Nomegestrol acetate/Estradiol

12 new medicines recommended for approval EMA’s human medicines committee ( CHMP ) recommended 12 medicines for approval at its September 2022 meeting. The CHMP recommended granting a marketing authorisation for Beyfortus (nirsevimab) intended for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in newborns and infants during their first RSV season (when there is a risk of RSV infection in the community). Beyfortus was supported through EMA's PRIority MEdicines (PRIME) scheme, which provides early and enhanced scientific and regulatory support to medicines that have a particular potential to address patients' unmet medical needs. See more information in the news announcement in the grid below. The committee adopted a positive opinion for Enjaymo * (sutimlimab) for the treatment of haemolytic anaemia (breakdown of red blood cells) in adult patients with cold agglutinin disease, a rare autoimmune disorder characterised by the premature destruction of red blood cells. Livtencity * (maribavir) received a positive opinion for the treatment of adults and paediatric patients with cytomegalovirus infection and/or disease that is refractory to one or more prior therapies. Cytomegalovirus is a type of herpes virus that commonly causes infection after a stem cell or an organ transplant. The committee adopted a positive opinion for Melatonin Neurim (melatonin) for the treatment of insomnia, a sleeping disorder affecting more than 10% of the European Union (EU) population. The CHMP gave a positive opinion for Mycapssa * (octreotide) for the treatment of acromegaly, a rare hormonal disorder where the body produces too much growth hormone. This causes body tissues and bones to grow more quickly, leading e.g. to the enlargement of the hands, feet, forehead, jaw or nose. The committee recommended granting a conditional marketing authorisation for Pyrukynd * (mitapivat) for the treatment of an inherited condition called pyruvate kinase deficiency, a rare genetic disorder characterised by the premature destruction of red blood cells. Zynlonta * (loncastuximab tesirine) received a positive opinion from the CHMP . This medicine is intended for the treatment of adult patients with diffuse large B-cell lymphoma and high-grade B-cell lymphoma, two types of cancer that begin in the lymphatic system when abnormal white blood cells grow. The committee adopted a positive opinion for the biosimilar medicine Ximluci (ranibizumab) for the treatment of neovascular age-related macular degeneration, a progressive retinal macular disease, causing gradual vision impairment, mainly in the elderly population. The CHMP recommended granting a marketing authorisation for Teriparatide SUN (teriparatide) for the treatment of osteoporosis in adults. Osteoporosis affects around 22% of women over the age of 50 in the EU. The recommendation followed a hybrid application, which relies in part on the results of pre-clinical tests and clinical trials of an already authorised reference product and in part on new data. The CHMP gave a positive opinion for the generic medicine Sorafenib Accord (sorafenib) for the treatment of hepatocellular carcinoma and renal cell carcinoma, two cancers that start in cells or tissues of the liver and kidney. The committee adopted a positive opinion for the generic medicines Teriflunomide Accord and Teriflunomide Mylan (teriflunomide), indicated for the treatment of multiple sclerosis, a chronic disease affecting the central nervous system. Recommendations on extensions of therapeutic indication for 11 medicines The committee recommended 12 extensions of indication for medicines that are already authorised in the EU: Adtralza , Biktarvy , Brukinsa , Evusheld , Exparel liposomal, Revolade, Skyrizi , Vaxneuvance , Veklury (includes two extensions of indication for two paediatric populations, see the COVID-19 update below), Xalkori and Yescarta . Withdrawals of initial applications The application for marketing authorisation for Exkivity was withdrawn by the respective applicant. This medicine was indicated for the treatment of a certain type of lung cancer. A question-and-answer document on the withdrawal is available in the grid below. The application for marketing authorisation for Sevsury was withdrawn by the respective applicant. This medicine was indicated for the treatment of progressive neuroendocrine tumours. A question-and-answer document on the withdrawal is available in the grid below. Re-examination concluded The CHMP confirmed its recommendation to suspend the marketing authorisations of several generic medicines tested by Synchron Research Services , a contract research organisation (CRO) located in Ahmedabad, India. This concludes the re-examination requested by the marketing authorisation holders for some of the medicines concerned. For more information, see the public health communication in the grid below. COVID-19 update Since the CHMP meeting in July, several recommendations related to COVID-19 vaccines and therapeutics were made. Authorising use of Nuvaxovid as a booster dose for adults who have had Nuvaxovid, an mRNA vaccine or an adenoviral vector vaccine as their primary vaccination. (The recommendation was made on 1 September 2022) Authorising two vaccines adapted to provide broader protection against COVID-19. Comirnaty Original/Omicron BA.1 and Spikevax bivalent Original/Omicron BA.1 are for use in people aged 12 years and above who have received at least primary vaccination against COVID-19. For more information, see the news announcement . (The recommendation was made on 1 September 2022) COVID-19 recommendations adopted during the present meeting of the CHMP : Authorising the adapted bivalent vaccine Comirnaty Original/Omicron BA.4-5 for use in people aged 12 years and above who have received at least a primary course of vaccination against COVID-19. This vaccine is an adapted version of the mRNA COVID-19 vaccine Comirnaty and targets the Omicron subvariants BA.4 and BA.5 in addition to the original strain of SARS-CoV-2. For more information, see the news announcement . Converting the conditional marketing authorisations of the COVID-19 vaccines Comirnaty and Spikevax into standard marketing authorisations . CHMP considered that the additional studies conducted by the companies as part of their post-authorisation obligations have provided ample information on the vaccines’ protection against COVID-19, as well as their quality and safety. For more information, see the news announcement . Approving a new manufacturing site in Dessau-Rosslau, Germany, for COVID-19 Vaccine Valneva . Authorising booster doses of Comirnaty for children from 5 to 11 years of age . Extending the use of COVID-19 therapeutic Evusheld for the treatment of adults and adolescents with COVID-19 who do not require supplemental oxygen. Extending the use of COVID-19 therapeutic Veklury in two paediatric populations: Paediatric patients (of at least 4 weeks of age and weighing at least 3 kg) with pneumonia requiring supplemental oxygen or other non-invasive ventilation at the start of treatment. Paediatric patients (weighing at least 40 kg) who do not require supplemental oxygen and who are at increased risk of progressing to severe COVID-19. Safety update At its extraordinary meeting, on 2 September 2022, the CHMP endorsed the recommendation of the Pharmacovigilance Risk Assessment Committee ( PRAC ) and recommended that medicines containing high-dose nomegestrol (3.75 – 5 mg) or high-dose chlormadinone (5 – 10 mg) should be used at the lowest effective dose and for the shortest duration possible, and only when other interventions are not appropriate. In addition, low- and high-dose nomegestrol- or chlormadinone-containing medicines must not be used by patients who have, or have had, meningioma. For more information, see the news announcement . Agenda and minutes The agenda of the September 2022 CHMP meeting is published on EMA's website. Minutes of the September 2022 CHMP meeting will be published in the coming weeks. CHMP statistics Key figures from the September 2022 CHMP meeting are represented in the graphic below. *This product was designated as an orphan medicine during its development. Orphan designations are reviewed by EMA's Committee for Orphan Medicinal Products ( COMP ) at the time of approval to determine whether the information available to date allows maintaining the medicine’s orphan status and granting the medicine ten years of market exclusivity . Positive recommendations on new medicines Name of medicine Beyfortus International non-proprietary name (INN) nirsevimab Marketing-authorisation applicant AstraZeneca AB Therapeutic indication Prevention of respiratory syncytial virus lower respiratory tract disease in newborns and infants More information Beyfortus: Pending EC decision News announcement: New medicine to protect babies and infants from respiratory syncytial virus (RSV) infection Name of medicine Enjaymo INN sutimlimab Marketing-authorisation applicant Genzyme Europe BV Therapeutic indication Treatment of haemolytic anaemia in adult patients with cold agglutinin disease More information Enjaymo: Pending EC decision Name of medicine Livtencity INN maribavir Marketing-authorisation applicant Takeda Pharmaceuticals International AG Ireland Branch Therapeutic indication Treatment of cytomegalovirus infection and/or disease that is refractory to one or more prior therapies More information Livtencity: Pending EC decision Name of medicine Melatonin Neurim INN melatonin Marketing-authorisation applicant RAD Neurim Pharmaceuticals EEC SARL Therapeutic indication Treatment of insomnia More information Melatonin Neurim: Pending EC decision Name of medicine Mycapssa INN octreotide Marketing-authorisation applicant Amryt Pharmaceuticals DAC Therapeutic indication Treatment of acromegaly More information Mycapssa: Pending EC decision Name of medicine Pyrukynd INN mitapivat Marketing-authorisation applicant Agios Netherlands B.V. Therapeutic indication Treatment of pyruvate kinase deficiency More information Pyrukynd: Pending EC decision Name of medicine Zynlonta INN loncastuximab tesirine Marketing-authorisation holder ADC Therapeutics (NL) B.V. Therapeutic indication Treatment of adult patients with diffuse large B-cell lymphoma and high-grade B-cell lymphoma More information Zynlonta: Pending EC decision Positive recommendation on new biosimilar medicine Name of medicine Ximluci INN ranibizumab Marketing-authorisation applicant STADA Arzneimittel AG Therapeutic indication Treatment of neovascular age-related macular degeneration More information Ximluci: Pending EC decision Positive recommendation on new hybrid medicine Name of medicine Teriparatide SUN INN teriparatide Marketing-authorisation applicant Sun Pharmaceutical Industries Europe B.V. Therapeutic indication Treatment of osteoporosis in adults More information Teriparatide SUN: Pending EC decision Positive recommendations on new generic medicines Name of medicine Sorafenib Accord INN sorafenib Marketing-authorisation applicant Accord Healthcare S.L.U. Therapeutic indication Treatment of hepatocellular carcinoma and renal cell carcinoma More information Sorafenib Accord: Pending EC decision Name of medicine Teriflunomide Accord INN teriflunomide Marketing-authorisation applicant Accord Healthcare S.L.U. Therapeutic indication Treatment of multiple sclerosis More information Teriflunomide Accord: Pending EC decision Name of medicine Teriflunomide Mylan INN teriflunomide Marketing-authorisation applicant Mylan Pharmaceuticals Limited Therapeutic indication Treatment of multiple sclerosis More information To be published shortly Positive recommendations on extensions of indications Name of medicine Adtralza INN tralokinumab Marketing-authorisation holder LEO Pharma A/S More information Adtralza: Pending EC decision Name of medicine Biktarvy INN bictegravir / emtricitabine / tenofovir alafenamide Marketing-authorisation holder Gilead Sciences Ireland UC More information Biktarvy: Pending EC decision Name of medicine Brukinsa INN zanubrutinib Marketing-authorisation holder BeiGene Ireland Ltd More information Brukinsa: Pending EC decision Name of medicine Evusheld INN tixagevimab / cilgavimab Marketing-authorisation holder AstraZeneca AB More information Evusheld: Pending EC decision Name of medicine Exparel liposomal INN bupivacaine Marketing-authorisation holder Pacira Ireland Limited More information Exparel liposomal: Pending EC decision Name of medicine Revolade INN eltrombopag Marketing-authorisation holder Novartis Europharm Limited More information Revolade: Pending EC decision Name of medicine Skyrizi INN risankizumab Marketing-authorisation holder AbbVie Deutschland GmbH & Co. KG More information Skyrizi: Pending EC decision Name of medicine Vaxneuvance Common name pneumococcal polysaccharide conjugate vaccine (adsorbed) Marketing-authorisation holder Merck Sharp & Dohme B.V. More information Vaxneuvance: Pending EC decision Name of medicine Veklury INN remdesivir Marketing-authorisation holder Gilead Sciences Ireland UC More information Veklury: Pending EC decision Name of medicine Xalkori INN crizotinib Marketing-authorisation holder Pfizer Europe MA EEIG More information Xalkori: Pending EC decision Name of medicine Yescarta INN axicabtagene ciloleucel Marketing-authorisation holder Kite Pharma EU B.V. More information Yescarta: Pending EC decision Withdrawals of initial marketing authorisation applications Name of medicine Exkivity INN mobocertinib Marketing-authorisationapplicant Takeda Pharma A/S More information Exkivity: Withdrawn application Name of medicine Sevsury INN surufatinib Marketing-authorisationapplicant Hutchmed Europe B.V. More information Sevsury: Withdrawn application Outcome of referral re-examination Name of medicine Synchron Research Services More information Synchron Other updates List item Scientific advice and protocol assistance adopted during the CHMP meeting 12-15 September 2022 (PDF/230.36 KB) (new) Adopted First published: 16/09/2022 EMA/CHMP/SAWP/769857/2022

EMA’s human medicines committee ( CHMP ) has endorsed the recommendation of the Pharmacovigilance Risk Assessment Committee ( PRAC ), which concluded that the benefits of medicines containing nomegestrol or chlormadinone outweigh the risks, provided new measures are taken to minimise the risk of meningioma . A meningioma is a tumour of the membranes covering the brain and spinal cord. It is usually benign and is not considered to be a cancer, but due to their location in and around the brain and spinal cord meningiomas can in rare cases cause serious problems. The CHMP has recommended that medicines containing high-dose nomegestrol (3.75 – 5 mg) or high-dose chlormadinone (5 – 10 mg) should be used at the lowest effective dose and for the shortest duration possible, and only when other interventions are not appropriate. In addition, low- and high-dose nomegestrol- or chlormadinone-containing medicines must not be used by patients who have, or have had, meningioma. As well as restricting the use of the high-dose medicines, the CHMP has recommended that patients should be monitored for symptoms of meningioma, which can include change in vision, hearing loss or ringing in the ears, loss of smell, headaches, memory loss, seizures and weakness in arms or legs. If a patient is diagnosed with meningioma, treatment with these medicines must be permanently stopped. The product information for the high-dose medicines will also be updated to include meningioma as a rare side effect. The recommendations follow a review by the PRAC of available data, including post-marketing safety data and results from two recent epidemiological studies. 1’2 These data showed that the risk of meningioma increases with increasing dose and duration of treatment. The CHMP endorsed the PRAC ’s assessment of this risk. The CHMP opinion has been sent to the European Commission, which will issue a legally binding decision valid across the EU. Information for patients Meningiomas have been reported with the use of nomegestrol- or chlormadinone-containing medicines. This risk, which is very low, is increased when the medicines are used at high doses (3.75 - 5 mg for nomegestrol and 5 - 10 mg for chlormadinone) and for prolonged periods of time. EMA is therefore recommending that these medicines should only be used at the lowest effective dose and for the shortest duration possible. Higher doses (3.75 – 5 mg nomegestrol and 5 - 10 mg chlormadinone) should only be considered if other interventions are not possible. You should not use or be prescribed nomegestrol- or chlormadinone-containing medicines if you have a meningioma or have had one in the past. Contact your doctor immediately if you experience a change in vision (seeing double or blurriness), hearing loss or ringing in the ears, loss of smell, headaches that worsen with time, memory loss, seizures and weakness in your arms or legs. If you are diagnosed with a meningioma while using a nomegestrol- or chlormadinone-containing medicine, your doctor will stop your treatment with the medicine. The risk of meningioma may decrease after you stop treatment with a nomegestrol- or chlormadinone-containing medicine. Information for healthcare professionals Meningiomas (single and multiple) have been reported with the use of nomegestrol- or chlormadinone-containing medicines, particularly at high doses and for prolonged time. The risk increases with increasing cumulative doses. The use of these medicines at high doses should be restricted to situations where other interventions are considered inappropriate, and they should be used at the lowest effective dose and for the shortest duration. Nomegestrol- or chlormadinone-containing medicines are contraindicated in patients with meningioma or a history of meningioma. Patients should be monitored for signs and symptoms of meningiomas in line with clinical practice. If a patient is diagnosed with meningioma, treatment with these medicines should be permanently stopped. Available evidence suggests that the risk of meningioma decreases after treatment discontinuation of the nomegestrol- or chlormadinone-containing medicine. A direct healthcare professional communication (DHPC) will be sent in due course to healthcare professionals prescribing, dispensing or administering the medicine. The DHPC will also be published on a dedicated page on the EMA website. More about the medicine Medicines containing nomegestrol acetate or chlormadinone acetate are available as tablets to be taken by mouth. They are available on their own or in combination with oestrogens to treat gynaecological disorders such as amenorrhoea (absence of menstrual periods) and other menstrual disorders, uterine bleeding, endometriosis (a condition in which tissue similar to the lining of the womb grows elsewhere in the body), breast tenderness, and as hormone replacement therapy or contraceptives (birth control). The medicines are marketed under several trade names including Belara, Lutenyl, Luteran, Naemis and Zoely and as generic medicines . With the exception of Zoely (nomegestrol acetate/estradiol), which is centrally authorised, all medicines reviewed during this procedure have been authorised via national procedures. Warnings about the risk of meningioma are already included in the product information for some of them, although the wording may differ across EU Member States. The CHMP recommendation will lead to alignment of the product information for these medicines across the EU. More about the procedure The review of products containing nomegestrol or chlormadinone was initiated at the request of France, under Article 31 of Directive 2001/83/EC . The review was first carried out by the PRAC , the Committee responsible for the evaluation of safety issues for human medicines, which made a set of recommendations. The PRAC recommendations were sent to the CHMP , responsible for questions concerning medicines for human use, which adopted the Agency’s opinion. The CHMP ’s opinion will now be forwarded to the European Commission, which will issue a final legally binding decision applicable in all EU Member States in due course. 1 Nguyen P, Hoisnard L, Neumann A, Zureik M, Weill A. Utilisation prolongée de l’acétate de chlormadinone et risque de méningiome intracrânien: une étude de cohorte à partir des données du SND. EPI-PHARE , 2021. 2 Nguyen P, Hoisnard L, Neumann A, Zureik M, Weill A. Utilisation prolongée de l’acétate de nomégestrol et risque de méningiome intracrânien: une étude de cohorte à partir des données du SNDS. EPI-PHARE , 2021.