Takeda’s Allogeneic Stem Cell Therapy Becomes First of Its Kind to Be Approved in Japan

Alofisel (darvadstrocel), developed by Takeda, has become Japan’s first approved allogeneic stem cell therapy.

The nation’s Ministry of Health, Labor, and Welfare (MHLW) gave the nod to Alofisel for the treatment of complex perianal fistulas in patients with non-active or mildly active Crohn’s disease. It will be given as a second-line treatment for patients who have not responded well enough to conventional or biological medicines.

The approval is based on supporting evidence from two trials: the Japanese Study Darvadstrocel-3002 and the ADMIRE-CD trial, which took place in Europe and Israel.

Treating Anal Fistulas with Stem Cells 

A fistula is an abnormal channel that connects two separate organs, which develops in some diseases. Some patients with Crohn’s disease develop fistulas that connect lower parts of their gut, such as the anal channel or the rectum, with the skin near the anus. Fluids may leak from the openings, making infection likely. Fistulas can cause intense pain, bleeding, swelling, and anal discharge.

Alofisel uses stem cells derived from the adipose (fatty) tissue of a healthy donor. The regenerative cells, when injected near the fistula, are expected to close the opening.

Alofisel is a made-to-order treatment with a shelf life of 72 hours. The area around the fistula is cleaned prior to the administration of Alofisel. A needle delivers four vials worth of the drug suspension in small blebs, or fluid-filled pockets, inside the walls of the fistula. The stem cells are expected to grow and seal the fistula. 

The 52-week Phase 3 ADMIRE-CD trial, which enrolled 212 patients with perianal fistulas, supported Alofisel’s efficacy. At 24 weeks, 55% of patients treated with the drug were in clinical remission (clinical closure of all treated fistula), compared to 42% in the control group.

The most common side effects associated with Alofisel are anal abscess, where pus fills infected cavities near the anus or rectum, pain from muscle spasms, and anal fistula. The side effects mainly occur in the initially treated fistula, which may reflect a lack of efficacy of Alofisel instead of a safety issue.

Other Approvals (and Setbacks) for Alofisel

Besides Japan, Alofisel is approved in the EU, Switzerland, Israel, and the UK. In the US, the drug is currently under review by the FDA.

Due to the complexity of producing stem cells, the drug could carry a hefty price tag of around $70,000 per course of treatment. The high price failed to convince the National Institute of Health and Care Excellence (NICE), which analyzed the cost-effectiveness of Alofisel and concluded that the drug only provided modest clinical benefit.

Following NICE’s verdict, the Scottish Health Consortium refused to recommend the drug for reimbursement within the National Health Service in Scotland. Despite the setback, Takeda introduced a value-based pricing scheme in Europe in 2019, saying it will reimburse the costs for patients who did not benefit from treatment.

In Takeda’s quarterly financial report ending June 30, 2021, the company reported sales of Alofisel was 388 million yen (around $3.5 million), up from 11 million yen in 2020. The company has a long way to go before it can turn a profit for Alofisel. Takeda acquired Alofisel’s developer, Belgian biotech TiGenix, for over $600 million in July 2018.

Author

Joy Lin

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