Don’t put the kibosh on innovation

It’s very far from being a potential blockbuster, but for those few people afflicted by the inherited disorder for which it tailored, it is a wonder drug.

Glybera is a treatment for lipoprotein lipase deficiency, an ultra-rare condition in which patients lack an enzyme that is essential for breaking down fat. As a result, tiny fat globules accumulate in the pancreas, causing swelling and - painful – recurrent attacks of pancreatitis. 

There are estimated to be 4,000 people with the disorder worldwide. Overall, the 27 sufferers that have taken part in clinical trials had fewer acute attacks of pancreatitis after receiving Glybera. 

But sadly the treatment – developed at great expense over 14 years by the Dutch gene therapy specialist Amsterdam Molecular Therapeutics – was last week turned down for the third time by the European Medicines Agency (EMA).

This is not because of any concerns over the safety of using a virus to deliver a correct copy of the aberrant gene, but because EMA’s Committee for Medicinal Products for Human Use (CHMP) ruled the small number of patients who took part in trials means there is not sufficient evidence to demonstrate Glybera is effective.

EMA experts recommended Glybera approval

The CHMP reached this conclusion despite the fact that two other EMA expert bodies, the Committee for Advanced Therapies (CAT), which was set up specifically to provide guidance to the CHMP on gene therapies, and EMA’s Scientific Advisory Group, which advises on the science and biology behind novel products, both recommended Glybera be approved.

What’s more, the CHMP was considering Glybera for the third time because in January the European Commission made an unprecedented move, refusing to put its usual rubber stamp on the CHMP’s earlier recommendation that the product should be refused, and instructing the Committee to think again.

Lack of transparency

Yet more egregiously still, the CHMP itself voted 16 – 15 in favour of approving Glybera at its meeting last week. Unfortunately, for a product to get the nod it needs an absolute majority – or 17 votes – from all the members of the 32-strong committee, not just members who are present to vote. Members who are not present cannot vote in absentia.

For Jörn Aldag, CEO of Amsterdam Molecular Therapeutics (AMT), the lack of transparency is unacceptable. The rules need to be made clear because otherwise people just won’t make the investment, he says. AMT itself is now in liquidation, the assets have been transferred to a new company uniQure BV, and there will be no further investment in Glybera.

Bureaucracy gone bonkers

As Alastair Kent, one of Europe’s leading advocates for people affected by genetic disorders put it, "this is bureaucracy gone bonkers". 

The CHMP is not only flying in the face of the policy of the European Commission, it is also acting against the express wishes of the European Parliament and the impetus that the European Union’s health directorate DG Sanco is putting behind the development of new treatments for rare diseases.

For Kent, who is Director of Genetic Alliance, a body representing 150 UK patient organisations, and a former member of CAT, the Glybera decision has even wider implications "Frankly, it’s discriminatory to those affected by rare diseases to set the evidence bar at an impossible height, and demand standards of proof it is impossible to provide," he told Science|Business.

The ripples could go further, to halt development of personalized medicines, Kent believes. "When you put common diseases into subsets, you can’t go down the traditional, controlled-trials approvals route," he said.

Kiboshing innovation

The Glybera controversy is also a test for the recently installed head of EMA, Guido Rasi, who has pledged greater transparency in the way the Agency operates. To date this has consisted of flooding EMA’s website with thousands of pages of documents, creating a data deluge with the potential to cause greater obfuscation. 

How the EMA explains its decision on Glybera will be a far better measure of improvements in transparency.

This is critically important, because the end result of the lack of transparency and clarity in EMA’s rules and procedures will be to "kibosh innovation" Kent says. The people who are losing out are researchers, the industry, and most importantly the patients who are left with potentially avoidable ill health, he says.