Enpaxiq: Withdrawal of the marketing authorisation application

Enpaxiq is a medicine that contains the active substance pacritinib. It was to be available as capsules to be taken by mouth.

Enpaxiq was expected to be used to treat patients with an enlarged spleen or other symptoms of myelofibrosis – a disorder in which scar tissue builds up in the bone marrow where blood cells are produced.

Enpaxiq was designated an 'orphan medicine' (a medicine to be used in rare diseases) on 25 August 2010 for different types of myelofibrosis.

The active substance in Enpaxiq, pacritinib, blocks the action of JAK2 and FLT3, two proteins involved in the production and growth of blood cells. In myelofibrosis, patients have too much of these proteins, which cause the production of immature blood cells, some of which migrate to organs such as the spleen, causing them to become enlarged. By blocking these proteins, Enpaxiq is expected to slow down the production of immature blood cells and thereby help reduce the symptoms of the disease.

The company presented data from a main study in 327 patients with myelofibrosis that looked at the number of patients whose spleen size reduced by at least 35% after 24 weeks of treatment. The study compared Enpaxiq with 'best available therapy', which included treatments that do not act on JAK proteins such as hydroxyurea or supportive care.

The application was withdrawn after the CHMP had evaluated the initial documentation provided by the company and formulated a list of questions. The company had not yet responded to the questions at the time of the withdrawal.

At the time of the withdrawal of application, the CHMP was of the provisional opinion that Enpaxiq could not have been approved for myelofibrosis.

The Committee had a number of concerns: the reduction in spleen size, the main measure of effectiveness in the study, appeared to be lower with Enpaxiq than with another medicine of its class, with no improvement in symptom scores; the incidence of low blood platelet levels (which can cause bleeding) was higher in patients treated with Enpaxiq; and a higher number of deaths occurred in patients taking Enpaxiq than in those receiving best available therapy, including deaths due to bleeding and effects on the heart.

Furthermore, the CHMP noted that more information was needed about the starting materials used in the manufacture of Enpaxiq and how it acts on certain target proteins in the body.

Given these concerns, the Committee was of the opinion that the benefits of Enpaxiq had not been shown to outweigh its risks.

The company stated in its letter to the Agency that it was withdrawing the application because there was not enough time in the current application procedure to provide new data from a second main study with Enpaxiq. The company said that it intends to integrate the new data from the study into its current dossier before approaching EMA to discuss a new application.

The company informed the CHMP that there are no consequences for patients currently included in clinical trials or compassionate use programmes with Enpaxiq.

If you are in a clinical trial or compassionate use programme and need more information about your treatment, contact the doctor who is giving it to you.