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Scaling the slope of enlightenment: Gene therapy progress and the future of healthcare

President & CEO

Geoff MacKay | President & CEO

The gene therapy industry is undergoing a regulatory resurgence. After three years with no new therapies reaching patients in the United States, two approvals in the last two months – of hematopoietic stem cell (HSC) gene therapies for beta thalassemia and cerebral adrenoleukodystrophy – have doubled the number of gene therapies available here. Across the Atlantic, two gene therapy approvals this summer by the European Commission – gene therapies for severe hemophilia A and aromatic L-amino acid decarboxylase (AADC) deficiency – are positioned to further transform medical care for patients.

And all indicators are that we can expect this cadence to continue. Several companies are expected to file for approval over the next 12 months, and more than 39 gene therapies are currently in Phase 3 clinical trials.

While the financial markets remain repressed, these successes are rightly seen as a sign of improving prospects for gene therapy. I see them as a reflection of increasing adoption that over time has the potential to dramatically change our entire healthcare system. The tech industry often uses a model for the adoption of new technologies called the Gartner® curve, which describes a “slope of enlightenment” that comes after the initial excitement around an innovation has worn off and the obstacles to applying it have become clear. Companies climb the slope of enlightenment by overcoming these challenges to create a formula for success. I believe the gene therapy sector is starting the climb up the slope of enlightenment. As that happens, we can expect to see more gene therapies for more diseases reaching more patients and even changing the face of healthcare across a broad spectrum of rare diseases – and perhaps some not-so-rare diseases, as well.

The evidence of momentum is not just measured in recent approvals, but also in other regulatory milestones, clinical data, manufacturing advances and commercial developments. Our field progresses as gene therapy accumulates real data, real regulatory milestones and stories of real patients’ lives dramatically changed.

In the clinic for example, the dramatic potential of gene therapy is turning into reality as patients go months and then years without needing the chronic treatments they once relied upon to help manage their disease. We have seen and heard more case studies of gene therapies slowing or stopping the course of progressive, fatal genetic diseases, leading to talk of “functional cures.” And importantly, while there have been some exceptions, the overall safety profile of gene therapies has advanced to be generally more predictable and understood.

The chemistry, manufacturing and controls (CMC) side of gene therapy has advanced too, with manufacturing no longer the showstopper it was once feared to be. When Spark Therapeutics developed LUXTURNA®, the first gene therapy approved in the United States, it had to create virtually everything from scratch. Assays, manufacturing, clinical and regulatory pathways all had to be invented, the company’s former head of technical operations, Diane Blumenthal, once wrote. But five years down the road, those trails through the wilderness have become familiar terrain. Innovations like AVROBIO’s plato® platform, an automated process that is designed to incorporate everything from vector design to manufacturing, from drug product testing to delivery, have been built to be scalable to support late-stage clinical development and future commercialization for successive gene therapy programs.

These clinical and technical advances have been matched on the regulatory side by a clearer path to approval for more patients. Feedback from regulators has been consistent, and a pattern around how regulators will evaluate the risk/benefit of gene therapies has started to emerge. In the face of urgent unmet needs among patients, this insight is giving more companies the confidence to request creatively designed accelerated approval pathways, including Sarepta Therapeutics for their Duchenne gene therapy and REGENXBIO for their Hunter syndrome gene therapy.

We have also seen increasing acceptance of the economic and healthcare system value of these gene therapies. For example, in August 2021, bluebird bio announced it was exiting the European market over difficult price negotiations around its beta thalassemia gene therapy, Zynteglo. Eight months later in the U.S., the nonprofit Institute for Clinical and Economic Review reported that the same therapy would be cost effective at a price of up to $2.77 million, opening the door to a small but promising market in the United States. The gene therapy has since been approved by the U.S. Food and Drug Administration (FDA) and is priced at $2.8 million.

There is increasing recognition that this price is well below the typical cost of treating beta thalassemia over a patient’s lifetime (which according to bluebird can reach $6.4 million) for a one-time treatment that directly addresses the root cause of a serious disease, potentially halting its symptoms, progression and lifelong current treatment burden for good. The same is true for BioMarin’s hemophilia A gene therapy: ICER said it would be cost effective up to $2.5 million. When it was approved in the European Union this summer, BioMarin announced a price of around $1.5 million euro. The healthcare system, unaccustomed to applying such powerful tools, will naturally take time to adjust to the advent of this new technology. But gene therapies have already begun to spur that transformation.

The Gartner curve settles into a period called the “plateau of productivity,” which is when a new product starts to go mainstream, seeing widespread adoption and has a clear value proposition. We are not yet there when it comes to gene therapy, but I think we are building the momentum we need to get to that stage over the next few years. The opportunity to dramatically transform the lives of more patients and families, as well as to dramatically change our entire healthcare system, is in our sights.