The European Medicines Agency (EMA) has recommended the refusal of the marketing authorisation for tagraxofusp (Elzonris), a medicine intended for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN). The Agency issued its opinion on 23 July 2020.

The company that applied for authorisation, Stemline Therapeutics B.V, may ask for re-examination of the opinion within 15 days of receiving the opinion.

Elzonris was developed as a medicine for treating adults with BPDCN, a rare and aggressive type of acute myeloid leukaemia. In BPDCN, the bone marrow produces large numbers of immature white blood cells called plasmacytoid dendritic cells. These build up in the bone marrow, taking the place of normal blood cells, and spread to the skin: most patients develop non-itchy damaged areas, which often look like bruises or nodules. The disease may also cause enlargement of the spleen or liver and a reduction of the number of circulating blood cells.

There is no approved treatment for BPDCN in the EU.

Elzonris contains the active substance tagraxofusp and was to be available as an infusion given into a vein.

Elzonris was designated an orphan medicine (a medicine used in rare diseases) on 11 November 2015 for the treatment of BPDCN.

The active substance in Elzonris, tagraxofusp, is made up of a diphtheria toxin, which has been linked to interleukin-3. The interleukin-3 attaches to receptors, which are found at high levels on the surface of BPDCN cancer cells. Once attached to cancer cells, it is taken up by them, allowing the toxin to be released inside and kill them. This is expected to prevent cancer spread and reduce symptoms of the disease.

To support its application, the company presented results from a single small study involving 47 adults with BPDCN that could not be treated in other ways. The main measure of effectiveness which was recorded in a group of 13 first line patients was the number of patients without any signs of disease after treatment or with just minimal skin damage remaining.

The Agency was concerned that due to the design of the study and the small number of patients involved, it was not possible to be sure how effective the medicine was in treating BPCDN. In addition, the medicine could cause capillary leak syndrome (an unpredictable, potentially life-threatening side effect due to increased permeability of small blood vessels), which had led to some fatal outcomes.

Therefore, the Agency’s opinion was that the benefits of Elzonris did not outweigh its risks and it recommended refusing marketing authorisation.

The company informed the Agency that there are no consequences for patients in clinical trials or in compassionate use programmes with Elzonris.