Euro Roundup: EMA officials argue against making single pivotal trials the ‘rigid, default position’
Emer Cooke and other EMA leaders have weighed into the debate about whether sponsors should run one or two pivotal trials, arguing that the decision should be informed by the evidence needed to show a positive benefit-risk balance.
Cooke, executive director at EMA, and colleagues set out their views in a Nature article titled “Two trials or not two trials? That should not be the question.” Single pivotal trials can, and increasingly do, provide enough evidence to support approval decisions. However, Cooke and her colleagues discouraged drug developers from being “guided by the notion of a standard number of pivotal trials.”
“Developers should establish what evidence is already available, determine knowledge gaps, and plan evidence generation to answer well-formulated research questions with the aim of demonstrating that the benefits of the medicine outweigh its risks,” EMA leaders wrote.
EMA’s intervention in the debate comes seven months after Marty Makary and Vinay Prasad, who were then leaders at the US Food and Drug Administration, called for one pivotal trial to be the new standard. Responding to proponents of a one-trial standard, EMA leaders said, “such a rigid, default position would undermine the fundamental aims of the clinical development program.”
EMA starts consultation into requirements for systemic sclerosis clinical trials
The European Medicines Agency (EMA) is seeking feedback on requirements for clinical trials of drugs to treat the rare, chronic disease systemic sclerosis (SSc).
Last year, the European Alliance of Associations for Rheumatology published updated recommendations for treating SSc. Lacking a scientific guideline on the rare connective tissue disorder, EMA responded to the recommendations by publishing a draft concept paper. The draft set out the need for EMA to create a reflection paper about the clinical development of SSc treatments.
EMA published the draft reflection paper last week, starting a consultation that runs to 31 March. The reflection paper covers patient selection, efficacy assessment, trial design, safety, and studies in seniors and children, providing a high-level description of the requirements in each area.
Potential endpoints include measures related to organs affected by SSc, physician- and patient-reported assessments, and overall survival (OS). Sponsors should capture OS data and present them in filings for approval of new SSc treatments.
“It is acknowledged that to reliably assess this, randomized clinical studies of longer duration with a larger number of patients are needed,” EMA said. “Nonetheless, even if a claim of prolonged survival is not made, effects on mortality should be captured and reported at least in a descriptive manner. This can be done in an open-label extension phase, to supplement data collection in a controlled part of a trial.”
EMA adopts ICH bioequivalence guideline for immediate-release dosage forms
EMA’s Committee for Human Medicinal Products has adopted international guidelines on bioequivalence for immediate-release solid oral dosage forms.
The International Council for Harmonisation (ICH) M13B guideline provides recommendations on obtaining waivers of bioequivalence (BE) studies for one or more additional strengths of a drug product. Companies may be eligible for biowaivers when in vivo pharmacokinetic BE or efficacy and safety have been shown for at least one strength. Biowaivers could cut the need for additional in vivo BE studies.
ICH’s guideline applies to orally administered immediate-release solid dosage forms designed to deliver drugs to the systemic circulation, such as tablets, capsules, and granules or powders for oral suspension. Companies can obtain biowaivers during development and after approval.
The guideline covers the biowaiver criteria, addressing topics such as the selection of biobatch strengths and comparative dissolution. Another section focuses on specific topics, including fixed-dose combination drug products and when in vivo BE is needed at multiple strengths.
ICH’s guideline will take effect in Europe on 17 March.
MHRA launches £20M program to create regulatory science centers of excellence
The Medicines and Healthcare products Regulatory Agency (MHRA) has started a £20 million ($26 million) program to strengthen the UK’s capability and agility in regulatory science.
Using the money, MHRA and its collaborators will create four Centres of Excellence for Regulatory Science and Innovation (CERSIs) and fund their operations for up to five years. MHRA envisions CERSIs bringing together expertise from academia, industry, healthcare, and regulation to address emerging regulatory challenges and support the safe adoption of new innovations.
MHRA has identified four areas where regulatory science capabilities are needed: data-driven approaches and artificial intelligence; prevention, early detection, and novel evidence approaches; personalized healthcare and pharmacogenomics; and novel platform technologies.
UK research organizations eligible for Medical Research Council funding can apply for money to establish a CERSI. Successful applicants will initially receive three years of funding. An additional two years of funding may be available, depending on a government spending review and budget allocation.
EFPIA warns proposed EU cloud computing and AI rules could fragment research
EFPIA has cautioned that the European Commission’s proposed Cloud and AI Development Act (CADA) could fragment research.
The pharma trade group’s concerns center on the potential for CADA to limit access to globally available technologies or to constrain legitimate cross-border data processing. CADA is intended to strengthen Europe’s sovereignty and competitiveness in the cloud and AI ecosystem, for example by tripling its data center capacity within seven years.
EFPIA voiced support for the overall objective of increasing Europe’s capacity. However, the trade group warned against relying on a static list of pre-designated third countries that are eligible to provide certain cloud services. Instead, EFPIA wants officials to adopt an eligibility framework that is “sufficiently flexible and risk-based to reflect the global nature of research and innovation.”
Because companies routinely collaborate across borders, sovereignty requirements must “not become de facto data localization measures or create unnecessary barriers to collaboration with trusted international partners or the use of established global cloud and AI providers,” EFPIA said. The trade group also noted the need to prevent CADA from imposing duplicative or conflicting requirements.
MHRA seeks feedback on using AI to improve medicine safety evaluations
MHRA is holding an open call for evidence about using AI to predict and assess a medicine’s absorption, distribution, metabolism, excretion, and toxicity (ADMET).
AI could improve ADMET predictions and assessments by integrating preclinical, clinical, and real-world data, MHRA said. Predicting how medicines will affect the body and perform in real-world settings could help identify potential safety risks sooner.
MHRA wants to learn about how organizations are using, or planning to use, AI for ADMET and other safety assessments, as well as about the barriers or challenges they face. The survey covers model development, validation, access to data, data sharing, and regulatory considerations.
The call for evidence, which closes on 22 December, will inform development of the “Beyond ADMET: AI for medicines safety” regulatory sandbox and support other MHRA work in the area.
Other News:
The Swiss Agency for Therapeutic Products (Swissmedic) has updated its portal to allow users to view specialist data for complementary medicines in the notification procedure. The data relate to the basic company dossiers, master dossiers, and medicines associated with the user’s organization. Swissmedic Notice
EMA has recommended restricting the use of medicines containing ipidacrine. The restrictions will prevent use of the drugs in neuritis, polyneuritis, polyradiculoneuropathy, and myasthenic syndrome. The benefits still outweigh the risks in certain other indications, EMA concluded. EMA Notice
