When drugs enter into clinical studies, both patients and drug developers alike hope for success. These therapies could transform the treatment sphere, especially in disease states with limited or no existing treatment options. When Takeda Pharmaceuticals began its Phase 3 ADMIRE-CD II trial evaluating Alofisel (daradstrocel) for complex perianal fistulas (CPF), a complication of Crohn’s disease, the company had high hopes for the injectible stem cell therapy. 569 patients with complex perianal fistulas enrolled in the study.
Unfortunately, reports Kevin Dunleavy in Fierce Pharma, Alofisel fell short. By 24 weeks, the therapy failed to meet its primary endpoint (combined remission). Takeda has shared this failure but has not yet shared the study data, choosing to wait until a later date.
Does this mean that Takeda will stop working towards Alofisel approval in the United States? At this time, there are no clear answers to this question. Takeda is currently assessing the financial impact of the study and will share, at another point in time, its future plans.
While Alofisel’s future in the United States remains uncertain, the drug has been approved for use in Japan, the United Kingdom, and the European Union (EU) for people with complex perianal fistulas who have not responded to prior treatment.
About Complex Perianal Fistulas (CPF)
The perianal region is the area around the anus. People with Crohn’s disease have ulcers that form in their digestive tracts. Sometimes, these ulcers break through the intestines and form tunnel-like structures (fistulas) that connect the intestine to perianal skin or muscle. According to the Global Healthy Living Foundation, an estimated 33% of people with Crohn’s disease will develop perianal fistulas. The GHLF also notes that perianal fistulas are considered complex if they:
- Involve a large part of the sphincter muscle, which opens and closes the anus
- Branch or have more than one opening into muscle or skin
- Become infected or form a pus-filled sac inside called an abscess
- Involve the rectum or vagina
- Are in a person with inflammatory bowel disease, fecal incontinence, chronic diarrhea, or anorectal cancer (not all doctors and guidelines use this definition of complex)
People with CPF may experience rectal and anal pain, fever, redness and inflammation near the fistula, and blood or pus around the fistula. The best CPF treatment involves a mixture of medications such as azathioprine and methotrexate alongside surgical interventions. According to the GHLF, the best treatment is a seton placement, or a type of minor surgery that allows the fistula to drain and heal.
In some cases, other more complex surgeries may be required. If you have a complex perianal fistula, please speak with your doctors about the best course of treatment.