Drug vials and a syringe

The European Medicines Agency (EMA) has recommended marketing authorization for Coagadex to treat hereditary factor X deficiency, a rare bleeding disorder.

The active substance in Coagadex is coagulation factor X, a protein derived from human plasma.

Coagadex is intended to treat and prevent bleeding episodes and control bleeding during surgical procedures in patients with hereditary factor X deficiency.

If the European Commission follows the EMA’s recommendation, Coagadex will be the first specific replacement therapy approved in the European Union (EU) to treat patients with this disorder.

Current treatment for factor X deficiency in the EU includes replacement therapies that contain a mix of coagulation factors. These are associated with dosing problems and the risk of elevating other clotting factors, which may result in complications.

Due to the lack of specific treatment options for factor X deficiency, the EMA’s Committee for Medicinal Products for Human Use (CHMP) decided to speed up the evaluation of Coagadex and recommended marketing authorization following an accelerated assessment. This is one of the agency’s tools to speed up patient access to new medicines if they address an unmet medical need.

The CHMP based its recommendation for authorization of Coagadex on the results of 2 non-randomized studies.

The first trial included 16 patients who received Coagadex for pharmacokinetic evaluation, on-demand treatment and control of bleeding episodes, and/or perioperative management of minor surgical or dental procedures.

Coagadex was used to treat 208 bleeding episodes, and 187 of these episodes (in 15 patients) were evaluated for efficacy. Ninety-eight episodes were major bleeds, 88 were minor bleeds, and 1 was not assessed.

One hundred and fifty-five bleeds (83%) were treated with a single infusion of Coagadex, 28 (15%) were treated with 2 infusions, 3 bleeds (2%) required 3 infusions, and 1 bleed (0.5%) required 4 infusions. Four bleeding episodes in 2 patients were considered treatment failures.

The mean dose of Coagadex per infusion was 25.4 IU/kg, and the mean total dose was 30.4 IU/kg. The recommended dose of 25 IU/kg to treat a bleed was maintained for 14 of the 16 patients. The other 2 patients used doses of up to 30 IU/kg and 33 IU/kg.

There were 176 adverse events in this trial, but only 6 events in 2 patients were considered possibly related to Coagadex. This included 2 reports of infusion site erythema in 1 patient, 2 reports of fatigue in 1 patient, 1 report of back pain, and 1 report of infusion site pain.

The second trial included patients who received Coagadex for perioperative management. Five patients received Coagadex for 7 surgical procedures.

For major surgeries, a median of 13 infusions (range, 2-15) and a median cumulative dose of 181 IU/kg (range, 45-210 IU/kg) were required to maintain hemostasis.

For minor surgeries, a median of 2.5 infusions (range, 1-4) and a median cumulative dose of 89 IU/kg (range, 51-127 IU/kg) were required to maintain hemostasis.

There were no adverse events related to Coagadex in this trial.

The company developing Coagadex, Bio Products Laboratory, received scientific advice on the design of the trials from the CHMP. Scientific advice is one of the agency’s main tools to facilitate and stimulate research and development within the EU.

Because factor X deficiency is rare, Coagadex was designated as an orphan medicine by the EMA’s Committee for Orphan Medicinal Products. Orphan designation gives pharmaceutical companies access to incentives that encourage the development of medicines for patients with rare diseases.

The CHMP’s recommendation to approve Coagadex for use in the EU is an intermediary step on Coagadex’s path to patient access. The CHMP’s opinion will now be sent to the European Commission for the adoption of a decision on an EU-wide marketing authorization.

Once a marketing authorization has been granted, decisions about price and reimbursement will take place at the level of each member state, taking into account the potential role/use of this medicine in the context of the national health system of that country.

EMA recommends therapy for bleeding disorder