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Posted 07 April 2016 | By Nick Paul Taylor
Welcome to our European Regulatory Roundup, our weekly overview of the top EU regulatory news.
Member states of the European Union are set to revoke the marketing authorizations of fusafungine sprays. The action follows a Pharmacovigilance Risk Assessment Committee (PRAC)review that found the risks of serious allergic reactions associated with the antibiotic and anti-inflammatory nose and mouth spray outweigh the benefits.
PRAC’s ruling prompted officials at the Coordination Group for Mutual Recognition and Decentralised Procedures - Human (CMDh) to look into fusafungine sprays. CMDh, a group that examines questions relating to the marketing authorizations of medicinal products affecting two or more member states, has endorsed the revocation of the approval of the sprays. Having reached the consensus decision, CMDh now expects member states to enact PRAC’s recommendations and revoke the authorizations of fusafungine-containing medicines, all of which are approved at a national level.
The examination of fusafungine-containing sprays by the European Medicines Agency’s (EMA) PRAC began in September at the request of Italy. Such medicines have a long history of use in Europe, having been available in almost 20 countries for as long as 50 years. The products were used on a prescription and over-the-counter basis to treat an array of infections of the upper airways, including sinusitis, rhinitis, rhinopharyngitis, tonsillitis and laryngitis. However, in recent years thinking around the risks and benefits of the intervention have started to shift.
On one hand, the mild, temporary nature of upper airway infections has raised doubts about the benefits of using fusafungine-containing medicines in these indications. At the same time, evidence of risks has begun to mount. Some patients have suffered serious allergic reactions, including severe and sustained contractions of airway muscles. Such contractions, which are known as bronchospasm, can make it hard for a person to breathe. While rare, the serious nature of the allergic reactions is a significant concern when viewed in light of the relatively minor benefits associated with the product.
In the longer term, PRAC is concerned about the potential for fusafungine-containing medicines to induce antibiotic resistance. PRAC was unable to find evidence to prove fusafungine sprays can cause resistance, but, equally, it found no data to counter the hypothesis. At a time when the European Union is working in multiple areas to cut the risk of bacteria developing resistance to treatments, the risk that a product available over the counter could undermine these initiatives is likely to be taken seriously.
When paired to the side effects and weak benefits, the antibiotic resistance concerns tipped the risk-benefit balance further in favor of the revocation of the marketing authorizations. The task of following through on the plan now falls on member states, which have been given a timetable by CMDh to outline what needs to happen and by when.
EMA has increased the fees it charges applicants and marketing authorization holders. The increase, which affects all activities outside of pharmacovigilance, amounts to 0.2%, a figure that reflects the 2015 inflation rate as set in the Official Journal of the European Union.
Applicants who got their submissions to EMA by 31 March will be charged the old, lower rate. For organizations seeking scientific advice or protocol assistance, EMA is tying the cut-off point for the previous, lower rate to the date on which the request for support was validated. All annual fees that have anniversaries from 1 April onward will incur the new rate.
EMA has released a full breakdown of the new fees in a 72-page explanatory note. The document details the fees for various types of regulatory process, such as an application for which a full dossier needs to be presented, and also provides example scenarios to show how the costs of complicated filings can incur an array of additional charges.
Pharmacovigilance activities are absent from the document and exempt from the rate increase. EMA plans to revise the fees for this area of its operation on 1 July.
EMA Notice, Explanatory Note
The Committee for Medicinal Products for Human Use (CHMP) has recommended for approval GlaxoSmithKline’s gene therapy against the ultra-rare immune disorder adenosine-deaminase-deficient severe combined immunodeficiency (ADA-SCID).
CHMP made the recommendation in favor of GSK’s gene therapy, which is branded Strimvelis, after reviewing data from a 12-person clinical trial. Children born with ADA-SCID lack an immune system capable of fighting off bacterial, fungal or viral infections, resulting in many sufferers dying in the first two years of life. Stem cell transplants can enable the immune system to recover, but patients who lack a genetically matched donor currently have limited options. Strimvelis is intended to improve outcomes in this subpopulation of patients.
After an average of seven years of follow up, all of the 12 patients in the clinical trial are alive. While the study size is tiny compared to most pivotal clinical trials, CHMP, with the advice of the Committee on Advanced Therapies (CAT), has decided it is sufficient to support an approval in this instance. GSK will be required to supplement the clinical trial data by enrolling all patients who receive the gene therapy in a registry. This is intended to ensure the close long-term follow up CHMP thinks is needed to monitor the ongoing effects of Strimvelis.
The approval process for Strimvelis has been relatively straightforward compared to the experience of the first gene therapy to win approval in Europe, uniQure’s Glybera. CAT initially rejected the drug, only to reverse its opinion after reexamining the evidence. CHMP, however, decided against following CAT’s advice and delivered a negative opinion on the basis that, in its opinion, there were too few trial subjects to show statistical significance. In 2012, the European Commission asked CHMP to look again at Glybera, leading to the gene therapy being approved late that year.
EMA has released its recommendation for the composition of influenza vaccines for the 2016-2017 flu season. Following the World Health Organization’s (WHO) advice, EMA has picked two A strains for use in trivalent and quadrivalent vaccines, namely A/California/7/2009 (H1N1)pdm09 and A/Hong Kong/4801/2014 (H3N2)-like viruses.
Manufacturers of trivalent vaccines, which are designed to confer immunity against three strains of the flu virus, are also being advised to include a B/Brisbane/60/2008-like virus in their formulations. EMA is suggesting producers of quadrivalent vaccines add a B/Phuket/3073/2013-like virus to their products. The rollout of quadrivalent vaccines in Europe trailed slightly behind approvals in the US, but AstraZeneca and GlaxoSmithKline are now both cleared to sell such products in the country.
Regardless of the type of flu vaccine in question, EMA wants marketing authorization holders to file to update the composition of their centrally authorized seasonal influenza vaccines by 13 June. That timeline positions manufacturers to have their products ready in time for the 2016-2017 flu season, which typically begins sometime in the fall.
Tags: fusafungine, Glybera, EMA Regulatory Roundup, EMA fees
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