Regulatory Transparency Needed
The EMA’s ultimate rejection of Glybera occurred at the end of a long, uncertain regulatory path. AMT initially filed Glybera in December 2009. In May 2010, it received a list of questions from EMA. After two meetings with the agency, in July 2010, the company stated that it would not be required to conduct more clinical trials and in November 2010, submitted its response to the EMA’s questions.
The agency then sent another list of questions to AMT, but Aldag maintained that the company’s interactions with the EMA continued to be positive and that they were looking forward to a decision in mid-2011. That decision, unfortunately for AMT, was one of nonapprovability.
Aldag told GEN, “I remain in a bit of a fog because of the contradictions in the process. Two rapporteurs, the Scientific Advisory Group (SAG) invited by the Committee of Advanced Therapies (CAT), as well as the CAT itself, said Glybera should be approved under exceptional circumstances.
“It beats me why the CHMP would overrule the CAT, which was installed by the European Union at taxpayers’ expense to specifically review new therapies such as gene and stem cell therapies.”
One of the reasons CHMP cited for its decision was that too few patients were enrolled in the trial for sufficient long-term data to be established. But approval under exceptional circumstances may be granted if for reasons of the orphan or ultra-orphan nature of the disease there will never be sufficient patients for a controlled trial to give conclusive evidence of clinical benefit, Aldag explained.
“All these expert groups had concluded that there are early signs of clinical benefit to patients, but the CHMP took a different position.” SAG and CAT concluded that data from three Glybera clinical trials demonstrated meaningful evidence of clinical efficacy without any major safety concerns. CHMP, on the other hand, concluded that AMT’s studies had not shown a consistent long-lasting benefit of Glybera in terms of lowering blood fats in a clinically relevant manner and reducing the rate of pancreatitis.
In the wake of CHMP’s recommendation, AMT cut its workforce from 88 to about 50 employees. Aldag told analysts on October 25 during a call, “We have no more money to invest in a nontransparent process, and we have no idea how to gain European approval for Glybera.”
The company’s pipeline currently includes AAV-based gene therapy products for hemophilia B, DMD, acute intermittent porphyria, and Parkinson disease at different stages of R&D. Clinical trials are funded through a combination of private financing and academic institutions.
AMT expects to hold meetings with FDA and Canadian regulatory authorities in mid-November to obtain views on Glybera and gene therapy in general. If the regulatory agencies are positive about the drug, project funding will be sought to support filing of marketing authorizations in North America in the second half of 2012, Aldag told analysts in October.