For eight years, the biopharmaceutical company has been fighting in court to testify to the interference and imbalance of power within the European Medicines Agency.
2016. After years of hard work and research, PharmaMar, a Spanish company dedicated to the development and sale of medicines of marine origin for the treatment of cancer, is ready to release a revolutionary new drug, plitidepsin, capable of helping, and greatly, patients suffering from multiple myeloma. Yet, against all odds, the European Medicines Agency (EMA) refuses to authorize its marketing. After nearly two years of trying to amend the agency, PharmaMar is appealing that opinion to the European Union’s General Court. The ruling came in 2020 and gives reason to the company, but again there is a strange inversion of the situation: Germany, Estonia and the Netherlands are attractive. What is happening in the European biopharmaceutical sector? Are there hidden interests in the decisions of the exponential union? PharmaMar’s president, José María Fernández Sousa-Faro, tells us how the company lived through this legal saga.
An 8-year ongoing dispute, how did you experience it within the company?
We lived it with the conviction that we did what we had to do despite the lengthy procedures. Developing a pharmaceutical compound is a massive effort that, in this case, involved a team of more than 100 people for about ten years. When a drug, after completing all required studies, shows such positive results in patients that its approval is recommended by the two intervention countries designated by EMA, and that it is also approved in Australia, the feeling from PharmaMar is frustration. We are not aware of any other case that resulted in a rejection when both EMAs involved decided the product was acceptable.
The case also assumed a crisis of confidence in the exponential moving average and the balance of power within it. When did you first begin to suspect ulterior motives in refusing a license for plitidepsin?
The refusal of consent was completely unexpected. The position of the chair of the Committee for Medicinal Products for Human Use (CHMP) of EMA, Sweden’s Thomas Salmonsson, was so bold and incorrect that we suspected something strange from the first moment. They did not respect the time or the format, they falsified the date of issue of the document, the protocols for conducting the analysis and we found a clear disparity in comparison, in addition to many other flaws. This encouraged us to take EMA to court in Luxembourg.
What role did the massive weight of Sweden play within the agency?
Sweden is the country that has had the most weight in the EMA’s decisions since its inception. Thomas Salmonson has held various positions at EMA’s CHMP for about 19 years, as have many of his colleagues such as Jonas Bergh, also Swede, who also served for 19 years on the agency’s scientific advisory board and which, surprisingly, is an unpaid position. Is it altruistic? There is an indisputable element: Sweden is the country that has most often participated or participated in the evaluation dossiers of oncology drugs for human use, long before countries of more than 60 million people like France, Germany, the United Kingdom and Italy.
In 2020, the court agreed with you… What do you think would have prompted Germany, Estonia and the Netherlands to appeal the CJEU?
The Luxembourg court agreed with us and charged EMA with a conflict of interest with the Swedish pharmaceutical company “XNK Therapeutics AB” which was developing the drug “CellProtect” for the same disease, multiple myeloma. An appeal in cassation against this decision could have been lodged by the European Commission, on which the EMA relied, but it did not; I accepted the verdict. To everyone’s surprise, Estonia, Germany, and then the Netherlands appealed. Surprisingly, unlike Germany and the Netherlands, Estonia abstained in the vote that ended in a refusal to approve plitidepsin, suggesting that it was more of a political decision than a technical one. This makes us wonder: What did Estonia lose by refusing to obtain an approved drug for this disease? What happened between Estonia and the EMA? These facts contradict the approval we received in 2018 in Australia, where patients have another additional alternative for this incurable disease.
This aspect is perhaps the most troubling of the present case, because many European patients with multiple myeloma may have resorted to plitidepsin during these years…
Additional medication for multiple myeloma should always be welcomed. Moreover, a study was published of Australian patients who were given plitidepsin as an ‘end of life’ treatment showing its efficacy. On the other hand, the fact that it was not approved in Europe hindered its development as an antiviral drug against Covid-19, as we had to start development from the beginning, which made us arrive too late. And this is despite the fact that Science magazine published in 2022 that it is the most powerful antiviral against disease.
In Australia, it was approved in 2020. Did that somehow offset the effort invested?
Absolutely not, the damage is irreparable. The investment and risk assumed to develop a drug is only compensated if one envisages marketing it on a global scale. PharmaMar is a global company dedicated to achieving the maximum benefit for patients around the world. It is sad that Europe puts up so many obstacles, especially for European companies that offer innovative products. The worrying thing is that this has also happened to us with one of our NSCLC drugs. In the United States, we have received conditional approval from the Food and Drug Administration, as well as from other agencies including Switzerland, Canada and Australia. But here, the EMA asked us to do an additional study so we can provide it. Therefore, we must analyze what is happening in Europe with the agency.
and now? What will happen when the CJEU decision is issued?
We are awaiting the court’s decision on the appeal. If it is not in our favor, there is still a possible battle and we will not give up. We will proceed on the other four points of the complaint which have as strong an argument as those indicating a conflict of interest on the part of the EMA namely: violation of the principle of good governance, violation of the principle of equal treatment, and failure to comply with the obligation to state reasons, given that EU institutions are obliged to give reasons To adopt its decisions, violating the right of defense.
If we could go back to 2018, would you relive this whole process?
Without a doubt. We will act in the same way again, but more firmly, because now we know a lot more about how exponential moving averages work. For example, it does not have an independent compliance department, unlike the Food and Drug Administration in the United States. Today we also know of an incredible case of a product for multiple myeloma, thus the same indication of plitidepsin, which was curiously approved for a Swedish company, Oncopeptides, by the EMA but withdrew from the market by the Food and Drug Administration after warning of an increased risk of death from taking this drug.