Industry Looks to ‘Lucrative’ Opportunities for Off-the-Shelf Cell Therapies

Allogeneic cell therapies have greater commercial potential than autologous products, an industry survey finds. Respondents also believe there are a lack of third-party capabilities to make these new therapies.

When Novartis’s Kymriah (tisagenlecleucel) received the regulatory thumbs up in August 2017, US Food and Drug Administration (FDA) Commissioner Scott Gottlieb described regenerative medicines as being “no longer the stuff of science fiction.” The approval of Gilead/Kite’s Yescarta (axicabtagene ciloleucel) weeks later helped cement the safety and commercial potential of CAR-T therapies.

But like Dendreon’s cellular immunotherapy product Provenge (sipuleucel-T) – approved to treat prostate cancer in 2010 – Kymriah and Yescarta are autologous products, made from a patient’s own cells.

The cells are extracted, engineered then administered back into the individual. The process is costly and the end-product expensive, with added risks coming from the complex and time-critical supply chain.

It is no surprise, therefore, a state-of-the industry survey found allogeneic – or ‘off-the-shelf’ – therapies have a bigger potential for commercial success than allogeneic ones.

Over 60% of respondents to KNect365 Life Sciences’ recent Cell and Gene Therapy Survey viewed allogeneic therapies as more lucrative. The survey, conducted earlier this year, received input from pharma, biotechs, academia, CDMOs, service providers and regulators.

Lower COGs

With allogeneic cells, the potential patient population will be naturally larger than with personalized therapies. At the same time the ability to manufacture large batches is more in keeping with standard biotherapeutic processes.

Therefore, the cost of goods will be lower and profits theoretically higher. This sits in line with the survey, where 87% of the survey’s respondents said monitoring the cost of goods is either ‘very important’ or ‘extremely important.’

For now Takeda – through its acquisition of Tigenix – is alone in commercializing an allogeneic cell therapy with Alofisel (darvadstrocel) being approved to treat complex perianal fistulas in Crohn’s disease in Europe earlier this year.

Outsourcing Demand

Almost half the respondents (48%) said they manufacture solely in-house, with another 32% saying they make their products both internally and using contract manufacturers.

As with other complex biotherapeutics, firms, where possible, prefer to manufacture in-house to ensure control and compliance of their bioprocesses. For example, Novartis makes Kymriah from its facility in Morris Plains, New Jersey acquired from Dendreon in 2012. Kite makes Yescarta at a custom-built plant in El Segundo, California.

But another key factor could be the relative lack of outsourcing facilities with the expertise to make these newer and often unproven products.

“Manufacturing capabilities needed for autologous cell therapies are not yet common, and most CMOs are not yet competent,” Fiona Barry, associate editor of PharmSource, told BioProcess Insider.

Only around 30 companies are involved in contract manufacturing autologous cell and tissue therapies, her research found.

Demand for cell and gene therapy services has, however, driven several major investments by contract manufacturing organizations (CMOs) over the past year, with Lonza, Brammer Bio, VGXI, Fujifilm, and Paragon Bioservices all announcing new capabilities in the space.