For developers of cell and gene therapies, the path to market often seems to be marred with potholes. The FDA rejected BioMarin Pharmaceutical’s gene therapy to treat hemophilia A in 2020, citing the need for more durability data and sending the company’s shares down more than 20% in a day. In November of this year, the FDA delayed a much-anticipated decision on multiple myeloma CAR-T candidate cilta-cel from Legend Biotech and Johnson & Johnson, causing Legend’s stock to fall nearly 8%.
Now, those companies are preparing for the FDA to finally hand down its rulings—and they’re making those preparations optimistically. Biomarin expects to submit new data on its gene therapy, Roctavian, to the FDA in 2022, setting up a potential approval by the end of the year. And, at this year’s American Society of Hematology (ASH) meeting, Legend and J&J rolled out such positive survival data from their cilta-cel trial that some analysts suggested—if it’s approved in February as expected—it could have an edge on Bristol Myers Squibb’s rival CAR-T Abecma.
A rocky trip to marketability is par for the course in cell and gene therapy, but for those companies that endure the bumps, the payoff can be significant. That’s why in spite of the pushback—not just from regulators, but from payers, too—several companies are expected to bring in high revenues from their cell and gene therapies in 2022. At the same time, they’ll be working behind the scenes to boost profitability by improving the complex manufacturing processes necessary to support these pricey therapies.
“There’s a high level of investment in people, quality and safety monitoring, and the effort to dive deeper into the science,” said Ken Mills, CEO of Regenxbio, maker of viral vectors for gene therapy, in an interview. Upcoming launches and the continued global rollouts of previously approved products will bring cell and gene therapy “more into the public consciousness in 2022, and it will just keep building,” he predicted.
There are five FDA-approved CAR-T treatments for blood cancers and two gene therapies to treat rare diseases now on the market in the U.S. The late-stage pipeline could produce several more cancer CAR-Ts and gene therapies to treat a range of diseases.
One of the biggest races to watch in the cell therapy space will be that between Gilead Sciences’ Yescarta and Bristol Myers Squibb’s Breyanzi, both of which are gunning to move their CAR-Ts into earlier lines of treatment in large B-cell lymphoma (LBCL). At ASH, both companies rolled out impressive data from their trials in the second-line setting, but Gilead could have the upper hand by virtue of its three-year head start in the market, analysts said. Gilead expects to hear from the FDA on a label expansion in the second-line setting in April.
“We believe the totality of the data will help further grow adoption of CAR-T therapy for [Gilead], and expansion into the second-line setting … could double the market opportunity,” said RBC analyst Brian Abrahams in a note to investors during the ASH meeting. RBC estimates that Gilead’s total cell therapy revenues—it also markets the CAR-T Tecartus—will rise from $871 million in 2021 to $1.1 billion in 2022.
In the gene therapy market, Roche’s Luxturna for inherited retinal dystrophy and Novartis’ Zolgensma for spinal muscular atrophy (SMA) are making headway, with Zolgensma charting steady growth so far. Jefferies analysts estimate sales of Zolgensma will rise from $1.3 billion in 2021 to $1.6 billion in 2022 and peak at $2.75 billion.
But reimbursement remains a challenge for all makers of gene therapies. Spark, which was bought by Roche in 2019, made waves with its initial list price of $425,000 per eye for Luxturna. Novartis left the gate with Zolgensma priced at $2.1 million. Both companies have dabbled in alternative payment models—Novartis set the bar with an outcomes-based arrangement for its CAR-T, Kymriah, with the Centers for Medicare & Medicaid Services—but the impact of such arrangements on uptake remains a question mark.
Novartis CEO Vasant Narasimhan said during the company’s third-quarter earnings conference call that Zolgensma is seeing strong uptake in the U.S., Germany, Italy and the U.K., and he predicted reimbursement arrangements in Russia and smaller European countries would fuel overseas sales. “So, if we look ahead, we see four key drivers of future growth,” he said, citing new markets, increasing rates of newborn screening for SMA, a study in Europe that “aims to drive confidence in Zolgensma's value across the full EU label” and the potential for intrathecal dosing of the product.
But not all makers of gene and cell therapies are so optimistic. In August, bluebird bio said it would wind down its European operations after failing to reach a pricing deal with authorities in several countries there for Zynteglo, a gene therapy that won conditional approval from the European Medicines Agency to treat beta thalassemia in 2019. CEO Nick Leschly said in a conference call with investors at the time that the European system was “broken.”
Bluebird will be one of the gene therapy developers to watch in 2022, as Zynteglo for beta thalassemia faces an FDA review. The company will be in a tight race with CRISPR Therapeutics and Vertex, which plan to file their gene-edited therapy, CTX001, for approval by the end of next year.
Other companies that could see their gene therapies break out in 2022? UniQure has bounced back after a safety scare with its hemophilia B treatment, AMT-061. It and its global marketing partner, CSL Behring, could seek approval in the U.S. and Europe in 2022. And three potential gene therapies for Duchenne muscular dystrophy, from Pfizer, Sarepta and Solid Bio, could report pivotal data next year.
What's more, three companies are in a tight race to get gene therapies to treat Fabry disease on the market: 4D Molecular Therapeutics, Sangamo and Freeline Therapeutics. They all posted positive clinical data in the fall. As Evercore analysts put it in a note to clients at the time, it’s “very encouraging to see these programs evolving, with lots still to learn as they evolve and lots more potential applications as the profile of each vector/platform comes into focus.”