Therapeutics


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9Watson, MS et al. Newborn screening: towards a uniform screening panel and system- Executive summary. Pediatrics 2006. 117, S296-307 and see http://www.hrsa.gov/advisory committees/mchbadvisory/heri tabledisorders/recommendedp anel/ published Dec 2011, with the addition of Congenital heart Disease and Severe Combined Immunodeficiency, recently approved to the Recommended Uniform Screening Panel. 10 De Ruijter, J et al. Heparan sulfate and derman sulfate deriveds disaccharides are sensitive markers for newborn screening for mucopolysaccharidoses types I, II and III. Mol. Gen. Metab. 2012. 107, 705-710. 11 Scott, CR et al.


Identification of infants at risk for developing Fabry, Pompe, or Mucopolysaccharidosis-I from newborn blood spots by tandem mass spectrometry. J Pediatr. 2013 (Epub ahead of print). 12Valayannopoulos, V and Wijburg, FA. Therapy for the mucopolysaccharidoses. Rheumatol, 2011. 50, 49-59. 13 Kaplan, P et al. Revised recommendations for the management of Gaucher disease in children. Eur. J. Pediatr. 2012 [Epub ahead of print]. 14 Gieselemann, V et al. Metachromatic leukodystrophy- an update. Neuropediatrics 2010. 41 (1), 1-6. 15 Miyamoto, BE et al. The potential investment impact of improved access to accelerated approval on the development of treatments for low prevalence rare diseases. Orphanet J Rare Dis, 2011. 6(49), 1-13. 16 Deegan, PB et al. Natural history of Fabry disease in females in the Fabry Outcome Survey. J Med Genet, 2006. 43, 347-352. 17 Sasinowski, F. Quantum of effectiveness evidence in FDA’s approval of orphan drugs (Cataloguing FDA’s Flexibility in Regulating Therapies for Persons with Rare Disorders). NORD, 2011, 238-263.


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orphan drugs in the US has shown that the FDA has applied regulatory flexibility during the approval process in a number of cases17 – although it is unclear how many products were discontinued in earlier phases due to the challenges of drug development in rare diseases. A continued strengthening of the FDA Rare Disease Program could also facilitate progress by further educating and informing individual review divisions who may more frequently deal with higher prevalence diseases, and by this office being more directly involved in the development and review of orphan drug applications.


Bearing in mind the limited opportunity to run large or multiple clinical studies for rare diseases, it is encouraging that 62% of orphan drug applica- tions were submitted in parallel in the US and EU, and that regulatory authorities in different regions are starting to look for opportunities to co-ordi- nate activities and align thinking on these applica- tions. It would have a major impact on the ability of sponsors to rapidly bring forward therapies for patients suffering from rare diseases if there could be one consistent global assessment of an appro- priate regulatory path. Likewise, it is a positive step that initiatives such as the International Rare Disease Research Consortium (IRDiRC), which has representation from research funding bodies around the world, is co-ordinating investments aimed at supporting the approval of novel orphan drugs and diagnostics for rare diseases. There has been much success since the first orphan drug legislation 30 years ago, and the future is bright for the development of drugs to treat rare diseases. The field of genomics continues to rapidly advance, and in the near future this can be expect- ed to provide further insights into the nature of rare genetic diseases and increased understanding of the link between genotype and specific clinical pheno- types. We are also seeing advances in the develop- ment of new therapeutic modalities (eg gene thera- py, antisense therapeutics, tissue-engineered prod- ucts, cell therapies) which have particular utility for the treatment of rare genetic diseases. However, the past 30 years have also provided important learn- ings about the unique challenges in clinical devel- opment for rare diseases, and how these impact on the regulatory process. These should result in fur- ther consideration of the application of natural his- tory studies, newborn screening and early diagno- sis, surrogate markers of disease, as well as novel clinical trial designs. Most importantly, a key to the future in realising the hopes of patients who suffer from rare diseases and their families is active engagement and alignment on these important


issues between key stakeholders in the development of rare disease therapeutics, including industry, reg- ulatory authorities, research funding bodies and patient associations.


DDW


Dr Philip J. Vickers is Senior Vice President and Head of Research and Development at Shire Human Genetic Therapies (HGT). Dr Vickers is responsible for overseeing preclinical research, clinical development, regulatory affairs and med- ical affairs at Shire HGT. He oversees the organi- sation’s growing pipeline of rare disease therapies and plays a key role in developing and executing HGT’s global business strategy. Dr Vickers has more than 23 years of experience in the pharma- ceutical industry. He joined Shire from Resolvyx Pharmaceuticals where he was Chief Scientific Officer and President. Prior to this he was Senior Vice President and US Head of Research at Boehringer-Ingelheim Pharmaceuticals, where his team focused on therapeutic areas of Cardiovascular and Immunology & Inflammation. Before Boehringer-Ingelheim, he spent more than 13 years with Pfizer in a number of R&D leader- ship positions of increasing responsibility in the US and UK. These roles included drug discovery lead- ership across therapeutic areas, and leading the Pfizer Research and Technology Center in Cambridge, MA. He started his career with Merck Frosst in Canada, where he played a key role in the successful leukotriene and cyclooxygenase pro- grams. Dr Vickers holds a PhD in Biochemistry from the University of Toronto and a Bachelor of Science degree in Applied Biochemistry from the University of Salford, Manchester. He was also a Visiting Fellow at the National Cancer Institute in Bethesda, Maryland.


Drug Discovery World Spring 2013


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