Shire’s strong Vyvanse data and lack of abuse potential bode well for use in EU paediatrics – psychiatrists

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Shire’s (LON:SHP) Vyvanse for attention-deficit/hyperactivity disorder (ADHD) will be more beneficial compared to existing options for paediatric patients if approved in Europe, psychiatrists said.

Physicians interviewed support Vyvanse (lisdexamfetamine dimesylate; LDX) but said it could encounter issues getting approved in certain European countries due to a stigma that exists around some current ADHD treatments. However, the likely low abuse potential of the drug is expected to be a large advantage in the regulatory assessment of its risk-benefit profile, they added.

A European Marketing Authorisation Application (MAA) for once-daily LDX was accepted for review in January 2012 by the UK’s Medicines Healthcare products Regulatory Agency (MHRA), a Shire spokesperson said. The MAA process for LDX is currently ongoing, and Shire cannot speculate on the outcome or its timelines, the spokesperson added.

At this stage Shire has decided to only pursue approval for children and adolescents under 18, and from the data it has, it will likely gain an okay, said Dr Philip Asherson, professor, Molecular Psychiatry, Kings College London.

LDX is approved in the US and Canada and branded as Vyvanse. The US Food and Drug Administration first approved the drug in 2007 and Health Canada in 2009, both for children ages 6-12 years. Both authorities subsequently gave Vyvanse the nod for adolescents and adults.

Vyvanse made USD 805m in 2011 sales, according to Shire’s 2011 Annual Report, and analysts have forecasted it could reach global sales of up to USD 2bn by 2018.

ADHD is a behavioural disorder that usually starts in early childhood, according to the UK’s National Institute for Health and Clinical Excellence. Frequently occurring symptoms include inattentiveness, disorganisation, impulsiveness and hyperactivity. The condition can impact coordination, sleep and mood and in turn affect a child’s learning, social interaction and personal development, among other things.

Chances in the EU

The MHRA has agreed to act as the Reference Member State for the decentralised procedure (DCP), which will initially include eight European countries, according to a January press release.

An investigator on the European trials said physicians and patients are waiting for this drug to become available. Long-acting formulations such as LDX provide 14 hours of efficacy, which is the best option for patients, the investigator added, noting this is specifically appealing to the adult population. Currently there are no drugs approved for adults with ADHD in the EU.

There is no doubt that the efficacy data for LDX is robust, and from clinical trials, it appears to be the best drug we have, said Dr Hervé Caci, Hôpitaux Pédiatriques de Nice Chu-Lenval, France. It looks like it may be more effective than previously approved drugs, he added.

There are some biases in the data, which cannot be ignored, for example, in the comparison trials, the doses that were compared against each other may have been favourable to LDX, said Caci, an investigator on the Phase III European studies. This does not matter, as it is likely to be acceptable to regulators anyway, he added.

An EU-based psychiatrist familiar with the drug said there is still a lot of unpublished EU trial data he is aware of; however, there was nothing that was yet to be released that could negatively affect the situation.

There is still a need for different options to what is already available in Europe, noted one UK-based ADHD expert. However, it is yet to be seen whether LDX can harness a similar level of popularity as it has seen in the US, the expert added.

The majority of ADHD medications currently available in Europe contain immediate- or modified-release methylphenidates, which belong to the stimulant class of medication, the spokesperson said. A long-acting nonstimulant, atomoxetine, is also available, the spokesperson added.

Approved ADHD drugs for children and adolescents in Europe include Novartis’ (VTX:NOVN) Ritalin (methylphenidate), Johnson & Johnson’s (NYSE:JNJ) Concerta (methylphenidate) and Eli Lilly’s (NYSE:LLY) Strattera (atomoxetine).

One important consideration that has the potential to derail LDX’s debut into Europe is that there could be a potential issue with agreement from all the countries involved in the DCP, the UK-based expert noted. Though the initial opinion from the UK’s MHRA may be positive, if a decision is negative in the second-round countries it could impact earlier positive decisions, the expert explained.

Abuse potential

The registration process will initially not include France, said Caci. There are a lot of reservations about ADHD treatments specifically in France, he explained. Abuse potential is a major issue specifically because of known abuse of already-approved ADHD drugs such as Ritalin by heroin or cocaine addicts, he said.

The first investigator noted one of the main benefits it is hoped that LDX will bring is that it may not have an abuse potential associated with it. The fact that abuse potential is associated with these drugs is a big issue in their acceptance, the investigator added.

LDX’s active therapeutic ingredient is only metabolised after it has been absorbed intact in the small intestines, said Dr Micheal Banov, medical director, Norwest Behavioral Medicine, Georgia, US. This means it should not be able to be crushed and snorted or injected like the other stimulants that are available for ADHD, he explained.

LDX is the most successful ADHD drug in Canada, said Dr Roger McIntyre, head, Mood Disorders Psychopharmacology Unit, University of Toronto. “[LDX] is a very reliable drug that provides robust efficacy with a very predictable benefit within the first few days of treatment,” he added. This drug is extremely safe because of the lack of risk of abuse, he said.

The question is whether Shire can successfully make its case to regulators that this is indeed the case, McIntyre added.

“Patients with true ADHD do not generally get high on stimulants,” said Dr Mike Henry, medical director, Department of Psychiatry, Massachusetts General Hospital, US. Rather, ADHD patients often find that stimulants calm their mood and aid concentration and allow them to work more productively, he explained. Some patients might become dependent on these effects and become attached to the level of productivity the drug gives them, Henry added.

The potential of misuse of LDX should be low as long as it is prescribed responsibly, Henry noted.

Shire takes the potential misuse, abuse and diversion of its drugs seriously and has a comprehensive Risk Management Program and various disease state educational and support activities in place, the spokesperson said.

Shire’s market cap is GBP 10.6bn.

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