European Regulatory Round Up: While EMA Opens Up, European Pharma Battens Down For Tough Year

The European Medicines Agency is focusing on transparency and pharmacovigilance over the next year, while the pharmaceutical industry is gearing up for a fight against austerity measures.

Each month, “The Pink Sheet” highlights key regulatory developments across Europe, selected by our European editors.

European Union News

EMA Transparency Drive Begins in Earnest – How Far Will It Go?

Beginning March 1, the European Medicines Agency will publish more information on ongoing drug product evaluations, part of a pledge to increase its transparency. The first step toward transparency was EMA’s orphan drugs data initiative, which provides information on orphan medicines under review in monthly reports. EMA is still grappling with how to shield certain types of commercially sensitive company information when making more data available (Also see "EMA Transparency Gathers Pace With A Flexible Definition Of Confidential Information" - Pink Sheet, 5 Jul, 2011.).

Under the new initiative, interested parties will be permitted to see the international non-proprietary name (INN) for the product under evaluation, the therapeutic areas for which it is intended and information on the type of salt, ester, or derivative of the active substance. All the details will be updated after the monthly meeting of the Committee for Medicinal Products for Human Use (CHMP). The information disclosures will include proprietary company information.

In the second half of the year, EMA will start publishing the agendas and minutes of its committee meetings. Here too, the agency is evaluating how far the openness will go. It will publish comprehensive information on the workings of some of its committees, but the minutes of the scientific committees, such as the CHMP and the Pharmacovigilance and Risk Assessment Committee, will have to be redacted in order to remove commercially sensitive information. “A discussion as to what is classified as commercially sensitive is ongoing,” EMA said

EMA Enters Member State Territory In 2012 Pharmacovigilence Work Plan

The European Medicines Agency is moving into new territory with its work plan for 2012, published in early February. In implementing new pharmacovigilance legislation, EMA will for the first time be involved in pharmacovigilance for products authorized by European Union Member States.

In the past, EMA focused on some 600 centrally authorized products. Now, it will have to deal with an estimated 80,000 adverse drug reaction reports annually and maintain a list of product information for every drug available in the EU. Manufacturers also need to tighten their pharmacovigilance game, given that the EMA will be focusing on integrating benefit/risk information after a product is authorized by placing increased emphasis on risk management plans.

Benefit/risk will also become more important in drug companies’ Periodic Safety Update Reports, designed to help continuously monitor products on the market. The PSUR program is being reevaluated so that companies would focus on providing them for drugs deemed at high safety risk, in place of the current requirement of reporting on all products at fixed periods of time.

The EMA Work Programme 2012 also provides for the future expansion of the EU. Within the framework of the Instrument for Pre-Accession Assistance (IPA), the EMA will allow for limited participation in its activities from Albania, Bosnia-Herzegovina, the former Yugoslav Republic of Macedonia, Kosovo, Montenegro, Serbia and Turkey. But while these countries will only be allowed observer status, Croatia, which is set to become the EU’s 28th Member State on July 1, 2013, will send “active observers” to EMA meetings, who will be permitted to attend the high-level CHMP meetings.

EMA Uses Rare Mechanism To Recommend Malaria Drug

Employing a scarcely used mechanism for pharmaceutical access, the European Medicines Agency has recommended Shin Poong Pharmaceutical Co. Ltd.’s Pyramax (pyronaridine-artesunate), a novel artemisinin-based combination therapy (ACT), for the treatment of malaria outside the EU. It is the first ACT registered to treat the two most prevalent and virulent strains of malaria (P. falciparum and P. vivax) and represents a breakthrough, particularly for sufferers in India and Southeast Asia.

The rare access mechanism allows the EMA to give a scientific opinion in co-operation with the World Health Organization on products that prevent or treat diseases of major public health interest, such as HIV/AIDS, malaria and tuberculosis. To date, only three other products have been recommended this way, all HIV treatments: Abbott Laboratories Aluvia (lopinavir/ritonavir), and ViiV Healthcare ’s lamivudine and lamivudine/zidovudine (known as Combivir in the U.S.).

In October 2007, GlaxoSmithKline PLC withdrew an application for a scientific opinion within this framework for its diphtheria/tetanus/pertussis/hepatitis B/’invasive’ diseases vaccine, Globorix. While GSK said that the drug did not fit in with the WHO vaccination strategy, the CHMP was seen as leaning towards a negative scientific opinion.

Novartis Turns Away From EMA’s Potential Second Pediatric Authorization

Novartis AG has withdrawn from EMA its application for a pediatric use marketing authorization (PUMA) for its FluadPaediatric influenza vaccine.

While the PUMA program was expected to be used only occasionally, just one PUMA has been granted since the mechanism was introduced in 2007 – for ViroPharma Inc.’s Buccolam (midazolam), a short-acting benzodiazepine in oromucosal solution intended for the treatment of acute seizures in children (Also see "EMA's First PUMA Recommendation Is One Small Step For Kids" - Pink Sheet, 6 Jul, 2011.). PUMAs are available for medicines intended for use exclusively in a pediatric population, but which may be based on authorized products for which a patent or supplementary protection certificate has already expired.

Novartis said that it felt obliged to withdraw its influenza vaccine application because it would be unable to answer the questions put to it by the CHMP within the time it had for responding. EMA has not yet released details of those questions but the information is expected to be published soon.

News From Member States

German Pharma Demands Reduced Rebates In Light Of Insurer Surpluses

The huge surpluses enjoyed this year by the German statutory health insurance funds (GKV) have made them a target for both the pharmaceutical industry and the federal health ministry. Big pharma companies want the government to cancel the 16% discount on drug products they are required to provide to the GKV. Health Minister Daniel Bahr is proposing instead that the funds return payments to their members. The GKV funds enjoyed billions of euros in profits in 2011.

For pharmaceutical manufacturers, it seems that the pill is becoming even tougher to swallow. The German pharmaceutical industry association, the VFA, sees little sense in either the health minister’s approach or a proposal by the country’s finance minister to withdraw the government’s contribution to the health care fund, which is provided to help stabilize the GKV. VFA Director General Birgit Fischer noted that while the government was looking to extract or redistribute funding, pharmaceutical manufacturers were being forced to continually pay into the GKV pot through the mandatory rebate mechanism (Also see "Germany To Disclose Rx Pricing Discounts, Setting A Potential Benchmark For Europe" - Pink Sheet, 7 Feb, 2012.).

Health insurers have refused to countenance either Bahr’s or the VFA’s proposals and may see good reason to hold out. A report published recently by consulting firm McKinsey suggests that the surplus will halve in 2013 and turn into a deficit in 2014. Any changes to GKV funding mechanisms would require approval by the German Parliament.

Italian Pharma Balks At Making Repayments For 2010

The Italian pharmaceutical industry is balking at the Italian national medicines agency (AIFA)’s demands that companies refund spending for drug products and pay back money used to purchase drug products that inadvertently broke a government ceiling imposed on pharmaceutical expenditure in 2010. Given the precarious situation of Italy’s economy, the industry says it is in no state to make the payments, which could lead to further job losses.

AIFA’s demands are based on a law that was supposed to cut €800 million from the pharmaceutical budget in 2010 by reducing spending on drugs from 14% to 13.3% of the overall health care bill.

Farmindustria, the pharmaceutical industry association, notes that AIFA did not meet the law’s own deadline for seeking payments and serious concerns about the quality of the data used to make the repayment calculations. Farmindustria also points out that such a request impairs companies’ financial planning, particularly in a country where the length of delays in payments to manufacturers has increased by 30% in the last two years and can last as long as 700 days. And the industry is already reeling from new reference pricing measures that will cost it €650 million in lost revenues over the year on top of €2.4 billion it had lost from previous pricing pressures (Also see "The Year Ahead In Europe: More Price Cuts, More Austerity" - Pink Sheet, 9 Jan, 2012.).

U.K. Medicines Lottery May Have Losing Hand

The end of U.K. regional variations in pharmaceutical coverage – known as the post code lottery – may be in sight, with the National Institute for Health and Clinical Effectiveness aiming to help local health reimbursement trusts in developing their drug formularies via a best practice guide. The formularies of preferred or selected drugs are expected to help standardize access to drugs and overcome the trusts’ practice of challenging or refusing to implement NICE drug coverage recommendations.

NICE’s actions were prompted by a Department of Health report recommending that formulary processes should proactively consider the impact of new NICE Technology Appraisals. Furthermore, it stresses that all NICE Technology Appraisal recommendations should, where clinically appropriate, be automatically incorporated into local formularies.

But local trusts are likely to resist the pressure to conform, if only for budgetary reasons. However, sitting NICE Deputy Chief Executive Gillian Leng said “NICE-approved drugs should not be excluded from local formularies on the grounds of cost. We want all patients to have access to medicines that we consider to be effective.” Unless the best practice guidance is accompanied by sanctions for local noncompliance, it is difficult to predict how effective this attempt at harmonization will be.