LONDON – Amsterdam Molecular Therapeutics (AMT) NV is now poised to begin the Phase III extension study of Glybera, its gene therapy treatment for lipoprotein lipase deficiency, and is paring back expenditure as it awaits a response from the European Medicines Agency (EMA) to its request for a re-examination of the Glybera file.
The financial position is so precarious that AMT executives have agreed to take part of their remuneration as shares to save money, while the company tries to nurse Glybera to the finish line.
Ten previously treated patients have agreed to take part in the Phase III extension, following the rejection of Glybera in the ultra-orphan indication by the EMA in June.
"This is almost the maximum we could achieve, and shows the commitment of patients treated in the past, in wanting to help get the drug approved," said Jörn Aldag, CEO.
He added that this also exceeds the number expected by the EMA in its request for more evidence that Glybera (aplipogene tiparvovec) remains effective over time. The trial will now restart next month. The EMA has indicated approval may be possible if the additional data from treated patients confirm the results in the original file by the end of 2011.
The aim of the Phase III extension is to provide further data, using chylomicron metabolism as a biomarker for increased lipoprotein lipase activity in patients lacking the gene that produces that protein. The trial will build further evidence that the breakdown of chylomicrons produced after eating is increased following a single treatment with Glybera, and that there is a subsequent reduction in the incidence of acute pancreatitis, which is the major clinical symptom of lipoprotein lipase deficiency.
Aldag noted that AMT had planned to collect the data as part of a postmarketing study. He expects the EMA to respond to the request to re-examine the file by November, he said during a conference call held to discuss the Amsterdam, the Netherlands-based company's half-year financial results.
AMT's finances are stretched to the limit, but the management team has demonstrated its collective faith in getting Glybera approved by taking "a significant, fixed proportion" of their salaries in the form of new AMT shares, and by making cash investments in the company.
As a result of that, and further moves to limit cash burn by cutting back on other programs and terminating a number of flexible staff working contracts, AMT will reduce overhead by 7 percent. However, there is no opportunity to cut back on the main item of expenditure, which is getting Glybera through to approval. AMT had cash of €9.1 million, (US$13.2 million) or six months' cash at the end of June, but said the economy measures will allow it to eke out resources into 2012.
The company is looking for a partnership deal for Glybera, or for its gene therapy for hemophilia B. The first patient in the ongoing trial in that program, taking place at St. Jude Children's Research Hospital in Memphis, Tenn., is still generating endogenous Factor IX, 18 months after being treated.
"This is our second gene therapy trial to show lasting benefit from a single treatment," Aldag said.
Earlier this month AMT began enrolling patients into a pre-observation study to provide baseline data for a subsequent gene therapy trial in acute intermittent porphyria. The program, in collaboration with the University of Navarra, of Spain, and the Spanish company Digna Biotech, won a European Union grant earlier this year, which is worth approximately €1 million to AMT. That covers the majority of the company's costs for the program, which is due to begin administering treatment in 2012.