European Medicines Agency
The European Medicines Agency (EMA) Management Board has recently agreed the policy on publication of clinical trial data, together with more user-friendly amendments proposed by EMA executive director Guido Rasi, that will not only allow the Agency to proactively publish clinical trial data that are submitted as part of marketing authorisation applications, but also give the possibility to download, save and print the trial data for academic and non-commercial research purposes.
In light of discussions at the Board, the wording of the policy, including practical arrangements for academic and non-commercial research users, will now be finalised with a view to its adoption by the Board through written procedure by mid-July 2014, and will be effective from 1 October 2014. Importantly, the Agency will ensure that the policy will not prejudice citizens’ rights under existing access to documents legislation and the new clinical trials regulation.
Since embarking on its plans for the proactive publication of clinical trial data, the Agency has aimed to achieve the broadest possible consensus among its stakeholders and their often competing views and interests. After an extensive consultation phase that took place between June and September 2013, the Agency carried out a second round of targeted consultation in May 2014 that showed broad support for the policy, but highlighted concerns over the proposed view-on-screen-only access.
The Agency’s policy is an important step forward towards achieving increased transparency in the regulation of medicines in Europe. It takes the Agency beyond its legal obligations and provides an unprecedented level of access to clinical trial data that are used as part of decision-making for new medicines.
The Board endorsed a proposal for the creation of an ad hoc Working Group on Veterinary Novel Therapies (ADVENT). The working group will address the need expressed by stakeholders for more guidance on new classes of veterinary medicines, such as cell therapies, monoclonal antibodies and bacteriophages. A novel approach is proposed for this group in view of the need to rapidly produce guidance on a range of topics using the minimum possible resources in recognition of the scarcity of experts within the network with knowledge of novel veterinary therapies. ADVENT will be composed of a small core group of experts which can be supplemented with groups of experts in the specific scientific area covered by the new guidance document.
This initiative is in line with the Agency’s efforts to support development of innovative medicines. It follows the opening up in November 2013 of the Agency’s Innovation Task Force to provide support to veterinary medicines during the early stages of their development.
The Management Board also adopted a revised process for assessing the eligibility of patients’ and healthcare professionals’ organisations to provide input to the Agency on general issues related to medicines. This process allows the Agency to identify the most appropriate organisations acting in the interests of European civil society. The eligibility criteria have been updated to align with increased transparency requirements, in particular on sources and level of funding and a code of conduct on their relationship with pharmaceutical industry.
The Board gave a positive assessment of the Agency’s operations in 2013, and of its management and internal control system. This analysis and assessment of the executive director’s annual activity report is carried out by the Board annually, as required by the Financial Regulation. The analysis highlights, among other topics, the Agency’s initiatives towards stronger interaction with health technology assessment bodies to facilitate patients’ access to medicines and the Agency’s new organisational structure designed to better support the scientific work of the EMA’s committees, improve partner and stakeholder relations, and facilitate data-sharing among the European medicines regulatory network.
EMA recommends conditional marketing authorisation for Translarna to treat Duchenne muscular dystrophy
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended granting a conditional marketing authorisation for Translarna (ataluren), an orphan-designated medicine for the treatment of Duchenne muscular dystrophy caused by nonsense mutations. Translarna is to be used in patients aged five years and older who are able to walk.
Duchenne muscular dystrophy is a genetic disease that gradually causes weakness and loss of muscle function. Patients with the condition lack normal dystrophin, a protein found in muscles. Because this protein helps to protect muscles from injury as muscles contract and relax, in patients with the disease the muscles become damaged and eventually stop working. There are currently no approved therapies available for this life-threatening condition and the current management of the disease is based on prevention and management of complications.
In the European Union (EU), approximately 18,600 people have Duchenne muscular dystrophy. The disease can be caused by a number of genetic abnormalities. Translarna is for use in the subgroup of patients whose disease is due to the presence of certain defects (called nonsense mutations) in the dystrophin gene, which prematurely stop the production of a normal dystrophin protein, leading to a shortened dystrophin protein that does not function properly. Translarna is thought to work in these patients by enabling the protein-making apparatus in cells to skip over the defect, allowing the cells to produce a functional dystrophin protein.
In January 2014, the CHMP originally adopted a negative opinion for Translarna, but at the request of the applicant, the CHMP started a re-examination of its opinion. Following careful consideration of all available evidence, including a re-analysis of the clinical data submitted by the company, the Committee concluded that the data available are sufficient to recommend a conditional marketing authorisation. Under the terms of the authorisation, the company will be required to provide comprehensive data from an ongoing confirmatory study.
Conditional marketing authorisation is an early access mechanism which allows the Agency to recommend marketing authorisation for medicines that address an unmet medical need for patients suffering from life-threatening diseases even if comprehensive clinical data are not yet available.
The applicant for Translarna is PTC Therapeutics Limited. The company is registered as a micro-, small- or medium-sized-enterprise (SME), and as such benefited from support and incentives offered by the Agency’s SME office.
Because Translarna has an orphan designation, the Agency provided free scientific advice to the applicant during the development of the medicine. Orphan designation and the associated incentives, such as free scientific advice or ‘protocol assistance’, are among the Agency’s most important instruments to encourage the development of medicines for patients suffering from rare diseases.
The CHMP opinion on Translarna will now be sent to the European Commission for adoption of a decision on an EU-wide marketing authorisation.
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended marketing authorisation for Gazyvaro (obinutuzumab) in combination with the cancer medicine chlorambucil for the treatment of adults with previously untreated chronic lymphocytic leukaemia.
Gazyvaro has an orphan designation. It is to be used in patients with additional medical conditions who cannot be treated with full dose fludarabine-based therapy.
Chronic lymphocytic leukaemia is a rare type of cancer which affects certain white blood cells called B-lymphocytes. It is a long-term debilitating and life-threatening disease as patients can develop severe infections. Chronic lymphocytic leukaemia accounts for approximately 30 per cent of adult leukaemias. In the European Union (EU), more than 62,000 people were diagnosed with leukaemia in 2012 and over 41,000 people died from the disease.
Chronic lymphocytic leukaemia remains an incurable disease. Treatments currently available generally induce remission, however the disease returns in nearly all patients.
Gazyvaro is a monoclonal antibody that targets B-lymphocytes, thereby helping the body’s immune system to kill the cancer cells.
The main study on which Gazyvaro’s recommendation is based is a phase III trial including 781 previously untreated patients with chronic lymphocytic leukaemia and coexisting medical conditions. The study showed that patients treated with Gazyvaro in combination with chlorambucil lived significantly longer without their disease getting worse compared to patients treated with chlorambucil alone (26.7 months versus 11.1 months) or rituximab plus chlorambucil (26.7 months versus 15.2 months). In addition, the risk of disease progression or death was reduced by 86 per cent when Gazyvaro was given with chlorambucil.
The safety profile of Gazyvaro was in accordance with what would be expected for a monoclonal antibody in this class. Infusion-related reactions, neutropenia and infections were among the most common adverse events reported. Some rare but serious adverse events were reported; however, the toxicity profile of Gazyvaro was considered acceptable in view of its benefits.
The applicant for Gazyvaro, Roche, received scientific advice from the CHMP during the development of the medicine. The advice pertained to quality, non-clinical and clinical aspects of the dossier.
The CHMP opinion on Gazyvaro will now be sent to the European Commission for adoption of a decision on an EU-wide marketing authorisation
The United States Food and Drug Administration (US FDA) simultaneously approved Takeda Pharmaceutical’s new biologic therapy Entyvio (vedolizumab) for the treatment of adults with moderately to severely active ulcerative colitis (UC) and Crohn’s disease (CD).
“Entyvio is a new option that works to block important contributors to the chronic inflammation that is a hallmark of ulcerative colitis and Crohn’s disease,” said Stephen B. Hanauer, managing director, medical director, Digestive Health Center, Northwestern University Feinberg School of Medicine. “The clinical trial programme evaluated the efficacy and safety profile of Entyvio and demonstrated that Entyvio has the potential to help adult patients with moderately to severely active UC or CD successfully manage their disease.”
Entyvio is now approved for inducing and maintaining clinical response and remission, improving endoscopic appearance of the mucosa, and achieving corticosteroid-free remission in adult patients with moderately to severely active UC who have had an inadequate response with, lost response to, or were intolerant to a tumour necrosis factor (TNF) blocker or immunomodulator; or had an inadequate response with, were intolerant to, or demonstrated dependence on corticosteroids. Entyvio is also approved for achieving clinical response and remission, and achieving corticosteroid-free remission in adult patients with moderately to severely active CD who have had an inadequate response with, lost response to, or were intolerant to a TNF blocker or immunomodulator; or had an inadequate response with, were intolerant to, or demonstrated dependence on corticosteroids.
“Patients with moderately to severely active ulcerative colitis or Crohn’s disease, and the healthcare professionals who care for them, need additional new treatment options,” said Douglas Cole, president, Takeda Pharmaceuticals USA, “Entyvio reflects an expansion of Takeda’s commitment to supporting patients with gastrointestinal disorders.”
The Entyvio dose regimen is 300 mg infused intravenously over approximately 30 minutes at zero, two and six weeks, then every eight weeks thereafter. Patients should be observed during infusion and until the infusion is complete. See dosage and administration section in full prescribing information.
In March, Entyvio received a positive Opinion for the treatment of adults with moderately to severely active UC and CD from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA), and Takeda is awaiting response from the European Commission on approval for Marketing Authorisation.
The Biologics License Application filing with the FDA was supported by the largest Phase 3 clinical trial programme conducted to date simultaneously evaluating both UC and CD patient populations in four clinical studies involving 2,700 patients in nearly 40 countries. Three of these studies were randomised, double-blind, placebo-controlled trials – GEMINI I (UC Trials I and II), GEMINI II (CD Trials I and III) and GEMINI III (CD Trial II). GEMINI I, II and III evaluated adult patients with moderately to severely active UC or CD who had an inadequate response or intolerance to immunomodulator therapy; inadequate response, loss of response, or intolerance to a TNF blocker; or were corticosteroid dependent or had an inadequate response or intolerance to corticosteroids.
Adverse reactions were reported in 52 per cent of patients treated with Entyvio and 45 per cent of patients treated with placebo (UC Trials I and II: 49 per cent with Entyvio and 37 per cent with placebo; CD Trials I and III: 55 per cent with Entyvio and 47 per cent with placebo). Serious adverse reactions were reported in 7 per cent of patients treated with Entyvio compared to 4 per cent of patients treated with placebo (UC Trials I and II: 8 per cent with Entyvio and 7 per cent with placebo; CD Trials I and III: 12 per cent with Entyvio and 9 per cent with placebo).
The most common adverse reactions reported with Entyvio (incidence greater than or equal to 3 per cent and greater than or equal to 1 per cent higher than placebo) were nasopharyngitis, headache, arthralgia, nausea, pyrexia, upper respiratory tract infection, fatigue, cough, bronchitis, influenza, back pain, rash, pruritus, sinusitis, oropharyngeal pain, and pain in extremities.
Bayer HealthCare announced that it will start sharing data from its clinical studies through the internet portal http://www.clinicalstudydatarequest.com. From now on, qualified researchers can request anonymised patient-level data from Bayer HealthCare sponsored clinical studies listed on the website.
By joining the portal, Bayer HealthCare is supporting efforts of the European Medicines Agency (EMA) to increase the transparency of data from clinical studies. As a member company of the pharmaceutical trade associations EFPIA and PhRMA, Bayer is following their declared principles on responsible clinical trial data sharing.
“Our commitment to clinical trial transparency reflects our will to foster scientific research and hence public health,” said Dr Joerg Moeller, member of the Bayer HealthCare Executive Committee and Head of Global Development. “Joining the electronic platform and providing access to anonymized patient-level data, protocols and clinical study reports is a further step towards increased transparency while maintaining patient privacy.”
Secured data access will be granted after approval of the research proposal by an independent scientific review panel. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 1, 2014. Bayer HealthCare is not involved in the decisions made by the independent scientific review panel. Bayer HealthCare will take all necessary measures to ensure that patient privacy is safeguarded, in accordance with applicable laws and regulations.
In addition to the data provided via http://www.clinicalstudydatarequest.com, Bayer HealthCare provides through its ‘Bayer Trial Finder’ available at http://www.bayerpharma.com information about Bayer HealthCare sponsored trials dating back to 2005. This public information first becomes available at the beginning of a clinical study and is updated throughout the conduct of the study. Generally, summaries of trials will be published within a year of study completion.
The joint EFPIA-PhRMA Principles for Responsible Clinical Trial Data Sharing are available at: