Eisai ‘outraged’ by decision on epilepsy drug

A ruling in Germany which has found Eisai’s epilepsy drug Fycompa to have no extra benefits to existing treatments has been heavily criticised by the company and leading specialists.

The company says it is ‘outraged’ at the decision, as it appears to pay no heed to data from open-label studies of thousands of people with epilepsy in Germany who have benefited from the drug.

Germany’s IQWiG (Institute for Quality and Efficiency in Health Care) is the country’s health technology appraisal authority, and works hand-in-hand with another body, the Federal Joint Committee (G-BA) to decide which treatments are recommended for use.

IQWiG’s role is similar to the UK’s NICE – and that includes its ability to cause controversy among pharmaceutical companies and others with its decisions.

Eisai is just the latest pharma company to object to what they see as IQWiG’s simplistic approach to appraising the clinical and cost effectiveness of new drugs.

IQWIG applies a strict rule that clinical trial data for a new drug must compare it no more than three standard comparator drugs. Trials of Fycompa (perampanel) fell foul of this rule because it was compared to more than three therapies – but Eisai says the regulator’s rule is entirely inappropriate in epilepsy.

IQWiG’s rule doesn’t acknowledge that combination or adjunctive therapy is integral to many therapy areas, such as cancer, multiple sclerosis and epilepsy. In epilepsy, two or three additional treatments are routinely used – so called ‘rational polytherapy‘ in order to control the condition when it becomes refractory, or non-responsive to monotherapy.

Fycompa (perampanel) is an adjunctive therapy, and can be used in combination with more than 20 standard therapies currently in use. These drugs have a range of different modes of action, which allow doctors to try out different combinations to control a range of symptoms in patients.

Eisai’s drug is licensed to treat partial onset seizures – these are less severe than a ‘generalised seizure’ but nonetheless very debilitating and unpredictable. Up to a third of people with epilepsy do not achieve seizure freedom despite appropriate therapy with anti-epileptic drugs (AEDs).

IQWiG says Eisai has deviated from the appropriate comparative therapy as defined by the G-BA. Eisai says IQWiG’s assessment carries no comment on the drug’s proven clinical efficacy and safety, demonstrated by studies via which it gained EU approval in September 2012.

“IQWiG has yet again failed to acknowledge the benefit of Fycompa based purely on methodological, rather than clinical, considerations” said Gary Hendler, president & chief executive of Eisai EMEA.

“Patients are our first concern and we feel that this new report has again ignored the over 4,000 people with epilepsy in Germany who have already benefitted from Fycompa.”

Hendler concluded that the company was confident that the G-BA would take a broader perspective and recognised that “additional adjunctive treatment options for people with epilepsy are always needed.”

Professor Heinz Beck, president of the German Society of Epileptology (DGfE) added his voice to concerns about the ruling.

“It is becoming more and more recognised that treatments in epilepsy have to be individually tailored. Even though we do not understand how to predict who will benefit from a given medication, access to the full complement of new medicines that may help is of crucial importance for the future. This is particularly relevant given the relatively high percentage of people that remain refractory to treatment.

He concluded: “It is worrying that IQWiG do not recognise this aspect, which is particularly relevant for etiologically complex CNS diseases, in particular epilepsy.”

Eisai says that in addition to its standard clinical studies, it has much real world data on the drug’s efficacy and safety of adjunctive perampanel in the treatment of partial onset seizures.

A multi-centre, six-month observational study from nine epilepsy centres in Germany and Austria found that half of the 281 people with highly refractory epilepsy who took part in the study experienced at least a 50 per cent reduction in seizure frequency, and up to 15 per cent became seizure free with adjunctive perampanel.

Fycompa is a first-in-class drug selectively targeting AMPA receptors, which play a critical role in causing seizures. First launched in 2012, the company had hoped the drug would reach global sales of $1 billion within three years, but it is unlikely to reach this target within this timeframe.

GlaxoSmithKline’s (GSK) Trobalt (retigabine) is a rival adjunctive therapy launched in 2012, but it has struggled to make inroads into the market. IQWiG’s response in Germany has played a part in this – the regulator raised the same comparator-related objection to GSK’s drug. It then recommended the drug be included in a reference-pricing system which would have seen a price similar to generic drugs imposed on it.

The company was so incensed by the decision that it withdrew the drug entirely from the German market.

GSK was not the first company to make such a drastic move – it followed two others, Pfizer’s Xiapex and Novartis’ Rasilamlo. In addition, Boehringer Ingelheim decided not to launch its type 2 diabetes drug Trajenta in the country at all because of similar disagreement on the appropriate comparator.

The G-BA has the final say on the cost-effectiveness decisions, and is expected to make its decision on Fycompa by November 2014.

The process now enters a ‘question and answer’ consultation period in which IQWiG accepts written statements and holds oral hearings. Eisai says it is confident that the G-BA will make a “more flexible, patient-oriented approach to their decision making process” which it hopes will consider evidence of Fycompa’s clinical benefit and the needs of people with poorly controlled epilepsy.

However without changes to IQWiG’s comparator rule, it is certain that further clashes will occur over new drug launches in Germany.

Links

Embracing real-world evidence is driving a new world for pharma

Anti-epileptic drugs – the problem with switching

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