WHO Drug Information Vol. 28, No. 4, 2014

Regulatory news

Ebola curative – transfusions of whole blood or blood plasma from recovered patients Update on treatments and vaccines have been scheduled to be conducted in Liberia, in line with WHO technical The Ebola crisis has prompted an guidelines (4). unprecedented cooperation between regulators In September the European Medicines to support WHO and to advise on possible Agency (EMA) established an expert pathways for the development, evaluation and group to review available information approval of medicines to fight Ebola. Progress on Ebola experimental treatments – towards provision of treatments and vaccines is excluding convalescent therapies – and summarized below. invited developers to submit their data (5).

In August 2014, a WHO-convened panel Vaccines had agreed unanimously that is ethically On 29–30 September, 70 experts acceptable to use of experimental attended a WHO-convened consultation medicines and vaccines under the on Ebola vaccines. They took stock of the exceptional circumstances of the Ebola many ongoing efforts to rapidly evaluate epidemic (1). In early September, WHO the safety and efficacy of Ebola vaccines convened a consultation on potential for deployment as soon as possible to Ebola therapies and vaccines (2). The critical frontline workers and ultimately to importance of supportive care and populations at risk in mass vaccination community response was stressed in this campaigns. Two candidate vaccines have and subsequent discussions. clinical-grade vials available for safety trials. (6) Treatments In October, WHO convened industry In September, more than 200 experts leaders and key partners to discuss trials from around the world met at WHO and production of Ebola vaccine (7). and agreed to prioritize convalescent Consensus was achieved to make results blood and plasma therapies for further available in December 2014, to begin investigation. Many questions remain to efficacy trials at the same time, and to be answered about the safety and efficacy scale up production in 2015. of convalescent therapies, the feasibility of Also in October the EMA gave its first implementation in countries with shattered scientific advice on a development plan health systems, and the prospects of for an Ebola vaccine, using a new ‘rolling scaling up therapy to curb the fatality rate review’ procedure for data assessment (2). To support implementation, WHO has and sharing of outcomes with healthcare issued new interim guidance on the use of decision-makers in affected countries (8). convalescent therapies for national health At the time of writing, safety trials of authorities and blood transfusion services vaccines were underway in the U.S., U.K., (3). The first clinical trials of – possibly Mali and Switzerland, and about to begin

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in Gabon, Germany and Kenya.The two a diagnostic’s quality, safety and Swiss trials are coordinated by WHO, performance. (12) with testing done on healthy volunteers, some of whom will be deployed in the fight ►►(1) WHO Statement, 12 August 2014. against Ebola in West Africa (9). (2) WHO. Ebola situation assessment - 26 September 2014. At the meeting of the African Vaccine (3) WHO. Use of Convalescent Whole Regulatory Forum (AVAREF) in early Blood or Plasma Collected from Patients November, delegates discussed Recovered from Ebola Virus Disease for collaborative mechanisms to fast-track Transfusion, as an Empirical Treatment clinical trial approvals and registration of during Outbreaks. Version 1.0, September Ebola treatments and vaccines in affected 2014. (4) WHO. Ebola situation assessment, 6 countries, and – importantly – reaffirmed November 2014. the need to build stronger health systems (5) EMA Press release, 26 September 2014. (10). (6) WHO. Experimental Ebola vaccines. 1 October 2014. Supportive care (7) WHO News release, 24 October 2014. Industry leaders and key partners have (8) EMA Press release, 29 October 2014. (9) WHO News release, 6 November 2014. emphasized that community engagement (10) WHO Essential Medicines and Health remains key to fight Ebola and have Products. African regulators’ meeting called onlocal communities, national looking to expedite approval of vaccines and governments, NGOs and international therapies for Ebola [web page]. organizations to scale up concerted (11) Bah EI, Lamah M, Fletcher T, Jacob ST, Brett-Major DM, Sall AA et al. Clinical activities urgently. (7). Meanwhile, a Presentation of Patients with Ebola Virus WHO-coordinated retrospective study has Disease in Conakry, Guinea. N Engl J Med. shown that supportive care, especially 2014; 5 Nov 2014. rehydration and correction of metabolic (12) WHO. Ebola situation assessment - 18 abnormalities, may contribute to patient November 2014. survival (11).

Diagnostics Clinical trials transparency Quick and accurate diagnosis is key in fighting Ebola. WHO has launched two EMA adopts policy on publication urgent initiatives to accelerate the delivery of clinical reports of rapid, sensitive, safe and simple European Union – The EMA’s Ebola diagnostic tests to West African Management Board has unanimously countries. The first is a close collaboration adopted a new policy to publish the clinical of manufacturers, researchers, Médecins trial reports that underpin the decision- sans Frontières (MSF) staff, and the making on medicines. The policy will non-profit organization Foundation for enter into force on 1 January 2015 and Innovative New Diagnostics (FIND), will apply to clinical reports supporting and aims to support the development all applications for centralized marketing of suitable tests. The second is the authorizations submitted after that date. establishment of an emergency rapid According to the policy’s terms of use, review mechanism for assessing the reports cannot be used for commercial purposes. In the limited instances

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where they may contain commercially can apply some or all of its provisions with confidential information, this will be immediate effect. Two related guidelines redacted in accordance with the principles and procedural guidance are also being outlined in the policy’s annexes. updated. The new policy will serve as a ►►EMA Press release, 29 October 2014. complementary tool ahead of the implementation of the new EU Clinical Trials Regulation that will come into force EMA proposes harmonized clinical not before May 2016. Public access to trials plan for vaccine in children clinical reports will enable academics and European Union – The EMA has researchers to re-assess data sets, and proposed a single development plan will help to avoid duplication of clinical trial for new tetanus-diphtheria-acellular ►►EMA Press release, 2 October 2014. pertussis vaccines that all pharmaceutical companies across the EU should follow. The proposal aims to avoid the Pre-market assessment duplication of similar clinical trials and the unnecessary exposure of children to EMA revises guidance on clinical testing. biosimilars As the schedules of child vaccinations European Union – The EMA has vary slightly between EU countries, a published its revised guideline on large number of fairly similar clinical trials biosimilars. The main change is that are currently conducted in children when a developers can now use a comparator new vaccine is being developed. The EMA product authorized outside the European collaborated with the European Centre for Economic Area (EEA) in certain clinical Disease Prevention and Control (ECDC) studies and in non-clinical studies to define a single schedule for clinical conducted in vivo. This new concept trials. A panel of public health vaccinology aims to avoid unnecessary repetition experts have endorsed the proposal. of clinical trials. The comparator must The proposed plan has been released be authorized by a regulatory authority for a three-month public consultation. with similar rigorous scientific and ►►EMA News, 23 September 2014. regulatory standards to those of EMA, and the applicant must establish that the comparator is representative of the EMA pilot to seek patient views on reference medicine authorized in the EEA. medicines risks and benefits A biosimilar is a biological medicine European Union – The European that is similar to an already authorized Medicines Agency (EMA) has launched reference product (comparator). To obtain a pilot project to involve patients in the a marketing authorization the developer assessment of the benefits and risks of must demonstrate in studies that the medicines in its Committee for Medicinal biosimilar is as safe and effective as the Products for Human Use (CHMP). reference medicine, and meets the EMA’s Patients will be invited to present their quality requirements. views on medicines for which there is While the revised guideline will come an unmet medical need and where the into force as of 30 April 2015, applicants Committee has doubts on its regulatory

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decisions at any stage of the product life decisions for priority diseases. On the other cycle. EMA has published a document hand, regulation of IVDs is still very limited outlining the principles of this approach. or absent in many countries. Read more in WHO Drug Information Vol. 28, No. 3, 2014 The first active substance included in on what WHO is doing to bring quality- this pilot project has been afamelanotide, assured IVDs to its Member States. leading to the approval of a treatment for erythropoietic protoporphyria (EPP), a rare genetic blood disorder which causes Pharmacovigilance an absolute intolerance to light (see also page 466). Canada passes Vanessa’s Law The pilot project stems from a wider Canada – The Government of Canada EMA strategy to involve patients in the has passed modernized laws for drugs Agency’s activities. It will run for at least and medical devices. The Protecting one year, leading up to a proposal for full Canadians from Unsafe Drugs Act, implementation. known as “Vanessa’s Law”, will enable ►►EMA Press release, 26 September 2014. the Government to recall unsafe medicines, impose tough penalties, compel pharmaceutical companies to Australia to recognize EU make changes to products or do further conformity assessment for medical testing, require mandatory adverse events devices reporting by health care institutions, Australia – New regulations will allow and require transparency on regulatory Australian manufacturers to obtain market decisions. approval for most medical devices based The Act introduces the most profound on conformity assessment certification and important changes to the Food and from European notified bodies, the Drugs Act in its fifty years of existence. It accredited organizations that carry out is named after an Australian Member of product assessments in the EU. Parliament’s daughter who died of a heart The highest risk devices such as those attack while on a that containing medicines or tissues of animal, was later deemed unsafe and removed biological or microbial origin, or Class 4 from the market. in vitro diagnostics (IVDs) including ►►Government of Canada News release, HIV tests, will still need TGA conformity 6 November 2014. assessment. The respective regulatory amendments are expected to be in place later this year. EU project on using smartphones ►►Australian Assistant Minister for Health, for drug safety information Media release, 15 October 2014. European Union – The MHRA is leading a consortium of regulators, academics Editor’s note: As the above media release mentions, regulators commonly adapt the and the pharmaceutical industry in a level of control for IVDs to the level of risk three-year project, known as WEB- that product deficiencies would pose for RADR, to develop new ways of gathering public health. IVDs (including products information on suspected adverse drug like tuberculosis or malaria IVDs, which reactions (ADRs) using smartphones and are considered ‘low-risk’ in industrialized social media. WEB-RADR will help to countries) are crucial in guiding treatment

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develop recommendations on how these In 2013 only about 3% of adverse new tools should be used ethically and events reports received by the TGA scientifically alongside existing drug safety came from consumers. The new web site monitoring systems. is part of TGA’s activities taken in line The project is funded though the with an international trend for regulators Innovative Medicines Initiative, a public- to encourage reporting by consumers. private partnership between the European The TGA has also published a brochure Commission and the European Federation outlining what and how to report, and is of Pharmaceutical Industries and undertaking awareness activities and Associations (EFPIA). consumer research. (1) ►►MHRA Press release, 5 September 2014. Switzerland – With immediate effect, healthcare professionals and EMA expands public web access to pharmaceutical companies can report reports on suspected side effects suspected adverse drug reactions directly European Union – The EMA has added on the Internet through Swissmedic’s to its website information on suspected “ElViS” (Electronic Vigilance System) adverse drug reactions for an additional online reporting portal. Use of the portal 1 700 active substances contained in is subject to registration on the ElViS medicines approved in the European website, and companies are also required Union (EU) by national authorities. The to attend a Swissmedic training course. information comes directly from the Data protection and security satisfy the EudraVigilance database. The web site most stringent requirements. was launched in 2012 and initially only Swissmedic hopes that ElViS will result contained adverse events information for in more and better reports being received centrally authorized medicines. Over the nearer to the event, helping to improve next few years it will be expanded to cover drug and patient safety in Switzerland. (2) all medicines available in the EU. ►►(1) TGA News, 24 September 2014. Since July 2012 European (2) Swissmedic Announcement, 6 October pharmacovigilance legislation provides 2014. the possibility for patients to report side effects directly to the authorities in all EU Member States. Increasing numbers of New MHRA guidance on reporting patient reports are being received in the adverse drug reactions in children EudraVigilance database. United Kingdom – The MHRA has ►►EMA Press release, 6 October 2014. announced new simplified guidance on how healthcare professionals should report suspected adverse drug reactions Australia, Switzerland create web (ADRs) in children to its Yellow Card portals to report adverse reactions Scheme (mhra.gov.uk/yellowcard). Australia - The TGA has launched a Recognizing that it is impractical to new web-based service for consumers report all suspected ADRs in children, to report adverse events associated with the new guidance asks that healthcare medicines and vaccines. professionals report those reactions that are serious, medically significant or result

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in harm, and those that are associated Veterinary medicines with newer drugs and vaccines, identified by a black triangle symbol in the Yellow EU proposes veterinary medicines Card Scheme. The guidance also places legislation revisions greater importance on the reporting of European Union – The EMA has medication errors in children resulting welcomed a major revision of the legal in suspected ADRs, and explains the framework for veterinary medicines many reasons why monitoring of ADRs in in the EU proposed by the European children is particularly important. Commission. The revision includes ►►MHRA Press release, 25 September 2014. measures to fight the development of antimicrobial resistance, notably by restricting the veterinary use of certain Organizations antimicrobials that are reserved for the treatment of infections in people. It Australia and New Zealand to keep also proposes streamlined marketing separate regulatory authorities authorization procedures, simpler The Australian and New Zealand pharmacovigilance rules, better incentives Governments have agreed to cease for innovation, and clearer rules for efforts to establish a joint therapeutic internet retailing of veterinary medicines. products regulator, the Australia New Other EU institutions will now consider Zealand Therapeutic Products Agency the Commission’s proposals and will adopt (ANZTPA). The decision was taken after a their positions. review of progress and an assessment of ►►EMA News, 10 September 2014. the costs and benefits involved. The two countries will continue to co-operate on Sales of veterinary antibiotics in the regulation of therapeutic products. (1) Europe decrease The New Zealand authority has European Union – Sales of veterinary announced that work will now be antibiotics have decreased by 15% undertaken to strengthen the national according to the Fourth European regulatory scheme for therapeutic Surveillance of Veterinary Antimicrobial products. (2) Consumption (ESVAC) report. Increased ►►(1) Joint Media Release, 20 November awareness of the threat of antimicrobial 2014. resistance as well as national (2) Medsafe Media release, 20 November programmes, campaigns and restrictions 2014. have been cited among the reasons for the decrease. The ESVAC report is issued every year to inform antimicrobial policy and the responsible use of antimicrobials in EU Member States. ►►EMA Press release, 15 October 2014.

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Approved Benefits: New treatment option for patients with type 2 diabetes who cannot be

Netupitant and palonosetron: for managed with first-line regimens. Can be chemotherapy-induced nausea used alone or added to existing treatment Product name: Akynzeo® regimens. Class: Netupitant and palonosetron fixed- Safety information: Dulaglutide should dose combination; ATC code: A04AA55 not be used in patients with diabetic Approval: FDA ketoacidosis or those with severe stomach Use: Treatment of nausea and vomiting in or intestinal problems. As thyroid C-cell patients undergoing cancer chemotherapy. tumours have been observed in rodent Benefits: Added effectiveness in preventing studies, dulaglutide should not be used in vomiting episodes in the acute, delayed patients with a personal or family history of and overall phases after the start of medullary thyroid carcinoma (MTC), or in cancer chemotherapy, compared with oral patients with multiple endocrine neoplasia palonosetrone alone. syndrome type 2 (which predisposes them ►►FDA News release, 10 October 2014. to MTC). ►►FDA News release, 18 September 2014. ►►EMA /CHMP Summary of opinion, Naloxegol: for opioid-induced 25 September 2014. constipation Product name: Movantik® Class: Peripherally acting opioid receptor Antihaemophilic factor

antagonist; ATC code: A06AH03 (recombinant), porcine sequence : in Approval: FDA, EMA acquired haemophilia A Use: Oral treatment for opioid-induced Product name: Obizur® constipation in adults with chronic non- Class: Porcine coagulation factor VIII cancer pain. Approval: FDA (orphan drug designation) Benefits: Additional supportive care option to Use: Treatment of bleeding episodes decrease the constipating side effects of in adults with acquired hemophilia A opioids. (acquired factor VIII deficiency). Safety information: The FDA is requiring a Benefits: Porcine Factor VIII is similar postmarketing study to further evaluate enough to human Factor VIII to be the potential risk of cardiovascular adverse effective in blood clotting, but is less likely events. to be affected by the antibodies against ►►FDA News, 16 September 2014. human Factor VIII that are present in EMA /CHMP Summary of opinion, people with acquired haemophilia A. 25 September 2014. ►►FDA News release, 24 October 2014.

Dulaglutide: for type 2 diabetes Nonacog gamma : in haemophilia B Product name: Trulicity® Product name: Rixubis® Class: Glucagon-like -1 (GLP-1) Class: Antihaemorrhagic, blood coagulation receptor agonist factor IX; ATC code: B02BD04 Approval: FDA; EMA Approval: EMA Use: Once-weekly subcutaneous to Use: Treatment and prophylaxis of bleeding improve glycaemic control in adults with in patients with haemophilia B (congenital type 2 diabetes. factor IX deficiency) in patients of all age groups.

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Benefits: Ability to prevent and treat bleeds Class: Antiretroviral fixed-dose combination; in patients with haemophilia B including ATC code: J05AR14 during surgery. Use: Treatment of human immunodeficiency ►►EMA/CHMP Summary of opinion, 23 virus (HIV) in antiretroviral therapy October 2014. (ART)-naïve adults and ART-experienced adults with no darunavir (DRV) resistance associated mutations.

Afamelanotide: for erythropoietic Benefits: Ability to provide sustainable protoporphyria virological suppression if given in Product name: Scenesse® combination with other antiretroviral Class: Protective against UV radiation for medicinal products for treatment of HIV-1 systemic use; ATC code: D02BB02 infection. Approval: EMA (orphan designation) ►►EMA/CHMP Summary of opinion, Use: Prevention of phototoxicity in adults 25 September 2014. with erythropoietic protoporphyria (EPP), a rare genetic disease causing intolerance

to light. Ledipasvir & sofosbuvir: for hepatitis Benefits: Afamelanotide stimulates the C infection production of eumelanin, which naturally Product name: Harvoni® protects the skin against phototoxic Class: Fixed-dose combination of two direct- reactions caused by sunlight, thereby acting antivirals. Sofosbuvir is an NS5B significantly improving patients’ quality of inhibitor; ledipasvir – a new drug – is an life. NS5A inhibitor. ATC Code (temporary Safety information: The company will classification): J05AX65 implement a risk management plan and Approval: EMA (accelerated assessment), establish a registry of patients to collect FDA (priority review, breakthrough therapy safety and efficacy data. designation) Note: The approval was granted under Use: Treatment of chronic hepatitis C virus exceptional circumstances, despite infection in adults. a lack of robust efficacy data due to Benefits: High cure rates in patients with the difficulties to recruit patients for chronic HCV infection without the need placebo-controlled trials. Assessment for treatments involving interferons. The was supported by data from the use latter are associated with poor tolerability of the medicine in compassionate use and potentially serious side effects that programmes globally. In addition, the EMA rule out such treatment in a considerable Committee heard feedback from patients proportion of HCV patients. and healthcare professionals involved ►►EMA News, 26 September 2014. in an expert group. This was the first FDA News release, 10 October 2014. time that patients were involved in EMA discussions on the benefits and risks of a

medicine (see also page 461). Dasabuvir : for hepatitis C infection ►►EMA Press release, 24 October 2014. Product name: Exviera® Class: Antiviral agent, NS5B inhibitor. ATC code (temporary classification): J05AX16

Darunavir & cobicistat: for HIV Approval: EMA (accelerated assessment) infection Use: Treatment of chronic hepatitis C in Product name: Rezolsta® adults, in combination with other medicinal Approval: EMA products.

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Benefits: Ability to inhibit viral replication Pembrolizumab: for advanced in infected host cells which can lead to melanoma the eradication of the virus, correlating Product name: Keytruda® to a cure of chronic hepatitis C virus Class: Antineoplastic; PD-1 pathway blocker (HCV) infection, in both non-cirrhotic (first in class). ATC code (temporary and compensated cirrhotic patients with classification): L01XC18 genotype 1a/1b HCV infection. Approval: FDA (accelerated approval; ►►EMA/CHMP opinion, 20 November 2014. breakthrough therapy, orphan product, priority review) Use: Treatment of advanced or unresectable

Ombitasvir & paritaprevir & ritonavir: melanoma no longer responding to other for hepatitis C infection drugs (ipilimumab, or ipilimumab and a Product name: Viekirax® BRAF inhibitor in patients whose tumors Class: Fixed-dose combination of two express a BRAF V600 mutation) antiviral agents, inhibitors of NS5A Benefits: Substantial improvement over (ombitasvir) and NS3/4A (paritaprevir), existing therapies; shrinking tumours in with ritonavir as a pharmacokinetic approximately 24 percent of patients. enhancer. ATC code (temporary Improvement on survival remains to be classification): J05AX67 established. Approval: EMA (accelerated assessment) Safety information: Potential for severe Use: Treatment of chronic hepatitis C in immune-mediated side effects that can adults, in combination with other medicinal involve healthy organs, including the products . lung, colon, hormone-producing glands Benefits: Ability to inhibit viral replication and liver. In safety studies, such effects in infected host cells which can lead to occurred uncommonly. the eradication of the virus, correlating ►►FDA News release, 4 September 2014. to a cure of chronic hepatitis C virus (HCV) infection, in both non-cirrhotic

and compensated cirrhotic patients with Ramucirumab : for gastric cancer genotype 1a/1b and 4 HCV infection. Product name: Cyramza® ►►EMA/CHMP opinion, 20 November 2014. Class: Human receptor-targeted antibody that specifically binds VEGF Receptor 2 and blocks angiogenesis by binding of Meningococcus B vaccine VEGF-A, VEGF-C, and VEGF-D. Product name: Trumenba® Approval: EMA (orphan designation) Class: Meningococcal Group B vaccine; Use: Treatment of adult patients with ATC code: J07AH09 advanced gastric cancer or gastro- Approval: FDA (accelerated approval, oesophageal junction adenocarcinoma breakthrough therapy) with disease progression after Use: Prevention of invasive meningococcal prior platinum and fluoropyrimidine disease caused by Neisseria meningitidis chemotherapy. Ramucirumab can be serogroup B in individuals 10–25 years of used in combination with paclitaxel, or age. as monotherapy in patients for whom Benefits: First licenced meningococcal treatment in combination with paclitaxel is group B vaccine in the U.S.; in addition to not appropriate. licenced vaccines for serogroups A, C, Y Benefits: Ability to improve the survival and W. in patients compared to chemotherapy ►►FDA News release, 29 October 2014. alone (when used in combination with

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chemotherapy) and compared to placebo Nintedanib: for non-small cell lung (when used alone). cancer / idiopathic pulmonary ►►EMA/CHMP Summary of opinion, fibrosis 25 September 2014. Product name: EU: Vargatef®, Ofev®; U.S.: Ofev® Class: Tyrosine kinase inhibitor anti-

Secukinumab: for plaque psoriasis neoplastic agent, angiogenesis inhibitor. Product name: Cosentyx® ATC code (temporary classification): Class: Immunosuppressant; ATC code: L01XE31 L04AC10 Approval: EMA (orphan designation for Approval: EMA Ofev®), FDA (fast track, priority review, Use: Treatment of moderate to severe plaque orphan product, and breakthrough psoriasis in adults who are candidates for designations) systemic therapy Use:Vargatef®: In combination with docetaxel, Benefits: More efficacious than placebo with treatment of locally advanced, metastatic respect to two co-primary endpoints in or locally recurrent non-small cell lung clinical studies. cancer of adenocarcinoma tumour ►►EMA/CHMP opinion, 20 November 2014. histology after first-line chemotherapy. Ofev®: Treatment of idiopathic pulmonary fibrosis.

Pirfenidone: for idiopathic pulmonary Benefits: Vargatef®: Improvement in fibrosis progression-free survival and overall Product name: Esbriet® survival compared to docetaxel plus Class: Immunosuppressant; ATC code: placebo. L04AX05 Ofev®: Additional treatment option for Approval: FDA (fast track, priority review, patients with idiopathic pulmonary fibrosis. orphan product, and breakthrough Safety information: Not recommended for designations). patients with moderate to severe liver Use: Treatment of idiopathic pulmonary problems. Can cause birth defects or fibrosis death to an unborn baby; women who are Benefits: Additional treatment option for able to get pregnant should use adequate patients with idiopathic pulmonary fibrosis, contraception during and for at least three a serious, chronic condition. Current months after the last dose of treatment. treatments include oxygen therapy, ►►EMA/CHMP Summary of opinion, pulmonary rehabilitation, and lung 25 September 2014. transplant. EMA/CHMP Opinion, 20 November 2014. : The FDA also approved nintedanib for Notes FDA News release, 15 October 2014. the same use, see below. Pirfenidone was approved by EMA in 2011

under orphan designation. Olaparib: for a subtype of ovarian Safety information: Not recommended for cancer patients who have severe liver problems, Product name: Lynparza® end-stage kidney disease, or who require Class: Poly ADP ribose polymerase (PARP) dialysis. Patients should minimize inhibitor (first-in-class) exposure to sunlight, as pirfenidone may Approval: EMA (orphan designation) cause them to sunburn more easily. Use: Monotherapy for the maintenance ►►FDA News release, 10 October 2014. treatment of adult patients with relapsed, platinum‑sensitive epithelial ovarian,

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fallopian tube or primary peritoneal cancer Use: To treat pain severe enough to require carrying a BRCA gene mutation, and daily, around-the-clock, long-term opioid who have responded to platinum-based treatment and for which alternative chemotherapy. treatment options are inadequate. Benefits: Targetted treatment of a subtype of Benefits: The formulation is expected to ovarian cancer for which limited treatment reduce abuse by ingestion, snorting or options are available. injection. ►►EMA Press release, 24 October 2014. Safety information: The product can still be abused or misused, and can then cause an overdose that may result in death.

Blinatumomab: for a rare form of Additional postmarketing studies will be acute lymphoblastic leukaemia conducted to assess the effects of the Product name: Blincyto® abuse-deterrent features on the risk for Class: Immunotherapeutic monoclonal abuse, and the consequences of that antibody, T-cell engager abuse in the community. Approval: FDA (breakthrough therapy Note: This is the fourth extended-release designation, priority review and orphan opioid analgesic to be approved by the product designation) FDA with labelling consistent with the Use: Treatment of relapsed or refractory FDA’s 2013 draft guidance on evaluation Philadelphia chromosome-negative and labelling of abuse-deterrent opioids precursor B-cell acute lymphoblastic (after OxyContin®, Targiniq® and leukaemia. Embeda®). Benefits: Potential for substantial ►►FDA News release, 20 November 2014. improvement over available therapies. See also: Guidance for Industry. Abuse- The manufacturer is required to conduct Deterrent Opioids — Evaluation and a study to verify that the drug improves Labeling. Draft Guidance. FDA; 2013. survival. Safety information: Boxed warning about the risks of low blood pressure and difficulty Labelling changes approved breathing (cytokine release syndrome)

at the start of the first treatment, difficulty : for Cushing’s with thinking (encephalopathy) and other syndrome nervous system side effects. The medicine Product name: Ketoconazole HRA® was approved with a Risk Evaluation Class: Antimycotic for systemic use; ATC and Mitigation Strategy, which consists code: J02AB02 of a communication plan to inform health Approval: EMA (orphan designation; care providers about the serious risks accelerated approval of new indication) and the potential for preparation and Use: Treatment of Cushing’s syndrome administration errors. Benefits: Additional treatment option when ►►FDA News release, 3 December 2014. surgery or other medicines fail or cannot be administered. Note: Ketoconazole has been used “off-label”

Abuse-deterrent hydrocodone: single- for more than 30 years to treat this rare

entity, extended release product; and potentially life-threatening condition, Product name: Hysingla ER® although it has never been authorized for Class: Opioid analgesic this indication in the EU. Approval: FDA (in line with guidance on Safety information: In July 2013, EMA abuse-deterrent properties) recommended to suspend the marketing

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authorizations of oral ketoconazole unprotected intercourse or contraceptive medicines to treat fungal infections due failure; works best if taken within 24 hours. to the risk of liver injury. In the treatment Benefits: Making the medicine available of Cushing’s syndrome however, the without prescription in the EU should benefits are greater than the risks, which speed up women’s access to the medicine can be managed by close monitoring of and therefore increase its effectiveness. the patients’ liver function. The product is Safety information: The safety profile to be prescribed only by specialists as the of ulipristal is comparable to that of posology needs to be individualized for levonorgestrel-containing emergency each patient. Relevant information will be contraceptives, which are already sent to healthcare professionals in the EU. available without prescription in most EU ►►EMA Press release, 26 September 2014. countries and are registered for use up to 72 hours after unprotected intercourse or contraceptive failure.

Ulipristal: emergency contraceptive Notes: If granted by the European without prescription; Commission, the re-classification to non- Product name: ellaOne® prescription status would in principle need Class: Emergency contraceptive; ATC code: to be implemented by all EU Member G03AD02 States. Any exception regarding the Approval: EMA/CHMP recommendation, to non-prescription status of this medicine be sent to the European Commission for a would fall within the responsibilities of the legally binding decision. Member States. Use: To prevent unintended pregnancy. Must ►►EMA Press release, 21 November 2014. be taken within 120 hours (five days) of

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