Gene Therapy

Cell and gene therapies achieved record growth in 2020, surpassing prior high points in terms of financings and approvals. Janet Lambert, CEO of the Alliance for Regenerative Medicine (ARM), painted a rosy picture despite a few challenges at the 2021 Cell & Gene State of the Industry Briefing during this year’s Biotech Showcase, held virtually January 11-15.

“2020 was a record-shattering year for financing, with $19.9 billion raised in 2020, up from the $9.8 billion raised in 2019 and the $13.3 billion raised in 2018 – the previous record,” she said.

Follow-on financings, at $6.8 billion, accounted for the largest portion of funding, followed by venture capital at $5.6 billion and IPOs at $3.7 billion. Upfront payments from partnerships totaled $3 billion and private placements totaled $1.2 billion.

The number of large financings exceeding $200 million grew noticeably. Sana Bio’s $700 million private financing, announced last June, topped the field. Iovance and bluebird bio gained the most from follow-on financing, with fundings of $604 million and $575 million, respectively. Legend Bio led the list of IPOs, raising $487 million last May.

“Large pharma continued to buy-in to biotechs for research, development, commercialization, and licensing agreements focuses largely on oncology and CNS disorders,” Lambert said. She cited Sangamo, with two major collaborations with Biogen ($350 million) and Novartis ($75 million), though adding, “Bayer is especially active.”

In the stock market, “Regenerative medicine companies outperformed the NASDAQ Biotech Index,” she continued. Although stock prices for virtually everything plummeted in mid-March, biotech stocks rebounded. “Cell based immuno-oncology (IO) share prices increased 80% from their January 1 levels. Gene therapy was close behind, with a 70% increase, and all publicly traded regenerative medicine companies saw a 50% increase.”

Given the overall environment, it seems safe to predict that 2021 will be another good year for regenerative therapies.

Currently, there are approximately 1,100 gene, cell and tissue-based therapeutic developers throughout the world. Of those, the overwhelming majority are in North America, with 543. “We saw a lot of growth in China, Japan, and Korea,” she said, with 295 companies. Europe boasts 209.

Globally, 1,220 clinical trials are underway for regenerative medicine.

“More than 100 clinical trials commended in the fourth quarter alone,” Lambert said. “Roughly, they are divided evenly among cell, gene, and IO. With 152 trials in phase III and nearly half of those in gene therapy, this offers strong support for predictions by both the FDA and EMA that there will be 10 to 20 advanced therapies approved each year through 2025.”

What people often forget, Lambert said, quoting Amy Price, a mother of two gene therapy recipients, is that cell and gene therapies aren’t “some fantastical futuristic thing.” Two of the Price children received gene therapy in a clinical trial 10 years ago for metachromatic leukodystrophy (MLD), a historically fatal disease. That drug, Libmeldy™, by Orchard Therapeutics, was approved in Europe in 2020, making it one of the most significant milestones of the year.

The benefits of cell and gene therapy have expanded beyond experimental treatments.

“Patients are continuing to benefit from innovative therapies,” Lambert said. “We saw a significant number of gene therapy approvals in 2020.” In addition to Libmeldy, she cited approvals of Zolgensma® (by Novartis Gene Therapies) in Europe, Japan, and Canada; Tecartus™ (by Kite, a Gilead company) in the U.S.; and Luxturna® (by Spark/Roche) in Canada.

Looking forward, oncology, and particularly IO, dominates the regenerative medicine landscape. Some 554 oncology trials are underway.

“Investors have invested heavily in this space for some time, and IO comprises 50% of Phase I trials in cell and gene therapy,” Lambert noted. Focus is increasing on allogeneic therapies as well as gene editing.

Central nervous system therapeutics are the second most popular therapeutic indication for regenerative therapies for the second year in a row, with 94 trials. 2020 saw promising data from the first-ever attempt iPSC therapy for Parkinson’s disease.

“Gene editing continues to advance in the clinic,” she added. “For the first time, a patient was treated with CRISPR therapy in vivo and, later, systemically with CRISPR. CRISPR Therapeutics and Vertex Pharmaceuticals shared data (during J.P. Morgan week) from a sickle cell trial of 20 patients.”

Despite these scientific advances and investor enthusiasm, cell and gene therapies face challenges in terms of dosing and delivery, and chemistry, manufacturing and controls (CMC), Lambert admitted. “Gene therapy represents almost half of the Phase III pipeline, so we expect to learn a lot quite soon.”

While it goes without saying that 2020 was a challenging year, many of the repercussions of the COVID-19-related disruptions remain to be seen. They extend not only to operational and clinical disruptions but also to regulatory backlogs and the politicization of diagnostics and therapeutics, all set against the usual challenges of fast-moving science.

None-the-less, Lambert pointed out, “There were some positive developments.”

As she said, Medicare approved a new diagnosis related group (DRG) for CAR T cell therapy and promulgated a new rule for outcomes-based therapies, thus enabling a new payment model that ARM deems essential for cell and gene therapies. In Europe, the European Commission’s pharmaceutical strategy now recognizes the importance of cell and gene therapy. “We are encouraged that we can build on that starting point with the Commission,” Lambert said. ARM also is expecting progress on n-of-one therapies for ultra-orphan indications this year.

Looking ahead to 2021, Lambert identified six regenerative therapies on the FDA’s docket from Mallinckrodt, bluebird, BMS, PTC Bio, and Gensight Bio. “All indications are that 2021 will be a fantastic year of scientific, technological, and clinical progress in this sector,” Lambert predicted.



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