Calvaroso (Aisf): “Dedicated regulatory pathway for drugs”

The revocation by the European Commission, on the advice of the EMA, of a therapy such as obeticholic acid for patients with primary biliary cholangitis “simply on the basis of data from a trial” affected by statistical problems “shows the real problem on the regulatory path of drugs for this” and, in general, for all “rare diseases where there is a risk of making the same mistake”. The authorization for the use “of a drug for a rare disease must have another path”, taking into account “real world data”. Vincenza Calvaruso, national secretary of Aisf, Italian Association for the study of the liver, said this morning while participating in a meeting with the press organized by Omar, Observatory of rare diseases, in collaboration with Amaf Aps Ets – Association of autoimmune diseases of the liver and Association EpaC Ets and with the unconditional contribution of Advanz Pharma, close to the World Cbp Awareness Day, which was celebrated on September 8.

In rare diseases “it is difficult to do trials similar to those for high prevalence diseases – continues Calvaruso – We cannot ask for exactly the same path and the same times. The “regulatory” path of a drug for a rare disease must take into account other information because it is difficult to do long-term enrollment in registration trials and it is difficult to imagine extremely long trials of 5-6 years as, in this case, for Cobalt. The arrival on the market of a drug that has already passed the registration phase – such as obeticholic acid in the Cobalt study – leads the clinician and patients to not be able to accept the possibility of being in a placebo group: it is also difficult from an ethical point of view”. It must also be considered that “enrollment, in the case of rare diseases, is complex precisely because of the number of patients, which is not very high”.

It is paradoxical, the expert points out, “that a drug can be revoked in terms of marketability on the basis of a trial, Cobalt in fact, which had a series of biases. And this problem – she specifies – can also manifest itself for other rare diseases, slowing down research and investment by companies. For this reason, in general, real world data must be included in the protocol for the registration of drugs for rare diseases. The data from these studies show what Cobalt failed to demonstrate. These are clinical data to be considered, especially in the decision to revoke a second-line drug, especially in the absence of an alternative. Everything must be adequately regulated because there is a risk that patients will be left without treatment. This has an impact on all rare diseases. We need – she concludes – a change at the regulatory level”.