Source: European Medicines Agency (EU) Revision Year: 2020 Publisher: Takeda Pharma A/S, Dybendal Alle 10, 2630 Taastrup, Denmark
Hypersensitivity to the product, bovine serum or any of the excipients listed in section 6.1.
In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.
Alofisel may contain trace amounts of benzylpenicillin and streptomycin. This should be considered in patients with known hypersensitivity to these classes of antibiotics.
Local anaesthesia is not recommended due to the unknown effect of local anaesthetics on the injected cells (see section 4.2).
The injection of any substance other than sodium chloride 9 mg/mL (0.9%) (e.g. hydrogen peroxide, methylene blue, iodine solutions or hypertonic glucose solutions) (see section 4.2 and section 4.5) through the fistula tracts is not allowed before, during, or after the injection of Alofisel as these may compromise the viability of the cells and, therefore, may affect the effectiveness of the treatment. Alofisel is indicated only for injection in the fistula tract tissue as described in section 4.2. Alofisel must not be administered using a needle thinner than 22G. Thinner gauge needles can cause cell disruption during injection and may compromise cell viability and, therefore, may affect efficacy of treatment.
As Alofisel is a living stem cell therapy it cannot be sterilised, and therefore could contain potentially infected biological material although the risk is considered to be low and controlled in the manufacturing. Patients should be followed up for potential signs of infection after administration.
Conditioning of fistulas has been associated with proctalgia and procedural pain (see section 4.8).
No in vivo interaction studies have been performed.
In vitro interaction studies have shown that the cell viability and immunomodulatory function of Alofisel is not affected by the presence of clinically-relevant concentrations of conventional therapies for Crohn’s disease (infliximab, methotrexate and azathioprine).
The injection of any substance other than sodium chloride 9 mg/mL (0.9%) (e.g. hydrogen peroxide, methylene blue, iodine solutions or hypertonic glucose solutions) (see section 4.2 and section 4.4) through the fistula tracts and use of local anaesthesia is not recommended due to the unknown effect on the injected cells (see section 4.4).
There are no data from the use of darvadstrocel in pregnant women. Animal studies are not available with respect to reproductive toxicity (see section 5.3). Darvadstrocel is not recommended during pregnancy and in women of childbearing potential not using contraception.
As a precautionary measure, darvadstrocel is not recommended for administration during breast-feeding.
No data are available.
Darvadstrocel has no or negligible influence on the ability to drive and use machines.
The most common treatment-emergent adverse events were anal abscess (Alofisel: 19.4% patients; control group: 13.7% patients), proctalgia (Alofisel: 14.6% patients; control group: 11.8% patients) and anal fistula (Alofisel: 10.7% patients; control group: 7.8% patients).
The following listing of adverse reactions is based on the clinical trial experience and is displayed by system organ class. The frequency of adverse reactions is defined using the following convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000) and not known (cannot be estimated from available data).
Table 1. Adverse reactions:
Common: Anal abscess
Common: Proctalgia*, Anal fistula
Common: Procedural pain*
* Conditioning reactions occurring up to seven days after the fistula cleaning for treatment administration.
Up to Week 52, 20 (19.4%) and 14 (13.7%) patients developed 21 and 19 anal abscess adverse events in the Alofisel and control groups, respectively, of which 4 and 5 adverse events in respective groups (3.9% patients in both groups) were of severe intensity. Up to Week 104, 15 (14.6%) and 8 (7.8%) patients developed 15 and 9 serious adverse events of anal abscess in the Alofisel and control groups, respectively.
Up to Week 52, 15 (14.6%) and 12 (11.8%) patients developed 20 and 17 proctalgia adverse events in the Alofisel and control groups, respectively, none of these events being serious in any group up to Week 104. There were no patients in Alofisel group with events of proctalgia of severe intensity and 3.9% patients with 4 events in the control group.
Up to Week 52, 11 (10.7%) and 8 (7.8%) patients developed 12 and 8 anal fistula adverse events in the Alofisel and control groups, respectively, none of these being of severe intensity. Up to Week 104, 5 (4.9%) and one (<1.0%) patients developed 5 and 1 anal fistula serious adverse events in the Alofisel and control groups, respectively.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
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