Jumping the Gun on Advanced Medicines in Europe

Excitement overtook European patient organizations so completely in late March that they hailed a step forward in a rare treatment before the step had actually been taken. But their impatience and impetuosity are understandable given the slow emergence of advanced medicines in Europe – for which regulatory authorities and drug developers have both been repeatedly criticized in recent years. And as things turned out - the patient groups were not completely wrong.

On March 29, the European Medicines Agency announced that it had recommended granting a marketing authorization in the European Union for a genetically modified product for transfusion-dependent beta-thalassaemia (TDT): Zynteglo, from bluebird bio.  "Patients who depend on blood transfusions to manage beta-thalassaemia have an unmet medical need for new treatments," said the agency, and "Zynteglo is a new therapeutic option for patients for whom a related donor for stem cell transplantation is not available."

Good news for patients - just not quite as good as they thought.  Four days earlier, two patient organizations announced that EMA had approved bluebird bio’s application. And they quoted Dr. Chris Sotirelis, a patient expert at EMA, as saying: “The approval of Zynteglo is a breakthrough that offers a unique treatment choice to patients, as the first one-time gene therapy that addresses the underlying genetic cause of transfusion-dependent β-thalassaemia."

The patients were not only premature with their announcement - they were also inaccurate.  "As a result of this marketing authorization, Zynteglo™ is now approved for use in all European countries covered by the European Medicines Agency," they said.

But Zynteglo is not yet approved. It is not EMA's role to approve medicines. It makes recommendations on approvals based on reviews by its scientific committees (and it certainly recommended approval for Zynteglo.) It is the European Commission that issues the approval. In most cases, the Commission follows the advice of the agency – but it is not at all automatic - so this is not a pedantic distinction.

That was evident to bluebird bio, too, which itself issued a statement immediately after the patient organizations' claim appeared, aiming to correct the misinformation. Citing "a third-party press release", the company said " no opinion has been issued" by the EMA's scientific committee - the Committee on Human Medicinal Products. The product "is scheduled to be reviewed as part of the CHMP meeting from March 25 – 28,” it spelt out carefully.  And "if the CHMP’s opinion is issued it would then be reviewed by the European Commission, which has the authority to grant approval.”

The EMA announcement, when it came, was also careful to spell out the steps. "Because Zynteglo is an advanced therapy medicinal product, it  was assessed  by the Committee for Advanced Therapies (CAT) , the Agency's expert committee for cell- and gene-based medicines,” said EMA. "On the basis of the CAT’s assessment and positive opinion, EMA’s committee for human medicines  (CHMP) recommended a conditional approval for this medicine."

"The opinion adopted by the CHMP is an intermediary step on Zynteglo’s path to patient access," EMA went on. "The opinion will now be sent to the European Commission for the adoption of a decision on an EU-wide marketing authorization. Once the marketing authorisation has been granted, decisions about price and reimbursement will take place at the level of each member state, taking into account the potential role/use of this medicine in the context of the national health system of that country."

EMA did not add "Got it now?" to its statement.

The final act in this little drama, was a further statement from bluebird bio following the EMA announcement, and setting out its own view of the next steps. "A final decision by the European Commission for Zynteglo is anticipated in the second quarter of 2019," it said. The statement also quoted Dr. Androulla Eleftheriou, Thalassaemia International Federation Executive Director, remarking (aptly enough in the circumstances) "it is with great anticipation and eagerness that the international patient community has closely followed the dynamic rejuvenation of scientific interest and research of gene therapy in TDT over the last few years”.  In any event, the confusion should not be allowed to obscure the important step towards a new treatment that this decision represents. Patients may be less concerned about the legal niceties than about the prospect of filling an unmet need.

Peter O'Donnell is a freelance journalist who specializes in European health affairs and is based in Brussels, Belgium