genetically modified therapies in Phase 3 in the last quarter, there is clear momentum in the field. And with nearly a dozen anticipated regulatory decisions on the horizon in 2023, that momentum is poised to accelerate.

That progress is a potential good indicator of improving prospects for the field. The Gartner curve, used by analysts to visualize the adoption of new technologies by businesses, describes a “slope of enlightenment,” which comes after initial excitement around an innovation has worn off and companies are doing the hard work of identifying and overcoming obstacles to its adoption. That’s where gene therapy has been in recent years, as we’ve seen solutions emerging for formerly daunting challenges like manufacturing, analytics, and pricing. What follows the slope of enlightenment? It’s the plateau of productivity, where technology goes mainstream.

While I don’t expect the industry to achieve widespread adoption of gene therapy in 2023, we will be much closer a year from now than we are today. As we continue to accumulate real data, real milestones achieved and real patients’ lives dramatically changed, I expect three themes to play out for the gene therapy industry in 2023: 1) how and to what extent regulatory approvals translate into commercial viability; 2) a growing need for differentiation based on innovation; and 3) pipeline and industry consolidation.

Commercial viability

The first theme is perhaps the one that generates the greatest anxiety today among gene therapy players. With more gene therapy companies becoming de-risked as they clear both regulatory and reimbursement hurdles, for the first time we’ll have a chance to observe what it takes for a gene therapy addressing larger patient populations – like BioMarin’s hemophilia A gene therapy, which is currently undergoing FDA review – to be commercially viable.

While there are certain elements that we know are important for a therapeutic to achieve commercial success – including addressing high unmet need, being first to market, having a strong pricing rationale and targeting substantial patient numbers – it will be interesting to learn more about what combination or degree of those elements drive gene therapies forward. Like all health care modalities, there will be winners and losers, but progress through 2023 will provide more clarity on the recipe for gene therapy commercial viability.

Differentiation based on innovation

People will always invest in great science that meets an unmet medical need. That is why having a differentiated approach is critical for gene therapy companies and what may ultimately set the winners in the gene therapy field apart.

This also holds true for scientific innovation. Manufacturing cell and gene therapies is not easy; it is even more challenging to manufacture at scale. As more advanced gene therapies move into the clinic and to commercial stage in 2023, having a robust manufacturing process, having that process be scalable will likely be increasingly important. Innovation has been central in the building of AVROBIO, including our approach to manufacturing, and we bring that focus into 2023. plato® is designed as an end-to-end solution covering vector design and vector production, drug product manufacturing, as well as analytics.

The automated nature of our plato platform is designed to improve consistency and product quality, promote scalability, and reduce cost of goods. Frozen vector can be stored for at least five years, addressing future demand for late-stage development and potential commercialization. And our centralized analytical approach means that assays used to determine elements such as transduction and potency are leveraged across the platform.

Pipeline and industry consolidation

Finally, market headwinds are bound to force further pipeline and industry consolidation in 2023. Unfortunately, there is a major disconnect between the gene therapy field’s progress and investments. The positive clinical data, multiple regulatory approvals, and strong pricing achievements we have seen over the past 12 months have yet to translate to public equity markets. It may take a long time for the investor community to recalibrate.

It is estimated that more than 200 biotechnology companies are now trading below their cash positions, and that means intensified strain for many gene therapy companies. As a result, this year will continue to see restructurings, pipeline reprioritizations, collaborations and, increasingly, bankruptcies. I believe that companies built on great science will persevere, but, in the short term, it will be companies with nimble business models to advance that great science that will best navigate this austere financial climate.

As these three themes intersect in the upcoming year, it will be interesting to see how they continue to shape the gene therapy field. Are they the right developments, at the right time, that will push one-time gene therapies to change the world of more patients and families living not only with rare genetic diseases but also diseases with larger patient populations, like heart disease and diabetes? What the field will look like a year from now is anyone’s guess, but every hard-fought win moves gene therapy forward on its course to broadly transform medicine.

Geoff MacKay is the president and CEO of AVROBIO, a leading clinical-stage gene therapy company with a shared vision to bring personalized gene therapy to the world. He is a pioneer in cell and gene therapy with a track record of successful leadership at innovative biotechs. He is the former CEO of Organogenesis Inc., the world’s leading cell therapy company. During his tenure at the helm, the company treated 1 million patients with living cell therapies, received the first approval of an allogeneic cell therapy from the FDA’s Center for Biologics Evaluation and Research and led the field of regenerative medicine. Geoff is also the founding CEO of eGenesis, a biotech dedicated to applying CRISPR-Cas9 gene editing to xenotransplantation. Earlier in his career, Geoff spent 11 years at Novartis in senior leadership positions within the global transplantation and immunology franchise. Geoff sits on the boards of Talaris Therapeutics and Satellos Bioscience. Past activities include chairman of the board of MassBio, chairman of the board of the Alliance of Regenerative Medicine, and a member of the advisory council to the Health Policy Commission for Massachusetts.