CAR-T approvals marred by autologous manufacturing limitations, says Allogene

Autologous therapies have not kept up with demand says Allogene Therapeutics, which claims only off-the-shelf cell therapies can serve larger patient populations.

While the approval of Novartis’ Kymriah (tisagenlecleucel) in 2017 marked a breakthrough for chimeric antigen receptor (CAR) T-cell therapies, the sector has been slow to blossom. However, the past year or so has seen some breakthroughs in the space: Approvals for Bristol-Myers Squibb’s Breyanzi (liso-cel) and Abecma (ide-cel), and J&J’s Carvykti (ciltacel). Meanwhile, last month Gilead’s Yescarta (axicabtagene ciloleucel) was approved by the FDA as a second line treatment for adults with large B cell lymphoma.

These are meaningful advances that will change the practice of medicine and stoke further investment in the sector, as well as broadening the number of patients who can potentially benefit from CAR-T therapy.

Allogene lauds benefits of off-the-shelf CAR-Ts. Image: Stock Photo Secrets

While these successes have been applauded by industry, “broader treatment recommendation creates inherent challenges for therapists that must be manufactured and delivered on an individual patient basis,” David Chang, CEO of Allogene Therapeutics has warned.

“The logistical challenges and cost of manufacturing patient by patient, as well as waiting times and potential for manufacture failure, must all be addressed in order for the field to move forward.”

Allogene launched in 2018 with backing from Pfizer to develop allogeneic, or off-the-shelf, CAR-T therapies and Chang’s words came during his firm’s Q1 results call last week.

“Markets like second line large B cell lymphoma and relapsed refractory multiple myeloma are large, consisting of many thousands of potentially suitable patients. Autologus therapies have simply not been able to keep up with demand. Sadly, no matter how efficacious an autologous CAR-T therapy may be, its benefits do not extend to those patients who elect and leave. The recent approval and expected approval of additional indications will place more pressure on the supply bottleneck.”

Chang noted that despite an increase in manufacturing capacity, scalable supply of autologous products is not possible as each production run needs to be individually tailored. “For an autologous therapy to serve 25,000 patients, it must successfully execute 25,000 manufacturing runs.”

Therefore, he continued, “the most efficient way to meet such demand is an allogeneic CAR-T product, which also provides the promise of growing the market.”

The firm’s lead candidate is ALLO-501A, in Phase I/II trials for non-Hodgkin lymphoma. According to Chang, Allogene can make 20,000 patient doses annually at a fraction of the number of manufacturing runs it would take for an equivalent number of autologous doses.

“We think this type of step function improvement in both efficiency in production and speed of treatment will be a requisite for treating the large number of patients who stand to benefit from CAR-T therapy.”