EMA Recommends Granting a Conditional Marketing Authorisation for Vintafolide for the Treatment of Platinum-resistant Ovarian Cancer that Expresses the Folate Receptor

Folate receptor status should be assessed by a diagnostic medicinal product approved for selection of patients for the treatment with vintafolide

On 20 March 2014, the European Medicines Agency Committee for Medicinal Products for Human Use (CHMP) recommended granting a marketing authorisation for vintafolide (Vynfinit) for the treatment of patients with a sub-type of platinum-resistant ovarian cancer for which there are limited approved treatment options. The CHMP has recommended approval for vintafolide together with the approval of two companion diagnostic medicines, etarfolatide (Folcepri) and folic acid (Neocepri) that will help identify patients who may benefit from treatment with vintafolide. All three of these medicines have an orphan designation and were recommended for conditional marketing authorisations.

A conditional marketing authorisation is granted to a medicinal product that fulfils an unmet medical need when the benefit to public health of immediate availability outweighs the risk inherent in the fact that additional data are still required. The marketing authorisation holder is likely to provide comprehensive clinical data at a later stage.

Vintafolide

The CHMP adopted a positive opinion, recommending the granting of a conditional marketing authorisation for the treatment of adult patients with platinum-resistant ovarian cancer that express the folate receptor on all target lesions. Folate receptor status should be assessed by a diagnostic medicinal product approved for the selection of adult patients for treatment with vintafolide, such as etarfolatide.

Vintafolide was designated an orphan medicinal product on 9 February 2012. The applicant for this medicinal product is Endocyte Europe, B.V.

Vintafolide is to be available as a 2.5 mg powder for solution for injection. The active substance in the drug is vintafolide, which belongs to the therapeutic group of vinca alkaloid and analogues. Vintafolide consists of folic acid and the cytotoxic agent desacetylvinblastine hydrazide (DAVLBH). The folic acid component enables DAVLBH to be delivered preferentially to cancer cells expressing folate receptors. Once delivered inside cancer cells, DAVLBH is released from vintafolide and acts by inhibiting microtubule assembly and arresting cells in mitosis.

The benefits with vintafolide are its ability, in combination with pegylated liposomal doxorubicin (PLD), to improve progression-free survival in patients with platinum-resistant ovarian cancer when compared with treatment with PLD alone.

The most common side effects are fatigue, stomatitis, neutropenia, anaemia, nausea, palmar-plantar erythrodysaesthesia, constipation, rash and peripheral sensory neuropathy.

A pharmacovigilance plan for vintafolide will be implemented as part of the marketing authorisation.

The text for the approved indication is as follows: "Vynfinit in combination with pegylated liposomal doxorubicin (PLD) is indicated for the treatment of adult patients with platinum resistant ovarian cancer (PROC) who express the folate receptor (FR) on all target lesions. Folate receptor status should be assessed by a diagnostic medicinal product approved for the selection of adult patients for treatment with vintafolide, using single photon emission computed tomography (SPECT) imaging, in combination with Computed Tomography (CT) or Magnetic Resonance Imaging (MRI)".

Vintafolide is to be prescribed by physicians experienced in chemotherapy treatment.

Etarfolatide

On 20 March 2014, the CHMP adopted also a positive opinion, recommending the granting of a conditional marketing authorisation for intravenously administered folic acid, in single photon emission computed tomography (SPECT) imaging to select adult patients with ovarian cancer suitable for treatment with the anticancer medicine vintafolide.

Etarfolatide was designated an orphan medicinal product on 10 September 2012. The applicant for this medicinal product is Endocyte Europe, B.V.

Etarfolatide is to be available as a 100 microgram kit for radiopharmaceutical preparation. The active substance consists of folic acid and a technetium-99m chelating peptide. It binds to the folate receptor expressed on the surface of many types of cancers, including ovarian cancer. Following radiolabeling with technetium-99m, etarfolatide is used in SPECT imaging to detect cancer cells with folate receptor.

The benefits with etarfolatide are its ability to detect adult patients with platinum-resistant ovarian cancer that express the folate receptor on all target lesions and who are therefore suitable for treatment with vintafolide, which targets cancer cells expressing the folate receptor. The only side effect reported with etarfolatide was pruritus, which was reported uncommonly. A pharmacovigilance plan for etarfolatide  will be implemented as part of the marketing authorisation. The text for the approved indication is as follows: "This medicinal product is for diagnostic use only. After radiolabelling with sodium pertechnetate (99mTc) solution, Folcepri is indicated, after intravenously administered folic acid, for single photon emission computed tomography (SPECT) imaging, in combination with Computed Tomography (CT) or Magnetic Resonance Imaging (MRI), for the selection of adult patients for treatment with vintafolide, a folate receptor (FR) targeted therapeutic for use in ovarian cancer”.

Etarfolatide is to be prescribed by physicians experienced in radioisotope diagnostic imaging.

Folic acid

On 20 March 2014, the CHMP adopted also a positive opinion, recommending the granting of a conditional marketing authorisation for the medicinal product folic acid (Neocepri) to be used in patients with ovarian cancer to enhance the image quality of 99mTc-etarfolatide single photon emission computed tomography (SPECT).

Neocepri was designated an orphan medicinal product on 10 September 2012. The applicant for this medicinal product is Endocyte Europe, B.V.

Neocepri is to be available as a 1 mg/ml solution for injection. The active substance of Neocepri is folic acid to be administered intravenously prior 99mTc-etarfolatide SPECT imaging.

The benefits with Neocepri are its ability to reduce the background (i.e. non-specific) activity observed on SPECT imaging in most normal, non-target tissues including in the intestines, liver, kidney, and spleen, thereby improving the image quality of the scans.

A pharmacovigilance plan for Neocepri will be implemented as part of the marketing authorisation.

The text of the approved indication is as follows: "This medicinal product is for diagnostic use only. Neocepri is administered prior to 99mTc-etarfolatide, a folate receptor (FR) targeted radiodiagnostic imaging agent for use in ovarian cancer. Neocepri is indicated for the enhancement of 99mTc-etarfolatide single photon emission computed tomography (SPECT) image quality.”
Detailed recommendations for the use of all three products will be described in the summary of product characteristics, which will be published in the European public assessment reports and made available in all official European Union languages after the marketing authorisation has been granted by the European Commission.