Plitidepsin

Nearly eight years after PharmaMar first sought EU approval of its multiple myeloma (MM) drug Aplidin (plitidepsin) — and following back-to-back rejections by a drug advisory body for the European Medicines Agency (EMA) — the Spanish drugmaker has got a second wind. The European Commission (EC) ruled that during Aplidin’s initial review by the EMA’s Committee for Medicinal Products for Human Use (CHMP), one of the participants was involved in the development of a rival product. “Consequently, in order to avoid any doubt as to the objective impartiality of the assessment of the application, the Commission has decided it is appropriate to revoke the decision to refuse marketing authorisation for Aplidin,” PharmaMar said in a statement. The EMA will now review CHMP’s earlier regulatory opinions on Aplidin and reevaluate the candidate’s application “from the time of the onset of the detected procedural irregularity.” Legal sagaThe committee had first rejected PharmaMar’s application for Aplidin in late 2017 and again in early 2018, after which the company filed a lawsuit against the EC seeking the annulment of the regulator’s decision.PharmaMar was successful in its suit in October 2020, with the General Court of the EU ruling in favour of an annulment due to conflict of interest.

The European Commission (EC) has acknowledged that an expert from the Scientific Advisory Group, who was developing a rival product was allowed to participate in the Marketing Authorization procedure for Aplidin (plitidepsin). The EC requests the European Medicines Agency, EMA, to re-evaluate the application for Aplidin in Multiple Myeloma. This exceptional decision supports what PharmaMar has always maintained, namely that there was a conflict of interest among the EMA experts who evaluated the therapy. The Company will demand the reassessment process to be conducted with absolute impartiality, equality and transparency by the EMA. PharmaMar (MSE:PHM) has received a notification from the European Commission (EC) informing the Company of its decision to revoke the refusal to grant Marketing Authorization for Aplidin® in Multiple Myeloma. According to the communication received, the EC has re-evaluated the criteria applied for the participation of experts in the administrative procedure for the Marketing Authorization of Aplidin, as well as the relevant EMA rules governing conflicts of interest, so that they can ensure the objective impartiality of these experts. Therefore, the EC notes that one of the experts of the Scientific Advisory Group (SAG) involved in the development of a rival product, was allowed to participate in the Marketing Authorization procedure for Aplidin, in accordance with the EMA rules applicable at the time. Consequently, in order to avoid any doubt as to the objective impartiality of the assessment of the application, the Commission has decided it is appropriate to revoke the decision to refuse Marketing Authorization for Aplidin. It is also reported that the Commission has forwarded to the EMA the opinions of the Committee for Medicinal Products for Human Use (CHMP), to request the re-evaluation of the application from the time of the onset of the detected procedural irregularity. The European Commission's reversal of the decision, which is totally exceptional, is a de facto acknowledgement that PharmaMar did not have all the necessary guarantees in the evaluation process for Aplidin. Now that the registration dossier has been returned to the EMA, the Company will ensure that the procedure is conducted with absolute impartiality and on a level playing field. History of the lawsuit, 7 years of litigation PharmaMar filed a lawsuit in October 2018 before the General Court of the European Union against the EC, seeking the annulment of the Commission's Implementing Decision, by which it denied Marketing Authorization for Aplidin as a treatment for patients with Multiple Myeloma. The reason for the lawsuit related to the strict conflict-of-interest checks carried out by the experts appointed by the EMA and the correct analysis of the scientific evidence presented by PharmaMar. In October 2020, the General Court of the European Union upheld PharmaMar's claim in full, at the extreme end of the conflict of interest, annulling the European Commission's decision to refuse Marketing Authorization for Aplidin for the treatment of patients with Multiple Myeloma, and ordered the Commission to pay the costs. In 2021, Estonia and Germany appealed the decision to the EU Court of Justice, although the EC decided not to do it, which could be understood as implicitly accepting the ruling. In 2023, the Court of Justice of the European Union annulled the judgment of the General Court and referred the case back to the General Court, to rule again on the first ground for annulment urged by PharmaMar in its initial application, and to rule, if it considered it necessary, on the other claims for annulment in its action. That is, to rule not only on the conflict of interest and the breach of the Principle of Objective Impartiality by the EMA, but also on the breach of the Principle of Good Administration, the breach of the Principle of Equal Treatment and incorrect analysis of the scientific evidence presented by PharmaMar, the breach of the obligation to state reasons and the breach of the rights of defense. The Company has always maintained that, during the evaluation process of its drug, Aplidin for the treatment of Multiple Myeloma, there was a conflict of interest of several members based on numerous objective elements, including the cooperation of one of its members with a Swedish company, XNK Therapeutics AB, developing a rival drug, as well as its participation in the development of other competing drugs.