Special Edition: Reviewing the advanced therapy pipeline

‘We are on track for a watershed year for approvals of new regenerative medicine and advanced therapies’

By Rachel Arthur

- Last updated on GMT

“2021 has been a year of firsts,” notes ARM. Pic:getty/smshoot
“2021 has been a year of firsts,” notes ARM. Pic:getty/smshoot

Related tags advanced therapy medicinal product Alliance for Regenerative Medicine

2021 could set a record in new product approvals in regenerative medicines and advanced therapies; alongside unprecedented levels of financing. And it’s a trend that looks to continue given the volume of trials ongoing worldwide, according to the Alliance for Regenerative Medicine (ARM).

Four new products have already been approved in the sector this year; meaning the industry could easily surpass the previous record of nine in 2016, according to the organization’s H1 2021 report.

“We are on track for a watershed year for approvals of new regenerative medicine and advanced therapies globally. Decisions are expected on 18 regenerative medicine products across 6 geographies, with 10 of these on products that have never been previously approved in any geography — meaning new product approvals could exceed the record of nine set in 2016.

“Four of these have already been approved: Bristol Myers Squibb’s Breyanzi, bluebird bio and BMS’ Abecma, and Mallinckrodt’s Stratagraft, all approved by the FDA, and bluebird’s Skysona, approved in Europe.

“Three of these products, Breyanzi, Abecma, and Skysona, are gene therapy/gene-modified cell therapies, which means 2021 is likely to be a record year for new approvals of this category of products.

“Decisions are expected this year on four more gene therapy/gene-modified cell therapy products, with the possibility of seven total approvals — which would more than double the previous record of three in 2017.”

Upcoming regulatory decisions include those for Abecma (R/R multiple myeloma) in the EU; Cilta-cel (R/R multiple myeloma) from Legend Bio / Janssen in the EU and US; and GT-AADC (AADC deficiency) from PTC Bio in the EU.

The regenerative medicine and advanced therapies sector completed its best-ever six-month period of financing, raising $14.1bn from January through June this year, according to ARM.

This equates to 71% of the record amount raised in all of 2020, putting the industry on track to surpass last year’s figure.

Financing for cell-based immuno-oncology has reached $6.6bn: for the first time surpassing funding for gene therapy at $6.4bn. Public equity performance for cell-based IO companies has exceeded that of gene therapy companies since mid-2020

2021 'a year of firsts'

Not only is the number of approvals of note: so is the groundbreaking nature of the products involved.

“2021 has been a year of firsts for the sector,” ​notes ARM, the international advocacy organization focused on regenerative medicines and advanced therapies and with 400+ members globally.

“Approvals so far this year include the first two products with RMAT designation to reach the market: Breyanzi​, a CAR-T therapy for relapsed or refractory large B-cell lymphoma, and Stratagraft, a tissue-based therapy for severe burns. Additionally, Abecma​, for the treatment of multiple myeloma, is the first-approved BCMA-targeted CAR-T therapy. Finally, Kite Pharma’s Yescarta became the first CAR-T therapy to receive approval in China.”

With more than 2,600 trials ongoing worldwide in the sector, the industry is ‘on the cusp of an even larger breakout’.

There are currently 1,320 industry-sponsored regenerative medicine and advanced therapies trials ongoing worldwide, according data from ARM and GlobalData, with the Asia-Pacific region acting as a major center of growth for the sector. There is also significant clinical activity driven by academia and other research centers, with an additional 1,328 trials sponsored by non-industry groups (including academic centers and government).

There are 243 trials in Phase 3, including 158 industry sponsored trials and 85 trials sponsored by academic, government or other institutions. These late-stage product candidates are being tested to treat a wide range of indications, including diabetic neuropathy, heart failure, rare genetic diseases, and neuromuscular diseases such as amyotrophic lateral sclerosis (ALS).

The figures also show a geographical shift in activity. There are 558 industry-sponsored trials with sites in the US and 238 in Europe. Since 2018, more than twice the number of trials have started in the US and Asia-Pacific than in Europe. The number of developers in Europe has declined by 4% since 2018, while increasing by 23% in the US and 119% in Asia-Pacific.

Areas to watch: CAR-T, gene editing, iPSCs

The CAR-T field continues to advance, says ARM, noting activity in the area in 2021 is expected to continue in the future.

“In addition to Abecma, the first-approved BCMAtargeted CAR-T therapy, we’re seeing a growing number of clinical readouts from CAR-Ts with BCMA.

“Johnson & Johnson and Legend Biotech announced data from their BCMA-targeted CAR-T therapy cilta-cel​ in June showing a 98% overall response rate and an 80% stringent complete response rate in multiple myeloma, with decisions from the EMA and FDA on cilta-cel expected later this year.

“Data readouts from Precision BioSciences and CRISPR Therapeutics’ respective BCMA-targeted CAR-Ts are also expected later this year. We expect this trend to continue as developers look to use CAR-T therapies to treat a broader range of liquid and solid tumors.”

CD19 CAR-T therapies are another area to watch, with more long-term data now emerging. “Originally approved for patients who have not responded to two or more lines of treatment, these therapies are now being tested as an earlier-stage intervention,"​ notes ARM. 

"Breyanzi and Yescarta both demonstrated statistically significant improvement in event-free survival over chemotherapy plus stem cell transplant in second line relapsed or refractory large B-cell lymphoma. These findings suggest that CAR-T therapies may be used as an earlier line of treatment moving forward.”

Gene editing also continues to advance in the clinic.

“Intellia Therapeutics made headlines this summer when it announced promising clinical data from a trial for transthyretin (ATTR) amyloidosis — the first data from an in vivo CRISPR therapy. NTLA-2001 reduced serum levels of transthyretin, a harmful liver protein, by 87%, besting standard-of-care therapies that typically reach 80%.

“We also received additional data from CRISPR Therapeutics and Vertex Pharmaceuticals for their gene-editing therapy for sickle cell disease. All 15 beta thalassemia patients treated were transfusion independent, and all seven sickle cell disease patients were free of vaso-occlusive crises. Outside of the CRISPR space, LogicBio reported that it dosed the first patient in a trial using its homologous recombination gene editing technology to treat methylmalonic acidemia. The trial is reported to be the first in vivo gene editing trial in a pediatric patient.”

Also entering the clinic are induced pluripotent stem cells, or iPSCs: an area of high interest given they can be grown indefinitely and differentiated at large scale.

“Those factors make iPSCs a strong target for largescale, universal or “off-the-shelf” therapies. These therapies are beginning to be tested in a variety of indications. This includes Bluerock Therapeutics’ therapy candidate for Parkinson’s, which was administered to the first patient in a clinical trial earlier this year, as well as Fate Therapeutics, which will share interim data from its PSC-derived NK cell therapy for B cell lymphoma this month. As the field continues to advance, developers seek to work with regulators to set standards for this new technology.”

The full report can be found here.

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