Stem Cell Therapy: New Hope for Complex Fistulas
Darvadstrocel (brand name Alofisel) is a new innovation for the allogeneic stem cell therapy which provides an unique option for new and minimally invasive treatment for complex perianal fistulas in adults with Crohn’s disease. Crohn’s disease is a long term condition which creates inflammation in the digestive system or the gut. It affects the lining of the bowel and may also go deeper in the bowel wall. Perianal fistulas are common complications of Crohn’s disease. It is generally caused when an abnormal passageway is created between the rectum and outside of the body.
It can lead to incontinence which is a lack of control over the opening of the bowels and blood infection. Complex fistulas are more resistant in the treatment than the simple fistulas. At this moment, there is no perfect treatment to cure Crohn’s disease. Therefore, the main objective is to stop the inflammatory process, relieve symptoms and avoid surgery. It can affect people of all ages but the young generation is more prone to this.
Alofisel is an allogeneic stem cell therapy which is approved by the EU for the treatment of complex perianal fistulas among adult patients with the symptoms of non-active or mildly active luminal Crohn’s disease. These fistulas have shown an inappropriate response for at least one conventional or biological therapy. However, alofisel should be taken only after conditioning of the fistulas. It is crucial to consult with a fistula specialist doctor near you before taking any therapy.
Also read: Role of Gut Health and Nutrition in Preventing Recurrent Fistula!
Authorization and Composition of Alofisel
The preliminary authorization of alofisel was based on the results obtained from the Phase 3 ADMIRE-CD placebo-controlled registrational study. The size of the population for this study was 212 and modest benefit observed in the ADMIRE-CD study. It shows a difference of 15.8% between the modified intention-to-treat population versus placebo at 24 weeks. After 24 weeks of treatment it is observed that half of the patients who were treated with Alofisel (49.5%) were in remission. On the other hand, a third of the patients were treated with placebo. An extended ongoing follow-up study, which will cover a period of up to 104 weeks of treatment, has supported this result to date.
It is identified that the active element of Alofisel is darvadstrocel. Darvadstrocel contains expanded adipose stem cells which, once activated, impair proliferation of lymphocytes. It further declines the rate of the release of pro-inflammatory cytokines at inflammation sites. This particular activity reduces the inflammation and allows the tissues around the fistula tract to heal properly. Although there is a slight difference between the treatment groups, it is considered to be clinically meaningful when other treatment options have failed significantly. The most common side effects observed include anal abscess and fistula, as well as procedural pain and proctalgia.
Marketing Authorization
Takeda Pharmaceutical Company Limited (TSE: 4502) and TiGenix NV (Euronext Brussels and NASDAQ: TIG) announced on 15th December, 2017 that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) along with the Committee for Advanced Therapies (CAT) has adopted a positive opinion recommending a marketing authorization (MA) for investigational compound Cx601 (darvadstrocel).
It is expected to be indicated for the treatment of complex perianal fistulas among adult patients with the symptoms of non-active or mildly active luminal Crohn’s disease. These fistulas have shown an inappropriate response for at least one conventional or biological therapy. This recommendation marks the first allogeneic stem cell therapy to receive a positive CHMP opinion in Europe.
The product was assessed by the CAT, the EMA’s specialized scientific committee for Advanced Therapy Medicinal Products (ATMP) like the gene or cell therapies. The positive opinion was based on the outcomes generated from the pivotal trial of TiGenix’s Phase III ADMIRE-CD. The ADMIRE-CD trial is a randomized, double-blind, controlled, Phase III trial which is designed to investigate the efficiency and safety of the investigational compound named Darvadstrocel. The 24- week result suggested that Cx601 achieved statistically significant superiority. It is in comparison to the control group in the primary efficiency endpoint of combined remission.
Additionally, the rates and types of treatment related to the adverse events and number of discontinuations due to the adverse events were comparable between Cx601 and control arms. The most common of which were anal abscess and proctalgia. Further follow-up data indicated that Cx601 maintained long-term remission of treatment refractory complex perianal fistulas in patients with Crohn’s disease over 52 weeks.
Mechanism and Application
Active Ingredient
Darvadstrocel is known as the suspension of the expanded human allogeneic adipose-derived mesenchymal stem cells (eASCs) which is obtained from the fat tissue of the healthy donors.
Mechanism of Action
The product is directly injected into the fistula tissue. These stem cells decline the rate of local inflammation and develop an anti-inflammatory microenvironment. The environment facilitates tissue repair and healing of the fistula tract.
Administration
It is a single-dose, local injection procedure operated after the fistula has been surgically conditioned. It often involves temporary seton placement and suturing of the internal opening.
Target Population
It is specifically indicated for the complex perianal fistulas among adult patients with the symptoms of non-active/mildly active luminal Crohn’s disease. These fistulas have shown an inappropriate response for at least one conventional or biological therapy.
Efficiency and Impact
Clinical Efficiency
Pivotal clinical trials (ADMIRE-CD) showed us that after 24 weeks of treatment it is observed that half of the patients who were treated with Alofisel (49.5%) were in remission. On the other hand, a third of the patients were treated with placebo. An extended ongoing follow-up study, which will cover a period of up to 104 weeks of treatment, has supported this result to date. Real-world studies have reported clinical remission rates of over 60% in some cases.
Improved Quality of Life
Complex perianal fistulas have significantly influenced the quality of life because of pain, discharge and activity restriction. Darvadstrocel offers a potentially sphincter-sparing option. It avoids the high risk of incontinence which is associated with some traditional surgical processes. It is crucial to consult with a fistula specialist doctor around you before taking any new medication.
Safety Profile
The stem cell therapy possesses a favorable safety profile where the most adverse events are local and mild to moderate like abscess or proctalgia. These are often related to the process itself.
The European market status has changed but the darvadstrocel has produced an effective stem cell therapy which has offered new hope among many patients with the help of debilitating and treatment-refractory complex perianal fistulas with the help of the promotion of lasting healing option where other options have failed. It is crucial to consult with a fistula specialist doctor for these kind of treatments. Dr. Azhar Alam, who is a fistula specialist doctor in Kolkata, needs to be consulted for this purpose.
