Welcome to our European Regulatory Roundup, our weekly overview of the top EU regulatory news.

PRAC Recommends Antibiotics to Offset Zydelig Infection Risks                                           

The Pharmacovigilance Risk Assessment Committee (PRAC) has called for doctors to give antibiotics to cancer patients taking Gilead Sciences' Zydelig to offset the risk of lung infection. Regulators on both sides of the Atlantic have been looking at the safety profile of Zydelig following the detection of adverse events that have led to Gilead halting six trials of the PI3K inhibitor.

Gilead spotted the adverse events in three of its clinical trials, which were testing Zydelig in patients with chronic lymphocytic leukemia (CLL) and other forms of cancer. As Zydelig is approved for use in CLL in Europe, but in a different context than it was being used in the trial, the European Commission asked PRAC to review the safety of the drug. PRAC is still conducting the review, but, as an interim measure, has already told doctors it recommends prescribing an antibiotic alongside Zydelig to offset the risk of patients developing the lung infection Pneumocystis jirovecii pneumonia.

To assess whether the preventative measure is working, PRAC wants doctors to monitor patients for infection, particularly respiratory symptoms, and perform regular white cell counts. A decline in the number of white cells detected in a blood test is indicative of an increase in the risk of the infection, putting the patient at risk of contracting Pneumocystis jirovecii pneumonia or cytomegalovirus. Given these concerns, PRAC is advising against starting treatment with Zydelig in patients who show signs of ongoing systemic infection.

PRAC is also trying to limit the patient population in which Zydelig is used. As the CLL trial enrolled some patients who have the 17p deletion or TP53 mutation, PRAC is recommending doctors do not use the PI3K inhibitor as a first-line treatment in such patients in the real world. Similarly, PRAC wants to limit combination treatments with Zydelig to pairings with rituximab, and even then only in patients who have received one prior line of treatment. In follicular lymphoma, the other indication in which Zydelig is approved, use is limited to patients who are refractory to two lines of treatment.

The recommendations were made at a busy PRAC meeting earlier this month. At the event, PRAC also began a review into the use of direct-acting antivirals, such as Gilead's Sovaldi and AbbVie's Viekirax, in the treatment of chronic hepatitis C. The review follows reports that active infections of hepatitis B have reemerged in patients following treatment with direct-acting antivirals against the C type of the virus. PRAC also initiated a review into the risk of gadolinium deposition in the brain following magnetic resonance imaging scans and completed a probe into inhaled corticosteroids.

PRAC Release I More

EMA Elects Head of Austrian Regulator as Chair of the Board

The European Medicines Agency (EMA) has elected Dr. Christa Wirthumer-Hoche as chair of its management board for three years. Wirthumer-Hoche, who has lead the Austrian Medicines and Medical Devices Agency since 2013, takes over as chair from the long-serving Sir Kent Woods, who stepped down late last year.

In landing the position, Wirthumer-Hoche has gained influence over a board that is responsible for setting the EMA budget, approving the annual work program and ensuring the regulator works effectively with partner organizations, both within the European Union and the wider world. In an acceptance statement briefly setting out her objectives for the three-year term, Wirthumer-Hoche put the emphasis on the need for the various components of the European regulatory and political machinery to collaborate and cooperate effectively.

"As chair, my ambition is to ensure a strong partnership between EMA, the European Union national competent authorities and the European Commission to guarantee that EMA is able to fulfil its important role of safeguarding human and animal health in Europe," Wirthumer-Hoche said.

Wirthumer-Hoche has experience of working in several parts of the European regulatory system. In October 2013, Wirthumer-Hoche took over as head of the Austrian drug and device regulator, a position she still holds. Wirthumer-Hoche became a member of the EMA board the same month. Since then, Wirthumer-Hoche has taken on more and more responsibilities within EMA, notably by signing up as co-chair of the EU Network Training Centre in January 2015 and then taking over as vice chair of the board this time last year.

The experience has contributed to Wirthumer-Hoche winning election as chair. "As vice chair of the board, she has already demonstrated many times that she has the vision and leadership ability required for this important role," Guido Rasi, executive director at EMA, said.

EMA Statement

Medical Literature Monitoring Service Identifies 1,464 Adverse Event Reports in First Six Months

EMA has released figures from the first six months of phased introduction of its medical literature monitoring service. Over that period, the service has reviewed 115,550 literature references, leading to the addition of 1,464 adverse drug reaction reports referring to 756 individual cases.

Given that EMA's EudraVigilance holds 9.5 million reports referring to 6.2 million cases, the medical literature monitoring service is fairly insignificant in terms of scale, but it was still being rolled out during the six months being analyzed. EMA began the service in July, at which time it was limited to the monitoring of 50 pharmaceutical substance groups. In September, EMA expanded the scope of the program, bringing the number of substance groups being monitored up to 400.

The regulator set up the monitoring service on the 300 chemical and 100 herbal substance groups to lessen the need for marketing authorization holders (MAH) to report adverse events, but it will take time to assess its success in this regard. In total, EMA received more than 1.2 million adverse drug reaction reports last year, a 10% increase year on year. The number of reports filed directly by the public through MAHs and national authorities jumped 29% to 48,872.

EMA Report

MHRA Commits to Continuing Public Board Meetings After Successful Pilot

The United Kingdom's Medicines and Healthcare Products Regulatory Agency (MHRA) has committed to holding more partly-public board meetings. MHRA pilot tested the idea successfully last month, giving officials the confidence to open up the morning sessions of the regulator's next three meetings to the public.

When MHRA first proposed the idea in January, it committed to holding two public board meetings, the first of which took place last month. Now, having come through the first public meeting, MHRA is expanding the program. The morning sessions of MHRA board meetings in April, September and December will all be open to the public.

As part of the expansion, MHRA has increased the limit on the number of members of the public who can attend the meeting. MHRA now has space for 15 members of the public, compared to just 10 slots for the first meeting. Registration for the April meeting is now open, with spaces being given out on a first come, first served basis.

While the adjustments represent an expansion of MHRA's transparency agenda, the regulator is still keeping aspects of its board meetings closed from the public. After the open morning sessions, MHRA will hold private meetings in the afternoon, at which it discuss certain emerging regulatory issues and other matters it is unable or unwilling to speak about publicly.

MHRA Release