AMT's gene therapy rebuffed as cash clock ticks

It was always possible that European approval for Glybera, Amsterdam Molecular Therapeutics’ novel gene therapy, would be refused, but the news is disheartening all the same. A regulatory win was desperately needed to reignite hopes for a field that has struggled to make much progress over the last few years (Event - AMT hoping to make history with gene therapy approval, May 10, 2011).

The set back is also a big disappointment for AMT, which needs to raise funds in the next 12 months; the company lost two-thirds of its market value today, declines exacerbated by its precarious financial position. Chief executive Jörn Aldag believes that Glybera, which treats the very rare genetic condition lipoprotein lipase deficiency (LPLD), could still be approved by the end of the year. With the cash clock ticking loudly AMT will struggle to survive any further setbacks.

Long term data

AMT believes that the European Medicines Agency’s decision reflects insufficient proof of the long term clinical benefit of Glybera. The therapy replaces a gene lacked by sufferers that codes for a crucial enzyme needed to break down fat in the bloodstream - administration involves a one-off series of 40 intramuscular injections over three hours. The gradual accumulation of fat causes the complications of LPLD: pancreatitis and cardiovascular problems.

So far the company has only submitted data from three patients using a particular test that the regulator believes is crucial to establish long term benefit of the therapy. Only 27 patients were treated with Glybera over the clinical programme, reflecting the rarity of a condition that only afflicts 1 or 2 people in a million.

Mr Aldag stresses that the regulator does not want to see more people enrolled in the trial. A further study with patients already treated with Glybera has already been planned, to confirm continuous efficacy, he says. The test will measure fat particles in the bloodstream following a meal, in patients treated with Glybera several months or years previously.

“We knew this data was needed. They’ve made something we thought we could do post approval, a pre-approval requirement,” he tells EP Vantage.

Endorsement

Data from a “few more” patients is required, which will be collected in the next couple months and sent to the regulator. Further evidence that Glybera reduces the risk of pancreatitis and the safety of the intramuscular administration technique will also be gathered. The re-examination procedure should conclude by the end of 2011.

Despite the desertion of investor confidence today, Mr Aldag believes this development represents a delay to approval, rather than anything more terminal.

“If you read the Q&A they sent us, it is very clear they are endorsing gene therapy. They did not recognise any safety risks that made them think gene therapy is not approvable,” he says. “This is why I think we’re not in a bad position because now it’s clear what they want.”

Assuming the new data confirms the long term efficacy seen in previously tested patients, and that AMT’s interpretation of the agency’s response is correct, Glybera could still make it to the market in Europe.

“I share their interpretation this is a potential delay. Adding a few more patients to the database could help,” says Jan Van den Bossche, analyst at Petercam. “The question is there is limited cash available. Even though you could say there is some possibility the negative opinion is reversed by the end of the year, the stakes are high because of the cash position.”

Cash position

AMT raised €14.3m in an equity fundraising last October, selling stock to existing and new shareholders at €1.70 a share. The stock closed at a record low of 61 cents this afternoon, giving the company a market value of €16.2m ($23m).

At the end of March, the company had €13.1m in the bank and over the last year has been burning approximately €4.5m a quarter. Assuming costs can be pared back, the company should be able to see out the year - Mr Aldag predicts the funds should last until early 2012.

It seems highly unlikely that investors – including loyal venture capital firms which first invested in AMT back in 2006 and still control almost a third of the stock – will be willing to stump up more cash until the European verdict is known. Events today demonstrated exactly why many other investors refuse to touch gene therapy.

The story is certainly not over for Glybera, but the next few months are crucial.

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