Welcome to our European Regulatory Roundup, our weekly overview of the top EU regulatory news.
EMA Starts Consultation on PRIME Accelerated Development Plan
The European Medicines Agency (EMA) has started a public consultation about its PRIME accelerated development proposal. EMA has designed the program to eliminate regulatory snags that could slow the progress of medicines that treat unmet needs or offer significant advantages over existing drugs.
Many of the proposals in PRIME, a name derived from the term 'priority medicines', are refinements and advancements of existing regulatory tools, notably the scientific advice and accelerated review processes that are already in place. Programs accepted into PRIME will receive written confirmation of their participation and possibly be eligible for accelerated assessment. Once in the program, firms will be assigned a rapporteur from the Committee for Medicinal Products for Human Use (CHMP).
The pairing of CHMP rapporteurs to drugs, which is intended to improve the continuity of support offered to companies and build knowledge of the program on both sides, is the first of several ways in which PRIME tightens the ties between industry and regulators. Companies in PRIME will also benefit from a kick-off meeting attended by experts from EMA scientific committees and working groups of relevance. The goal is to provide advice on the development plan and regulatory pathway.
As companies advance through development and hit key milestones, the PRIME program will offer scientific advice. Third parties, such as health technology assessment bodies and patients, could play a role in this process. The overarching goal of all of these actions is to cut the risk that a misstep in the development plan, particularly the clinical trial design process, will result in a good drug failing to generate the data it needs to win approval. Shortening development timelines is another goal.
EMA plans to use the eligibility criteria of the accelerated assessment procedure for PRIME, meaning that to take part companies must have preliminary clinical evidence that a drug could deliver significant benefits to patients. Before it starts accepting applications, EMA is holding a consultation on the proposal, the main features of which are detailed in a reflection paper. EMA is accepting public comments until December 23. The aim is to start PRIME in the first quarter of 2016.
Press Release, Draft Reflection Paper
CHMP Recommends Steps to Cut Risk of PML when Taking Tecfidera
CHMP has recommended steps to cut the risk of patients developing the brain infection progressive multifocal leukoencephalopathy (PML) while taking Biogen's multiple sclerosis drug Tecfidera. The EMA committee wants to see physicians take a complete blood count prior to starting treatment and every three months thereafter.
EMA's CHMP thinks the establishment of a baseline for lymphocyte levels and continued monitoring during treatment may prevent the immune systems of patients being compromised to the extent that they are vulnerable to PML. The thesis is based on the knowledge that the infection that causes PML, John Cunningham virus, is very common but only rarely harmful. Each of the three cases of PML most strongly linked to Tecfidera have occurred in people with very low lymphocyte levels.
CHMP is recommending that physicians reconsider the risk-benefit profile of Tecfidera if a patient's lymphocyte levels fall below 0.5x109/L for more than six months. The three patients who developed PML after taking Tecfidera and had no history of receiving other medications linked to the infection all experienced a prolonged slump in lymphocyte levels prior to the onset of the disease. Switching patients with such characteristics to other medicines could prevent PML from developing.
If the doctor and patient decided to continue treatment with Tecfidera despite prolonged low levels of lymphocytes, CHMP is encouraging physicians to monitor their subjects closely for signs of motor dysfunction and other new neurological symptoms. MRI scans may be part of this process. CHMP is recommending physicians have a baseline MRI of the patient before starting treatment. After that, further scans should be considered in line with recommendations from local and national bodies.
CHMP evaluated two other medicines during its assessment of the link between Tecfidera and PML. The drugs, Fumaderm and Psorinovo, are fumarate medicines, a class of products to which Tecfidera also belongs. Case reports have linked Fumaderm and Psorinovo, which are used to treat psoriasis, to the development of PML. The recommendations for Fumaderm and Psorinovo are similar to those for Tecfidera, but in some regards more stringent.
EMA Releases Plan to Prepare Companies for Changes to Pharmacovigilance System
EMA has released a change management plan to help companies prepare for upcoming changes to its pharmacovigilance system, EudraVigilance. The plan details the technical and business process changes companies must implement to comply with the slated enhancements to EudraVigilance.
Officials at EMA are working on the changes to bring EudraVigilance in line with the requirements laid out in the latest legislation covering pharmacovigilance and clinical trials. Once the new system is live, EMA expects EudraVigilance to offer better detection of emerging and evolving safety issues, improved data analysis tools, a simpler reporting mechanism for marketing authorization holders (MAHs) and other benefits. Work must be done before these benefits can be realized, though.
In its 42-page change management plan, EMA details what must be done and by when. The plan covers the next two years, over which time a revised EudraVigilance access policy will be released and an audit of the system will take place. EMA has pencilled in the completion of a successful audit for the fourth quarter of 2016. Within six months of the news being released, new EudraVigilance access policies and routing changes for individual case safety reports (ICSRs) will take effect.
The routing changes for ICSRs are one of the new features of EudraVigilance for which MAHs and national competent authorities (NCAs) must prepare. Once the changes take effect, NCAs and MAHs will no longer be advised to send ICSRs to each other. Instead, all ICSRs are to be submitted to EMA's EudraVigilance system, which will then send the documents on to relevant parties. EudraVigilance will still allow MAHs to share ICSRs among themselves and NCAs to send files to regional centers.
Press Release, Change Management Plan
EMA has recommended the approval of Amgen's Imlygic, the oncolytic cancer immunotherapy formerly known as T-Vec. The recommendation positions Imlygic to become the first cancer killing virus to come to market in Europe. EMA reviewed the virus under its advanced therapy medicinal product classification with support from the Committee for Advanced Therapies. EMA Notice
The Committee on Herbal Medicinal Products (HMPC) has released a revised public statement on the prioritization of the assessment of safety concerns linked to herbal substances. HMPC began the process to establish a list of herbal medicines with unfavorable risk-benefit profiles. The committee will make the assessment of these substances a low priority. Public Statement
EMA has warned against using the transplant medicine mycophenolate during pregnancy. The advice represents a significant strengthening of the warning label for mycophenolate, a drug used to stop transplant rejection that is sold under the brand name CellCept. Men and women taking the drug should use contraception and pregnancy tests are recommended. EMA Notice
CHMP has recommended the removal of warnings about fat distribution from the labels of multiple HIV medicines. The recommendation overturns a warning that was implemented in the early 2000s, at which time combinations of HIV medicines were linked to body fat changes. Recent analyses suggest the link does not apply to many HIV medicines. Press Release