An article published in Regulatory Rapporteur describes the requirement to try innovative regulatory approaches to address access to medicines for patients with unmet medical needs. According to the authors success of these approaches will depend on the “early incorporation of patients’ views and preferences into clinical trial design and during benefit–risk evaluation and health technology assessment (HTA).” The article provides details on how rare disease patients are more readily available and are willing to take greater risk in order to receive early access to medications and believe that increasing the patients influence in the regulatory process will increase and benefit this process. Additionally the authors describe HTA involvement in access to new therapies and provide examples of how the HTA can be enhanced and how the industry and patients can be involved in strengthening this process.
On April 6, 2016, three new applications were approved for the “IRDiRC Recommended” label: the TREAT-NMD Advisory Committee for Therapeutics (TACT), the Care and Trial Site Registry (CTSR) and Online Mendelian Inheritance in Man (OMIM).
TACT is a unique multi-disciplinary international group of academic and industrial drug development experts as well as representatives of patient foundations and institutional governmental scientific research centers, who meet twice a year to review and provide guidance on the translation and development path of therapeutics programs in rare neuromuscular diseases with large unmet need.
CTSR is aimed to help the pharmaceutical industry and clinical investigators select trial sites as well as to help to identify potential partners for upcoming research projects. The CTSR provides information relevant to clinical trials in the field of neuromuscular and neurodegenerative diseases and to the assessment of ‘centers of expertise.’ The CTSR collects contact data, patient cohorts, availability of diagnostic tools and equipment, personnel and their clinical trial experience, care settings as well as research and education activities of a site. Funded by the European Union Neuromics project, the CTSR was expanded in 2013 to include neurodegenerative centres and now encompasses data on patient cohorts of 32 rare diseases.
OMIM is a knowledge base of human genes and genetic phenotypes comprised of over 23,000 structured free-text entries and used weekly by 60-100,000 individuals from all over the world. OMIM names new Mendelian diseases and, in general, splits phenotypes on a molecular basis. OMIM is the gold-standard for disease-gene relationships as documented in the literature and meeting criteria described in the first reference below.
IRDiRC Recommended is a quality indicator highlighting tools/ standards/ platforms or guidelines contributing to IRDiRC’s objectives. “IRDiRC Recommended” endorsements are by the IRDiRC Scientific Committees. It focuses on key resources for research communities to accelerate clinical translation. More information about this initiative can be found here.
An article published in Orphanet Journal of Rare Diseases has described the need for the development of an orphan device directive in Europe. The author has provided a historical perspective of breakthroughs in surgical devices. He has then outlined what a current orphan device directive should address, which includes post-marketing surveillance, incentives to stimulate research and development for innovative devices as well as centralization of safety/efficacy data collected from EU member states into EUDAMED : European Databank on Medical Devices to obtain comparative (cost)effectiveness and safety statistics.
The report by the European Commission takes stock of the incentives received by sponsors towards developing orphan medicinal products. The report provides the statistics that possibly endorse the success of these incentives. According to the report, between 2000 and September 2015, the European Medicines Agency (EMA) received 2302 applications for orphan designation, of which the Commission approved 1544 and 1227 are currently active. In the first 15 years of application of the Regulation, 951 protocol assistance procedures were completed, of which 264 involved small and medium enterprises. The EMA receives a special annual contribution from the EU budget to waive fees in part or in full, which till date amounts to €78.4 million.
For EU-funded research on rare diseases and OMPs, Orphan designation has been a requirement for the Framework Program funding since 2009. The report details that there was more than a 50 % increase in both the number of OMP applications submitted and the number of designations granted by Commission during 2009-2015, in comparison with 2000-2008. More than €620 million in funding was awarded by FP7 to over 120 research projects on rare diseases and OMPs. Horizon 2020 maintains strong commitment to fund research on rare diseases and OMPs. Additionally, the Commission launched the International Rare Diseases Research Consortium (IRDiRC) under FP7, in cooperation with its EU and international partners.
The report details the measures taken by individual member states towards encouraging OMP development. In the Netherlands, registration fees can be waived if the OMP is already registered in another Member State and the prevalence of the condition is less than 1:150,000. Orphan medication developers in France are exempt from certain taxes paid by pharmaceutical companies and allow claiming a high price with certain conditions. Last year, Belgium and the Netherlands launched a pilot project on the joint negotiation of OMPs. Spain and Sweden announced specific scientific advice procedures to benefit developers of OMPs. The Committee for Orphan Medicinal Products at the EMA, has established an international liaison in North America and Japan and also holds a monthly teleconference with the U.S Food and Drug Administration.
Finally the report lists all the products that received marketing authorizations as OMPs over the past 15 years, and its distribution per therapeutic area.
In the previous year the European Medicines Agency (EMA) set up a public consultation to develop a scheme to optimize the development and accelerated assessment of medicines of major public health interest. It was developed in consultation with the Agency’s scientific committees, the European Commission and its expert group on Safe and Timely Access to Medicines for Patients (STAMP) as well as the European medicines regulatory network. This scheme for priority medicines was called PRIME is characterized by enhanced interaction and early dialogue with medicine developers and the EMA.
The EMA has thus launched PRIME, where a medication can be chosen to benefit from this scheme, based on the unmet medical needs it fulfills and on early clinical data that the said medication produces. The EMA encourages applicants from the academic sector and micro-, small- and medium-sized enterprises (SMEs), who can apply earlier on the basis of compelling non-clinical data and tolerability data from initial clinical trials. Companies can also request fee waivers for scientific advice.
The EMA has outlined the process once a candidate medicine has been selected for PRIME which is described in detail on their website.