Regulatory news

584 WHO Drug Information Vol. 30, No. 4, 2016 Regulatory news Pre-market assessment EMA publishes clinical reports E u r o p e a n U n i o n – The EMA has started to give open access to clinical reports for new medicines for human use authorized in the EU on a new website, following the adoption of a new policy after extensive consultation with stakeholders. The website will include the clinical reports contained in applications for marketing authorization submitted to the Agency on or after 1 January 2015, and in applications for extension or modification of an indication, or for line extension, submitted on or after 1 July 2015. The data is intended to increase transparency, facilitate independent re-analysis and support efficient medicine development. Data for two medicines were published initially, comprising over 100 clinical reports. EMA expects to offer access to approximately 4500 clinical reports per year. (1) Data for two additional medicines followed one month later. (2) Health Action International (HAI) has welcomed the move and has emphasized its strong support for the principle that clinical trial data must be made publicly available to all. (3) ► (1) EMA Press release, 20 October 2016. (2) EMA Press release, 24 November 2016. EMA. Online access to clinical data for medicinal products for human use. https:// clinicaldata.ema.europa.eu. (3) HAI. Clinical Trial Data Transparency on Trial – EMA Under Pressure From Pharma Lawsuit. 1 December 2016. Post-market surveillance Social media campaign on reporting of medicines side effects U n i t e d K i n g d o m , E u r o p e a n U n i o n – On 7–11 November 2016 the MHRA held a social media campaign to promote reporting of suspected side effects as part of an EU-wide awareness week. Twenty-two EU Member States took part in the combined cross-European social media campaign organized under the Strengthening Collaboration for Operating Pharmacovigilance in Europe (SCOPE) Joint Action project, which aims to raise awareness of national reporting systems for suspected side effects in medicines. ► UK Government Press release, 7 November 2016. EU project to strengthen market surveillance for medical devices B r a t i s l a v a , S l o v a k i a – At the 39th meeting of the EU Competent Authorities for Medical Devices (CAMD) held in Bratislava in October 2016, the MHRA launched the Joint Action on Market Surveillance of Medical Devices. Post- marketing surveillance is a crucial part of health product regulation to make sure that medical devices are acceptably safe and perform as intended. The project aims to improve the coordination of surveillance activities by EU member states and to ensure adequate communications and cooperation. ► MHRA News story, 17 November 2016. 585 WHO Drug Information Vol. 30, No. 4, 2016 Regulatory news EU–U.S. collaboration on medicines for rare diseases E u r o p e a n U n i o n , U n i t e d S t a t e s o f A m e r i c a – The EMA and the FDA have set up a new working group to share experiences and best regulatory practices in the development of medicines for rare diseases. Global collaboration in this area is particularly important to ensure that the few studies that can be conducted in the small patient populations can benefit all patients. The agencies will exchange information on topics such as the design of clinical trials and the use of statistical analysis methods, the selection and validation of trial endpoints, preclinical evidence to support development programmes, the design of post-marketing studies, and risk management strategies for long-term safety issues. The existing EMA/FDA “Cluster on orphan medicinal products” will continue to focus on orphan designation and exclusivity. ► EMA News, 26 September 2016. Japan joins international collaboration on GMP inspections The ongoing international collaboration on good manufacturing practice (GMP) inspections of manufacturers of active pharmaceutical ingredients (API) is to be expanded to include Japan’s Pharmaceutical and Medical Devices Agency (PMDA). The collaboration started as a pilot in 2008 and was fully implemented in 2011. It currently includes EMA, five regulatory authorities of EU Member States, the European Directorate of the Quality of Medicines and Healthcare (EDQM) the U.S. FDA, the TGA of Australia, Health Canada and WHO. The participating organizations share information on inspections of API manufacturers worldwide, including information on planning, policy and reports. The overall objective of the collaboration is to increase cooperation and mutual reliance between participating organizations to make the best possible use of inspection resources. ► EMA News, 25 November 2016. Mapping of global medicines regulatory initiatives E u r o p e a n U n i o n – The EMA has published a comprehensive overview of global initiatives on medicine regulation. The mapping was carried out by EMA on behalf of the International Coalition of Medicines Regulatory Authorities (ICMRA). The aim of the mapping exercise was to raise awareness of ongoing activities, provide a basis for strategic coordination and identify possible gaps. The report was presented at the 11th Summit of Heads of Medicines Regulatory Agencies and the annual ICMRA meeting held in Interlaken, Switzerland, on 11-13 October 2016. It includes wide-ranging activities such as the harmonization work of the International Council for Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH), and identifies areas of particular strategic interest for ICMRA including generic medicines, good manufacturing practice inspections, exchange of confidential information, supply-chain integrity, crisis management, pharmacovigilance and information technology systems. ► EMA News, 13 October 2016. EMA. Connecting the dots. Towards global knowledge of the international medicine regulatory landscape: mapping of international initiatives. 2016. Regulatory news WHO Drug Information Vol. 30, No. 4, 2016 586 MHRA and Swissmedic sign agreement I n t e r l a k e n , S w i t z e r l a n d – The MHRA and Swissmedic have signed a Memorandum of Understanding (MoU). The agreement was signed on the sidelines of the 11th Summit of the Heads of Medicines Regulatory Agencies in Interlaken, Switzerland. It focuses on implementing a shared approach to complex challenges and on promoting each other’s regulatory frameworks, requirements and processes, as a basis for information-sharing. ► MHRA Press Release, 11 October 2016. Swissmedic Announcement, 11 October 2016. Use of medicines Report on sales of veterinary antibiotics in Europe E u r o p e a n U n i o n – The Sixth report on the sales of veterinary antibiotics in Europe highlights a slight downward trend, suggesting that actions taken by EU member states to fight antimicrobial resistance are making a difference. A total of 28 countries reported data to the European Surveillance of Veterinary Antimicrobial Consumption (ESVAC) for the year 2014. While a considerable increase was noted in one European country due to an improvement in data collection systems, an overall decrease of 12% was found in 24 of the 25 countries that provided data for this four-year period. Other countries also changed their reporting systems or identified under-reporting, meaning that the findings should be interpreted with caution. ► EMA News, 14 October 2016. EMA. Sales of veterinary antimicrobial agents in 29 European countries in 2014. Sixth ESVAC report. Indian FDC ban reversed I n d i a – The Delhi High Court has stayed a government ban on 344 fixed-dose combination (FDC) medicines after more than six months of hearing more than 300 petitions filed by pharmaceutical companies. (1) The ban, which affected analgesic and antibiotic combinations among others, had been announced in March 2016 in the interest of public health. (2) ► (1) Reuters Money News, 1 December 2016. (2) Regulatory News. WHO Drug Information. 2016; 30 (2): 213. Under discussion E u r o p e a n U n i o n – The European Medicines Agency (EMA) has published a revised guideline on first-in-human clinical trials. The revision was based on a concept paper released for comment earlier in 2016 and took into account the lessons learnt from the tragic incident which occurred during a clinical trial in Rennes, France, in January 2016. The revised guideline is open for public consultation until 28 February 2017. ► EMA Press release, 15 November 2016. E u r o p e a n U n i o n – The European Commission (EC) is seeking views and feedback from stakeholders, to support the Commission in drafting its second report on the Paediatric Regulation after ten years of implementation.The consultation is open until 20 February 2017. ► EMA News, 15 November 2016.Under d 587 WHO Drug Information Vol. 30, No. 4, 2016 Regulatory news Approved Obeticholic acid: for rare, chronic liver disease Product name: Ocaliva® Dosage form: Tablets Class: Bile acid preparation; ATC code: A05AA04 Approval: EMA (orphan product; conditional approval) Use: In combination with ursodeoxycholic acid (UDCA), treatment of primary biliary cholangitis (also known as primary biliary cirrhosis) in patients who cannot successfully be treated with UDCA alone. Benefits: Ability to delay development of liver fibrosis, cirrhosis liver transplant and death through reduction of alkaline phosphatase and bilirubin levels in adults with primary biliary cholangitis. The efficacy remains to be formally demonstrated by means of post- authorization follow-up. Note: In the past, the only option for these patients has been a liver transplant. ► EMA Press release, 14 October 2016. Insulin aspart : for diabetes mellitus Product name: Fiasp® Dosage form: Solution for injection Class: Fast-acting insulin analogue; ATC code: A10AB05 Approval: EMA Use: Treatment of diabetes mellitus in adults Benefits: Ability to control blood glucose. Note: Fiasp® is an ultra-rapid-acting formulation of insulin aspart. ► EMA CHMP Summary of opinion, 10 November 2016. Insulin glargine/lixisenatide: for diabetes mellitus Product name: Suliqua® Dosage form: Solution for injection Class: Fixed-ratio combination of insulin glargine, a basal insulin analogue, and lixisenatide, a glucagon-like peptide 1 (GLP-1) receptor agonist Approval: EMA Use: In combination with metformin, treatment of diabetes mellitus in adults when glycaemic control has not been provided by other treatments. Benefits: Clinically relevant effect on glycaemic control in patients with type-2 diabetes when used with metformin. ► EMA CHMP Summary of opinion, 10 November 2016. Lonoctocog alfa : for haemophilia A Product name: Afstyla® Dosage form: Powder and solvent for solution for injection or infusion Class: Single-chain recombinant human factor VIII product; ATC code: B02BD02 Approval: EMA CHMP recommendation Use: Treatment and prophylaxis of bleeding in patients with haemophilia A. Benefits: Ability to prevent and control bleeding when used on demand and when used for surgical procedures in adults and children with haemophilia A. Lonoctocog alfa has demonstrated a higher affinity for von Willebrand factor (VWF) than full-length recombinant factor VIII. VWF stabilises factor VIII and protects it from degradation. ► EMA Summary of opinion, 10 November 2016. Etelcalcetide : for secondary hyperparathyroidism Product name: Parsabiv® Dosage form: Solution for injection Class: Synthetic peptide, calcimimetic agent ATC code: H05BX04 Approval: EMA Regulatory news WHO Drug Information Vol. 30, No. 4, 2016 588 Approved Use: Treatment of secondary hyperparathyroidism in adults with chronic kidney disease on haemodialysis therapy. Benefits: Ability to reduce abnormally elevated serum parathyroid hormone levels in patients with chronic kidney disease on haemodialysis therapy. ► EMA Summary of opinion, 15 September 2016. Tenofovir alafenamide: for chronic hepatitis B Product name: Vemlidy® Dosage form: Film-coated tablets Class: Nucleotide reverse transcriptase inhibitor; ATC code: J05AF13 Approval: EMA Use: Treatment of chronic hepatitis B in adults and adolescents aged 12 years and older. Benefits: Ability to achieve a sustained antiviral response in treatment-naive and treatment-experienced patients. Safety information: Lower impact on renal safety and bone mineral density compared to tenofovir disoproxil. ► EMA CHMP Summary of opinion, 10 November 2016. Olaratumab : for soft tissue sarcoma Product name: Lartruvo® Dosage form: Concentrate for solution for infusion Class: Human IgG1 monoclonal antibody and antagonist of platelet derived growth factor receptor-α (PDGFR-α) expressed on tumour and stromal cells; ATC code: L01XC27 Approval: EMA (orphan product, accelerated assessment; conditional marketing authorization): FDA (orphan drug; fast- track designation, priority review, break- through therapy, accelerated assessment) Use: In combination with doxorubicin, treatment of adults with soft tissue sarcoma. Benefits: Improved survival. Safety information: Olaratumab has some serious risks including infusion-related reactions and embryo-foetal harm. ► EMA Press release, 16 September 2016. FDA News release, 19 October 2016. Palbociclib: for breast cancer Product name: Ibrance® Dosage form: Hard capsules Class: Inhibitor of cyclin-dependent kinases (CDK) 4 and 6; ATC code: L01XE33 Approval: EMA Use: In combination with other medicines, treatment of hormone receptor (HR)- positive and human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer. Benefits: Improved progression-free survival. ► EMA Press release, 16 September 2016. Eteplirsen: for Duchenne muscular dystrophy Product name: Exondys 51® Dosage form: Injection for intravenous use Class: Antisense oligonucleotide: ATC code: M09AX06 (temporary code) Approval: FDA (orphan medicinal product, fast track designation; accelerated approval under a rare paediatric disease priority review voucher) Use: Treatment of patients with Duchenne muscular dystrophy with a confirmed mutation of the dystrophin gene amenable to exon 51 skipping. Benefits: Dystrophin increase in skeletal muscle (surrogate endpoint). Notes: The FDA has required a study to assess whether the product improves motor function. ► FDA News release, 19 September 2016. Baricitinib:: for rheumatoid arthritis Product name: Olumiant® Dosage form: Tablets 589 WHO Drug Information Vol. 30, No. 4, 2016 Regulatory news Approved Class: Selective and reversible inhibitor of Janus kinase (JAK) 1 and 2; ATC code: L04AA37 Approval: EMA Use: Treatment of active rheumatoid arthritis in adults who cannot be treated with other disease-modifying anti-rheumatic drugs. Benefits: Reduces the symptoms of rheumatoid arthritis EMA Press release, 16 Dec 2016. Naloxone nasal spray : for opioid overdose Product name: Narcan® Dosage form: Nasal spray Class: Antidote; ATC code: V03AB15 Approval: Health Canada (expedited review) Use: Emergency treatment of opioid overdose (non-prescription use) Notes: Since early 2016, naloxone is available without a prescription in Canada for emergency treatment of opioid overdose. A temporary import permit for a U.S. FDA-approved product was granted in July 2016. ► Government of Canada News release, 3 October 2016. Edotreotide: for diagnosis of gastro- entero-pancreatic neuroendocrine tumours; Product name: SomaKit TOC® Dosage form: Kit for radiopharmaceutical preparation Class: Diagnostic radiopharmaceutical for tumour detection; ATC code: V09IX09 Approval: EMA (orphan product) Use: After radiolabelling with gallium (68Ga) chloride solution, for Positron Emission Tomography (PET) imaging of somatostatin receptor overexpression in adult patients with well-differentiated gastro-entero-pancreatic neuroendocrine tumours. Benefits: Ability to localize primary tumours and their metastases. ► EMA Summary of opinion, 13 October 2016. Biosimilars Insulin glargine Product name: Lusduna® Reference product: Lantus® Approval: EMA Use: Treatment of diabetes mellitus ► EMA/CHMP Summary of opinion, 10 November 2016. Teriparatide Product name: Movymia® Reference product: Forsteo® Approval: EMA Use: Treatment of osteoporosis ► EMA/CHMP Summary of opinion, 10 November 2016. Product name: Terrosa® Reference product: Forsteo® Approval: EMA Use: Treatment of osteoporosis ► EMA/CHMP Summary of opinion, 10 November 2016. Rituximab Product name: Truxima® Reference product: Mabthera® Approval: EMA Use: treatment of non-Hodgkin’s lymphoma, chronic lymphocytic leukaemia, rheumatoid arthritis, granulomatosis with polyangiitis and microscopic polyangiitis. ► EMA Summary of opinion, 15 December 2016. Adalimumab-atto Product name: Amjevita® Reference product: Adalimumab (Humira®) Approval: FDA (biosimilar, not interchangeable with Humira®) Use: Treatment of multiple inflammatory diseases in adult patients. Regulatory news WHO Drug Information Vol. 30, No. 4, 2016 590 Approved Safety information: Boxed Warning about an increased risk of serious infections, lymphoma and other malignancies, including some fatal ones, in children and adolescent patients treated with tumour necrosis factor blockers, including adalimumab products. ► FDA News release, 23 September 2016. Extension of indications Empagliflozin: to reduce cardiovascular risk in diabetes Product name: Jardiance® Approval: FDA Newly approved use: To reduce the risk of cardiovascular death in adults with type 2 diabetes. Notes: Empagliflozin is not intended for patients with type 1 diabetes or for the treatment of diabetic ketoacidosis. It is contraindicated in patients with a history of serious hypersensitivity reactions to the medicine, severe renal impairment, end- stage renal disease, or those on dialysis. ► FDA News release, 2 December 2016. Maraviroc : for use in children Product name: Selzentry® Approval: FDA Newly approved use: For the treatment of CCR5-tropic human immunodeficiency virus type 1 (HIV 1) infection in patients 2 years of age and older weighing at least 10 kg. Note: Maraviroc is not recommended in patients with dual/mixed- or CXCR4-tropic HIV-1. ► What’s New at FDA in HIV/AIDS. Bulletin, 7 November 2016. Nivolumab: for Hodgkins lymphoma Product name: Opdivo® Approval: EMA Newly approved use: Treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma after autologous stem cell transplant and treatment with brentuximab vedotin. ► EMA/CHMP Summary of opinion, 13 October 2016. Canakinumab : for rare and serious auto-inflammatory diseases ; Product name: Ilaris® Approval: FDA Newly approved use: Treatment of Tumour Necrosis Factor Receptor Associated Periodic Syndrome (TRAPS); Hyperimmunoglobulin D Syndrome (HIDS)/Mevalonate Kinase Deficiency (MKD); and Familial Mediterranean Fever (FMF) in adults and children. Note: Canakinumab was previously FDA- approved for another periodic fever syndrome called Cryopyrin-Associated Periodic Syndromes (CAPS) and for active systemic juvenile idiopathic arthritis. ► FDA News release, 23 September 2016. å