The European Medicines Agency’s (EMEA) Paediatric Committee (PDCO) had its hands full with paediatric investigation plans (PIPs) at its latest meeting last week. The PDCO adopted positive opinions on a total of six PIPs spanning a range of therapeutic categories from oncology to nutrition.
Delivering opinions on PIPs, as well as applications for waivers and deferrals from the requirements of the European Union’s regulation on medicinal products for paediatric use (No. 1901/2006), is the primary function of the committee that held its first meeting in July 2007 and ushered through its first PIPs last December.
Under the regulation that came into play in January 2007, companies seeking approval either for a new medicinal product or for a new indication, route of administration or pharmaceutical form of an existing patent-protected product must submit a PIP detailing their strategy for developing the drug in all subsets of the paediatric population. The trade-off for meeting the requirements of an agreed PIP is a six-month extension to the product’s supplementary protection certificate.
Waivers from these obligations are available where there is evidence that the drug or class of drugs is likely to be ineffective or unsafe in part or all of the paediatric population; the disease or condition targeted by the product occurs only in adult populations (‘class waivers’); or the drug concerned does not present a significant therapeutic benefit over existing treatments for paediatric patients.
The latest batch of PIPs given the all-clear by the PDCO were as follows:
– Novartis Europharm Ltd’s albumin interferon alfa-2b (Albuferon) in the therapeutic area of hepatology;
– Novartis Europharm Ltd’s recombinant human monoclonal antibody to human IL-1 beta in the therapeutic area of immunology;
– Sanofi Pharma/ Bristol-Myers Squibb Pharma’s EEIG’s clopidogrel hydrogen sulfate (Plavix) in the therapeutic area of cardiovascular diseases;
– Fresenius Kabi Deutschland GmbH’s N-acetyl-L-cysteine, L-alanine, L-alanyl-L-glutamine, L-arginine hydrochloride, glycine, glycyl-L-tyrosine, L-histidine, L-isoleucine, L-leucine, L-lysine acetate, L-methionine, L-phenylalanine, L-proline, L-serine, taurine, L-threonine, L-tryptophan and L-valine in the therapeutic area of nutrition;
– Pfizer Ltd’s lipoglycopeptide antibiotic dalbavancin in the therapeutic area of infectious diseases;
– Ark Therapeutics’ adenovirus-mediated herpes simplex virus-thymidine kinase gene in the therapeutic area of oncology.
Further details of these PIPs will be available when the opinions are converted into EMEA decisions and published on the agency’s website.
Due for publication shortly are decisions adopted by the EMEA on PIPs for Janssen Cilag International’s atypical antipsychotic paliperidone (INVEGA), in the field of psychiatry; and for Johnson & Johnson PRD’s broad-spectrum carbapenem antibiotic doripenem monohydrate (Doribax), in the therapeutic field of infectious diseases. These were among four PIPs positively reviewed by the PDCO at its meeting in February.
Waivers adopted
The EMEA also adopted decisions on product-specific waivers in all subsets of the paediatric population for NicOx S.A.’s anti-inflammatory Naproxcinod (naproxen nitrooxybutylester), in the field of rheumatology; and for Heidelberg Pharma’s orally administered 5-fluorouracil analogue fosfluridine tidoxil, in the therapeutic area of dermatology.
At its latest meeting the PDCO adopted a product-specific waiver for Eli Lilly and Company Ltd’s selective estrogen receptor modulator arzoxifene in the field of oncology, recommending that the obligation to submit data obtained through clinical studies with children be waived in all subsets of the paediatric population.
In other business, the paediatrics committee adopted an opinion on a list of class waivers for conditions that do not affect children and for which the requirement to submit a PIP can therefore be waived. This new opinion complements the first decision on a class-waiver list taken up by the EMEA last December.
The original list of symptomatic conditions (17 in total) included a number of cancers (e.g., treatment of lung, breast or prostate carcinoma, hairy cell leukemia and multiple myeloma), as well as neurodegenerative diseases (e.g., Alzheimer’s, Parkinson’s) and age-related conditions such as macular degeneration or menopausal disorders.
The PDCO has “followed a step-wise approach for the discussion and adoption of condition waivers”, it noted. “Once the list of class waivers was endorsed, the PDCO considered in a second step each individual new condition proposed to be included in the list of waivers during the public consultation phase and adopted a further list of waivers.” When the EMEA has given its approval, the list of waivers will be updated regularly as knowledge and science in the paediatric field advance.
Priority list
The committee also finalised an update of its priority list for studies into off-patent medicines under the paediatric regulation, in advance of the next call from the European Commission in July 2008 for funding through the EU’s Seventh Framework Programme.
As the PDCO explained, the priority list “helps to ensure that funds are directed into research of off-patent medicines for which there is a high need in the paediatric population”. The ultimate objective is that more of these medicines will be filed with the EMEA for a Paediatric Use Marketing Authorisation (PUMA), which allows 10 years of data protection for innovative uses of off-patent products.
The updated list comprises some 30 medicines in the therapeutic categories of gastroenterology, oncology, immunology, infectious diseases, neonatology, neuropaediatrics, child and adolescent psychiatry, metabolism/endocrinology, pain/anaesthesiology, the cardiovascular system, nephrology/urology and rheumatology.
The list was drawn up from a public health perspective, the PDCO noted. First, conditions with more acute therapeutic needs were identified, based mostly on the severity of the disease, the paediatric groups affected (with special priority for neonatals), the non-availability of treatment alternatives and the high prevalence of the disease in the paediatric population. Published therapeutic reviews of medicines used in children were then analysed to identify off-label products of therapeutic interest.
The updated list will shortly be released for public consultation on the ‘Medicines for children’ section of the EMEA’s website. The consultation period will run until 26 May 2008.
