EMA refused the marketing authorisation for pralatrexate intended for the treatment of adult patients with peripheral T-cell lymphoma
Final outcome of re-examination of previously adopted negative opinion
- Date : 26 Apr 2012
- Topic : Anticancer agents & Biologic therapy
On 19 January 2012, the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) adopted a negative opinion, recommending the refusal of the marketing authorisation for the medicinal product pralatrexate (Folotyn), intended for the treatment of peripheral T-cell lymphoma. The company that applied for the authorisation is Allos Therapeutics Limited.
The applicant requested a re-examination of the CHMP opinion. After considering the grounds for this request, the CHMP re-examined the initial opinion, and confirmed the refusal of the marketing authorisation on 19 April 2012.
It is a medicine that contains the active substance pralatrexate. It was to be available as a solution for infusion. Pralatrexate was expected to be used to treat adults with peripheral T-cell lymphoma. It was designated an orphan medicine (a medicine to be used in rare diseases) on 13 April 2007 for the treatment of peripheral T-cell lymphoma.
Pralatrexate is an antimetabolite medicine. In the body, it is expected to take the place of folic acid and attach to an enzyme dihydrofolate reductase. By attaching to dihydrofolate reductase, pralatrexate is expected to block the enzyme’s activity, inhibiting the division of the cancer cells and eventually killing them.
What did the company present to support its application?
The effects of pralatrexate were first tested in experimental models before being studied in humans.
The company presented the results of one main study involving a total of 115 adults with peripheral T-cell lymphoma which kept coming back or did not respond to previous treatments. Patients were given pralatrexate together with vitamin B12 and folic acid supplements (to compensate for the deficiency in these vitamins that may occur during pralatrexate treatment). The main measure of effectiveness was based on the proportion of patients who responded to treatment. Response to treatment ranged from having improvements in the disease to having no sign of cancer. In this study, pralatrexate was not compared with any other treatment.
What were the CHMP’s main concerns that led to the refusal?
In January 2012, the CHMP was concerned that the main study was designed in a way that did not allow the Committee to assess the benefit of the medicine, particularly since pralatrexate was not compared with any other treatment or placebo in another group of patients. Moreover, there was no clear improvement seen in the condition of the patients, as the study looked at the patients’ response to treatment but did not further allow the Committee to assess the effect on overall survival or progression free survival. The CHMP was of the opinion that there was insufficient evidence to establish the benefits of pralatrexate in the treatment of peripheral T-cell lymphoma. Therefore, at that point in time, the CHMP was of the opinion that the benefits of pralatrexate did not outweigh its risks and recommended that it be refused marketing authorisation.
During the re-examination in April 2012, the CHMP’s concerns were not resolved. In particular, the Committee considered that the data submitted by the applicant were insufficient to establish the benefits of pralatrexate in the treatment of peripheral T-cell lymphoma. The CHMP therefore confirmed its initial negative opinion.
What consequences does this refusal have for patients in clinical trials or compassionate use programmes?
The company informed the CHMP that there are no consequences on patients currently included in clinical trials or compassionate use programmes with pralatrexate. If somebody is in a clinical trial or compassionate use programme and need more information about the treatment, they advised to contact the doctor who is administering pralatrexate.
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