Alofisel (formerly Cx601) is a stem cell therapy developed by TiGenix for the treatment of complex perianal fistulas in patients with Crohn’s disease (CD), and it represents the first allogenic stem cell therapy to receive a positive opinion from the Committee for Medicinal Products for Human Use (CHMP). The treatment is derived from adipose stem cells, which are delivered locally to the fistula and exert an anti-inflammatory action on the surrounding tissue.
In December 2017, the Committee for Medicinal Products for Human Use (CHMP) issued a positive opinion for TiGenix’s Alofisel, and we expect the European Commission to adopt the CHMP recommendation and grant market approval for this therapy during 2018. In the US, where development started later, we forecast a later launch in 2022, assuming the successful completion of a phase III trial in 2021.
Perianal fistulas─ abnormal tunnels between the anal canal and perianal skin─ are a common complication of CD disease that roughly 20% of CD patients will face during their lifetime (cumulative incidence figure)1. Perianal fistula can result in infections, pain, abnormal discharge, incontinence, and significantly reduce patients’ quality of life. Treatment options include surgery and pharmacological treatment. Surgery is not necessarily a cure, as post-surgery recurrence rates are high. At present, pharmacological treatment options include antibiotics, immunosuppressants and biologics (e.g., TNF-α inhibitors). While TNF-α inhibitors are the current perianal fistula treatment mainstay, they are only moderately effective and a notable percentage of patients lose response over time. Indeed, according to TiGenix estimates, roughly 22,000 adult CD patients in the US are currently suffering from complex perianal fistulas and are refractory to treatment2: for these patients, treatment options are extremely limited.
However, published clinical trial data show that 51.5% of Alofisel-treated patients (n=103) achieved combined remission (defined as clinical remission of the fistula and lack of abscesses) at 24 weeks, and 75% of these patients did not incur in a relapse as of 1-year post-injection3. Given that the clinical trial data supports one-year efficacy with a single dose, we expect that alofisel will be administered as a single dose on a yearly basis. These results raise the possibility that Alofisel will offer a potential treatment for fistulizing CD patients who have failed conventional therapies and biologics.
Nevertheless, despite the exciting clinical data, Alofisel is likely to face market access challenges. The drug has been studied as an add-on therapy to the already expensive TNF-α inhibitors, and is independently likely to carry a relatively high price tag (TiGenix considers price points between $40,000 to $50,000 as conservative, and indicates that optimal pricing would fall between $60,000 and $120,000 per dose2).
If every eligible US patient were to receive one injection/year, the overall cost for the treatment of CD would increase by roughly $900 M/year (assuming conservative pricing). While this cost represents only ~6% of the yearly expenditure for CD, and thus, would have a modest budget impact, on a single patient basis, the cost of care will double, from roughly $35,000 to $75,000 for eligible patients2,4.
As a result, payers are likely to pay close attention to Alofisel’s cost-effectiveness; in order to justify its price point, the stem cell therapy must show an increase in patients’ quality of life, which is typically measured in QALY (where 1 QALY represents 1 year of life in a perfect health status5).
While the US healthcare system does not have a formal threshold for cost-effectiveness, the UK utilizes a threshold of £30,000/QALY (roughly $42,000/QALY)6. Considering the data available so far, and assuming one injection/year, it looks unlikely that Alofisel will meet the NICE cost-effectiveness bar, because Alofisel is not a cure for CD and thus patients will not gain 1 year of perfect health.
However, because Alofisel’s label is expected to cover only 22,000 CD patients, the therapy could be considered a treatment for a rare disease (and indeed, the therapy has obtained orphan status both in US and in EU). For rare diseases, the cost-effectiveness threshold defined by NICE would be £100,000/QALY6 (~140,000/QALY), and under these condition, payers are likely to be more amenable to consider Alofisel as a cost-effective treatment option.
Other parameters that may affect Alofisel’s cost effectiveness evaluation are the durability of its response and the potential cost-savings that could result from the use of the therapy.
While the company has publicly released data spanning one year of follow-up, a longer-term follow-up time of treated patients will provide further insights on the treatment duration: if Alofisel’s efficacy were to be proven more durable, thus improving patients’ quality of life over a longer time-frame, its cost-effectiveness evaluation would definitely be more favorable.
With respect to cost-offsets, the therapy is currently being tested as an add-on to patients’ existing therapies, which already represent the highest expenditure in this patient population7. Consequently, current cost savings are likely to be modest and primarily associated with a reduction in the number of medical intervention necessary to treat perianal fistulas. However, if TiGenix were to prove Alofisel’s effectiveness as a monotherapy (especially in refractory patients), the cost offset that could result from decreased use of high-priced TNF-α inhibitors in this population could, in turn, increase payers’ willingness to favorablely reimburse Alofisel.
Regardless of the affordability challenges that Alofisel may pose, the therapy is currently well positioned to capture a niche segment of CD patients. Moreover, if used to treat other fistulas in both CD and non-CD patients, Alofisel holds the potential to address a much larger patient population (roughly an additional 80,000 patients in the US)2.
As a testimony to Alofise’s market potential, in January 2018 Takeda has announced its intention to acquire TiGenix subject to several conditions, with one condition being Cx601 obtaining marketing authorization in the E.U. from the European Medicines Agency (EMA)8. Alofisel brings an exciting niche therapy to CD patients with complex perianal fistula. More importantly, its adoption will likely open the gates for more stem cell therapies.
Methodology: Alofisel eligibility in US was calculated considering the prevalent CD population (DRG proprietary epidemiology) and Tigenix estimates for the prevalent number of CD patients expected to be included in the label. The average cost to the US healthcare system for fistulizing and non-fistulizing CD are assumed to be, respectively, ~ $ 35K and ~ $ 15K. A conservative estimate for the cost of a single Alofisel injection is ~$ 40K.
Sources: Cohen RD et al, 2008, Chaparro M. et al., 2013, TiGenix corporate presentation, June 2017
- AGA technical review on perianal Crohn’s disease 2003; 125(5):1508-1530
- TiGenix company presentation, June 2017 (http://tigenix.com/wp-content/themes/tigenix/images/TiGenix_Corporate_Presentation.pdf , accessed on June 22nd, 2017).
- Panes J et al. Long-term efficacy and safety of Cx601, allogeneic expanded adipose-derived mesenchymal stem cells, for complex perianal fistulas in Crohn’s disease: 52-week results of a Phase III randomized controlled trial. The 12th Congress of ECCO, February 15-18, 2017, Barcelona, Spain
- Cohen RD et al, 2008. Effects of fistula on healthcare costs and utilization for patients with Crohn's disease treated in a managed care environment.
- Gene therapy: understanding the science, assessing the evidence, and paying for the value: a report from the 2016 ICER membership policy summit. March 2017.
- Chaparro M. et al., 2013 Health care costs of complex perianal fistula in Crohn's disease.
- Takeda’s press release, January 5, 2018.
For more insights on forecast and adoption of current CD treatments, please consult DRG’s 2017 Crohn’s disease landscape & forecast report, we will be updating this content throughout 2018.
For more insights on market access challenges for rare diseases, please consult DRG’s 2017 Orphan Drugs and Rare Diseases | Access & Reimbursement.
Crohn's Disease Landscape & Forecast [Special Topics: Microbiome Therapies for Immune & Inflammatory Diseases]
Rare Diseases and Orphan Drugs [Access & Reimbursement | Detailed, Expanded Analysis Orphan Drugs (EU)]
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