EMA Draft ‘Strengthens’ Guidance on Safety Follow-Up for Advanced Therapies

February 12, 2018

The EMA published a draft revision to its guideline for clinical trials follow up of advanced therapy medicinal products, including gene therapies, cell therapies and tissue engineered products. The draft strengthens and clarifies the EMA’s 2008 guideline, and includes more details on designing post-authorization safety and efficacy follow-up studies. Sponsors need to provide safety and efficacy follow-up data in their marketing applications, including long-term data to analyze the benefits and risks of products. Objectives for safety follow-ups should be based the on specific product characteristics than on its classification, such as whether it is a cell- or gene-based therapy, or a combination. The evaluation of the long-term efficacy is a key issue for gene therapies as premarket clinical trials typically include a limited number of patients and with a limited duration. The EMA suggested sponsors provide long-term follow-up data in several situations, such as for cell therapies with a short shelf life, which may require monitoring of efficacy and the need for re-administration. Immunogenicity is also a critical consideration for the efficacy assessment of a cell-based product. The EMA’s draft guideline is available here:

NIH Partners with Industry to Identify Parkinson’s Disease Biomarkers
Citing the numerous failures in clinical trials, the NIH will collaborate with government, biopharmaceutical, life science and nonprofit organizations to help advance the development of Parkinson’s disease (PD) treatments, as part of the NIH Accelerating Medicines Partnership. The initiative will focus on identifying and validating biomarkers to track the progression of PD and could serve as biological targets for the development of new drugs. “Advancing treatments for Parkinson’s disease is hampered by insufficient understanding of biological networks; drugs aimed at seemingly promising therapeutic targets fail in clinical trials,” said NIH Director Francis Collins. Due to increased life expectancies, the number of people with PD worldwide is expected to nearly double by the year 2030, according to the NIH. No disease-modifying drugs have yet been approved. The program will include Celgene, GlaxoSmithKline, The Michael J. Fox Foundation for Parkinson’s Research, Pfizer, Sanofi and Verily, which plan to invest a combined total of $12 million over five years through the Foundation for the NIH, which will manage the project. The groups plan to share de-identified data and findings among themselves and the research community, analyzing datasets from more than 3,000 cases and 1,700 healthy controls from studies funded by NINDS and MJFF, including the Parkinson’s Progression Markers Initiative.

SPIRIT Publishes 16 PRO Additions to Protocol Checklist
An international collaboration of clinical trialists, methodologists, journal editors and ethicists developed a new series of consensus-based guidelines for including patient-reported outcome measures in study protocols. The SPIRIT Group (Standard Protocol Items: Recommendations for Interventional Trials) identified 16 new PRO-related additions and changes for its 2013 checklist, which recommends a minimum set of evidence-based provisions that should be included in trial protocols. The extension was published in JAMA. The 16 items — including the specification of eligibility criteria, sample sizes, data collection plans, analysis methods and the individual responsible for PRO content — should be routinely addressed in all clinical trial protocols where PROs are a primary or secondary outcome, the group said. Other items recommend justifying the instrument used, including descriptions of the number of items, scaling and scoring, as well as plans for handling multiplicity issues. In an accompanying editorial, three researchers from the Icahn School of Medicine at Mount Sinai said the SPIRIT guidance will enable a more uniform approach to the collection and reporting of PRO data. They wrote, “PROs are essential as important outcome measures that matter to patients and will need to be incorporated in a systematic and standardized way in clinical trial protocols.” SPIRIT’s PRO extension is available:

EMA Prevails Against Drugmakers Seeking to Block Release of Clinical Trial Data
A European Union court ruled the EMA can offer access to clinical trial data in a blow to three drugmakers who argued this would hurt their business. The EMA had announced the release of the documents in response to third-party requests in accordance with European Commission transparency regulations. Merck and PTC Therapeutics had argued the EMA was not entitled to allow access to the trial data as it would risk their trade secrets, while Pari Pharma attempted to block the release of an EMA committee report on one of its drugs based on similar claims. However, the Court of Justice of the European Union ruled the companies did not provide sufficient evidence the releases would hurt their business. The EMA will “continue to diligently assess each individual request for access to documents submitted under the Transparency Regulation and in accordance with its policy on access to documents,” the agency said, following the decision.