CHAPTER 1: KEY ACHIEVEMENTS IN 2023
Human medicines
Medicines recommended for approval
Authorisation of new medicines is essential to advancing public health as they bring new treatment opportunities for patients. In 2023, EMA recommended 77 medicines for marketing authorisation, 39 of which had a new active substance. Many of these represented significant progress in their therapeutic areas, including:
Abrysvo, a vaccine to protect small infants, via immunisation of the mother during pregnancy, and adults from the age of 60 and older people against lower respiratory tract disease caused by respiratory syncytial virus (RSV). RSV is a common respiratory virus that usually causes mild, cold-like symptoms that can be serious in vulnerable people, including older adults and those with lung or heart disease and diabetes.
Aqumeldi, for the treatment of heart failure in children from birth to less than 18 years.
Arexvy, a vaccine for active immunisation of adults aged 60 years and older against lower respiratory tract disease caused by respiratory syncytial virus (RSV).
Camzyos, for the treatment of symptomatic obstructive hypertrophic cardiomyopathy, a disease in which the heart muscle becomes thickened and can make it harder for the heart to pump blood.
Casgevy, for the treatment of transfusion dependent beta-thalassemia and severe sickle cell disease, two inherited rare diseases caused by genetic mutations that affect the production or function of haemoglobin, the protein found in red blood cells that carries oxygen around the body. This is the first medicine using CRISPR/Cas9, a novel gene-editing technology.
Columvi, for the treatment of diffuse large B-cell lymphoma, an aggressive type of non-Hodgkin lymphoma, a cancer of the lymphatic system that can arise in lymph nodes or outside of the lymphatic system.
Elrexfio, for the treatment of adult patients with relapsed or refractory multiple myeloma, a rare cancer of the bone marrow that affects plasma cells, a type of white blood cell that produces antibodies.
Finlee, in combination with Spexotras, for the treatment of paediatric patients aged one year and older with glioma, a type of brain tumour that begins in glial cells, the cells that surround and support nerve cells.
Jaypirca, for the treatment of relapsed or refractory mantle cell lymphoma which develops when B-cells, a type of white blood cell that makes antibodies, become abnormal.
Krazati, for the treatment of adults with advanced non-small cell lung cancer with a G12C mutation in the KRAS gene whose disease has worsened after at least one systemic treatment.
Loargys, treatment of hyperargininaemia, a rare disease with neurological clinical signs including spasticity, ataxia, hyperreflexia, incoordination, and seizures.
Lytgobi, for the treatment of cholangiocarcinoma or bile duct cancer, a type of cancer that forms in the slender tubes that carry the digestive fluid.
Omjjara, the first treatment for myelofibrosis, a rare blood cancer that affects the bone marrow, in patients with moderate-to-severe anaemia.
Pedmarqsi, for the prevention of ototoxicity induced by cisplatin chemotherapy in children from one month up to 18 years of age with localised, non-metastatic, solid tumours. Ototoxicity is the development of hearing or balance problems due to a medicine.
Skyclarys, for the treatment of Friedreich’s ataxia, an inherited disease causing a range of symptoms that worsen over time, including difficulty walking, inability to co-ordinate movements, muscle weakness, speech problems, damage to the heart muscle and diabetes.
Talvey, for the treatment of adult patients with relapsed and refractory multiple myeloma, a rare cancer of the bone marrow that affects plasma cells, a type of white blood cell that produces antibodies.
Tepkinly, for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma, a fast-growing cancer of the lymphatic system.
Early access to medicines that address public health needs
In 2023, three medicines received a recommendation for marketing authorisation following an accelerated assessment: Abrysvo, Arexvy and Talvey. This mechanism is reserved for medicines that address unmet medical needs. It allows for faster assessment of eligible medicines by EMA’s scientific committees (within a maximum of 150 days rather than 210 days).
Eight medicines received a recommendation for a conditional marketing authorisation, one of the possibilities in the EU to give patients early access to new medicines: Casgevy, Columvi, Elrexfio, Jaypirca, Krazati, Lytgobi, Talvey and Tepkinly.
The conditional authorisation allows for early approval on the basis of less complete clinical data than normally required because the benefits of earlier patient access outweigh the potential risks of limited data. These authorisations are subject to specific post-authorisation obligations to generate complete data on the medicines.
One medicine (Loargys) was authorised under exceptional circ*mstances, a route that allows patients access to medicines that cannot be approved under a standard authorisation as comprehensive data cannot be obtained, either because there are only very few patients with the disease, or the collection of complete information on the efficacy and safety of the medicine would be unethical. These medicines are subject to specific post-authorisation obligations and monitoring.
The enhanced development support provided by EMA’s PRIority Medicines (PRIME) aims to help patients benefit as early as possible from promising medicines that target an unmet medical need. This is done by optimising the generation of robust data and enabling accelerated assessment. This year, three medicines with PRIME designation were recommended for approval (Casgevy, Elrexfio and Talvey).
Eighteen medicines under development were accepted in the scheme in 2023: endocrinology-gynaecology-fertility-metabolism (4), cardiovascular diseases (3), oncology (3), ophthalmology (3), vaccines for infectious diseases (2), gastroenterology – hepatology (1), neurology (1) and other, congenital, familialand genetic disorders (1).
Medicines for rare diseases
The EU framework for orphan medicines aims to encourage the development and marketing of medicines for patients with rare diseases by providing incentives for developers.
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 for maintaining the medicine's orphan status and granting the medicine ten years of market exclusivity. Among the 77 medicines recommended for marketing authorisation in 2023, 17 had an orphan designation that was confirmed by the end of the year.
Eight medicines lost their orphan status before receiving a marketing authorisation, which means they were still authorised as medicinal products, but not as orphan medicinal products, and thus no longer benefit from the incentives. These are: Elfabrio, Elrexfio, Inaqovi, Jaypirqa, Lytgobi, Pombiliti, Vanflyta and Zilbrysq.
Medicines for children
Two medicines, Aqumeldi and Pedmarqsi, received a paediatric use marketing authorisation (PUMA), a process established in 2007 as part of the EU paediatric regulation intended to make it more profitable for pharmaceutical companies to develop and market medicines for children.
EMA issued a recommendation for Arpraziquantel, a new treatment option for the estimated 50 million young children with schistosomiasis, a neglected tropical disease caused by parasitic blood worms. Arpraziquantel was assessed under a regulatory procedure known as EU-Medicines for all (EU-M4All) that enables EMA, in cooperation with the World Health Organization, to support global regulatory capacity building and contribute to the protection and promotion of public health beyond the EU.
In addition, half of the extensions of indication that received a positive recommendation were for paediatric use. Extensions of indication included:
Soliris, for the treatment of paediatric patients from 6 years of age with refractory generalised myasthenia gravis.
Spexotras, for the treatment of children aged 1 year and older with high grade and low grade glioma, having a specific mutation (V600E) in the BRAF gene. It is used together with another cancer medicine, dabrafenib.
Bezlotoxumab, for the treatment of paediatric patients from 1 to 18 years of age with Clostridioides difficile infection (CDI).
New uses for existing medicines
In 2023, 77 extensions of indication were recommended. The extension of the use of a medicine that is already authorised for marketing in the EU can also offer new treatment opportunities for patients.
Over 65 % of all applicants that were granted a positive opinion for their medicine had received scientific advice or protocol assistance from EMA during their product’s development phase. The figure increases to 88 % for applicants for medicines with new active substances. Early engagement with developers allows EMA to clarify what kind of evidence is required to later evaluate a medicine for authorisation. This encourages generation of more robust data for regulatory assessment and thus protects patients from taking part in unnecessary or poorly designed clinical trials.
Negative opinions
The Committee for Medical Products for Human Use (CHMP) adopted a negative opinion for three medicines in 2023: Albrioza, Lagevrio and Sohonos.
94 % of all opinions (positive and negative) were reached by consensus among the CHMP members, which means that, following in-depth discussions, the experts agreed on all aspects of the marketing authorisations and there were no divergent opinions.
Keeping patients safe
Monitoring medicines after their authorisation – Optimising safe and effective use
Once a medicine has been authorised, EMA and the EU Member States continuously monitor the quality, safety and the benefit-risk balance of the medicine used in real life on the market. This is to optimise how the medicine is used by patients to achieve its full benefit and to protect patients from avoidable side effects. Regulatory measures range from a change in the product information, the suspension or withdrawal of a medicine, to the recall of a limited number of batches.
The product information for 387 centrally authorised medicines was updated on the basis of new safety data in 2023. Every year, PRAC recommendations on safety warnings are also included in the product information of many thousands of nationally authorised products (NAPs). The revised information is expected to help patients and healthcare professionals to make informed decisions when using or prescribing a specific medicine.
Important new advice issued in 2023 included:
- Adakveo (crizanlizumab), recommendation to no longer use Adakveo to prevent painful crises in patients aged 16 years and older with sickle cell disease, a genetic condition in which the red blood cells become rigid and sticky and change from being disc-shaped to being crescent-shaped (like a sickle). The recommendation followed a review by the CHMP of the results of the STAND study which showed that Adakveo did not reduce the number of painful crises leading to a healthcare visit when compared to placebo (a dummy treatment).
- Fluoroquinolone antibiotics: reminder of measures to reduce the risk of long-lasting, disabling and potentially irreversible side effects. These restrictions were introduced in 2019 following an EU-wide review of these very rare, but serious side effects. An EMA-funded study (EUPAS37856) has shown that although the use of fluoroquinolone antibiotics has decreased over time, these medicines are still prescribed outside of their recommended uses.
- Gavreto (pralsetinib), recommendation to evaluate patients for active and inactive (‘latent’) tuberculosis before starting treatment and to initiate standard antimycobacterial therapy in patients with active or latent tuberculosis before treatment with Gavreto. Also, avoid co-administration of pralsetinib with strong CYP3A4 inducers, or increase the dose of pralsetinib if co-administration cannot be avoided.
- Olumiant (baricitinib), recommendation to use a lower dose in patients at higher risk of blood clots, cardiovascular conditions, and cancer in line with the dosing recommendations for other JAK inhibitors used to treat several chronic inflammatory disorders.
- Omega-3-acid ethyl esters, recommendation to update the product information to add atrial fibrillation as a common side effect, to inform healthcare professionals and patients of the risk of atrial fibrillation, and to permanently discontinue treatment if atrial fibrillation develops.
- Pseudoephedrine-containing medicines, recommendation to not use pseudoephedrine in patients with severe or uncontrolled high blood pressure, or with severe acute or chronic kidney disease or failure, to minimise the risks of posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS). In addition, healthcare professionals should advise patients to stop using these medicines immediately and seek treatment if they develop symptoms of PRES or RCVS, such as severe headache with a sudden onset, feeling sick, vomiting, confusion, seizures, and visual disturbances.
- Topiramate-containing medicines, recommendation to not use topiramate for the treatment of epilepsy during pregnancy unless there is no other suitable treatment available, and to reassess at least annually the need for topiramate treatment in line with a new pregnancy prevention programme.
- Zolgensma (onasemnogene abeparvovec), updated recommendations on monitoring liver function, assessing suspected liver injury after infusion and further advice regarding tapering the corticosteroid treatment, following fatal cases of acute liver failure.
Ensuring integrity of clinical trial conduct and the manufacture and supply of medicines
Medicine development and manufacturing is global. It is important for regulators to ensure that EU standards are adhered to, no matter where clinical trials or manufacturing takes place.
In December, EMA recommended suspending the marketing authorisations of more than 350 generic medicines tested by Synapse Labs Pvt. Ltd, a contract research organisation (CRO) located in Pune, India. The recommendation followed a good clinical practice (GCP) inspection which showed that supporting data were lacking or insufficient to show bioequivalence. The list of the medicines concerned is available on EMA’s website.
Veterinary medicines
New medicines to benefit animal health in Europe
In 2023, EMA recommended 14 veterinary medicines for marketing authorisation. Of these, nine had a new active substance which had not previously been authorised in the EU – a threefold increase compared to 2022. Among the 14 medicines recommended for marketing authorisation, nine were vaccines, including six that had been developed by means of a biotechnological process (compared to one in 2022). This demonstrates the animal health industry’s continued strong interest in developing vaccines.
The new biotechnological vaccines include:
- Bovilis Cryptium, a new vaccine for the active immunisation of pregnant heifers and cows to raise antibodies in their colostrum against Gp40 of Cryptosporidium parvum. This is expected to provide passive immunisation of calves to reduce clinical signs (i.e. diarrhoea) caused by C. parvum.
- Innovax ILT-IBD, a new vaccine for the active immunisation of one-day-old chicks or 18-19-day-old embryonated chicken eggs to reduce mortality, clinical signs and lesions caused by avian infectious laryngotracheitis (ILT) virus and Marek’s disease virus and to prevent mortality and reduce clinical signs and lesions caused by infectious bursal disease (IBD) virus.
- Newflend ND H9, a new vaccine for the active immunisation of one-day-old chicks or 18-day-old chicken embryonated eggs to reduce clinical signs, lesions and virus shedding caused by Newcastle disease virus (NDV) and to reduce mortality, clinical signs, lesions, and virus shedding caused by H9 subtype of low pathogenic avian influenza virus (LPAIV-H9).
- Poulvac Procerta HVT-IBD, a new vaccine for the active immunisation of one-day-old chicks and 18-19 day-old embryonated chicken eggs to reduce mortality, clinical signs and lesions caused by Marek’s disease virus, and prevent mortality and clinical signs and reduce lesions caused by infectious bursal disease virus.
- Prevexxion RN+HVT, a new vaccine for the active immunisation of one-day-old chicks to prevent mortality and reduce clinical signs and lesions caused by Marek’s disease virus, including very virulent Marek’s disease virus.
- YURVAC RHD, a new vaccine for the active immunisation of rabbits from 30 days of age to reduce mortality of rabbit haemorrhagic disease (RHD) caused by classical RHD virus (RHDV) and variant strains (RHDV2), including highly virulent strains.
Optimising the safe and effective use of veterinary medicines
EMA and EU Member States continuously monitor the quality, safety and efficacy of the veterinary medicines on the market in the EU. The aim is to optimise the safe and effective use of a veterinary medicine, to achieve its full benefit and to protect animals and users from avoidable adverse effects. If the benefit-risk balance of a veterinary medicine changes, EMA can take regulatory measures that range from an amendment to the product information to the suspension or withdrawal of a medicine. The Agency can also recommend recalling batches of the medicine concerned.
Important new safety advice issued in 2023
The product information for six medicines was updated on the basis of new safety data. The revised information is expected to help animal owners and healthcare professionals to make informed decisions when using or prescribing a medicine. These included:
- Apoquel (oclacitinib maleate): Amendment to the product information on potential side effects following administration of Apoquel, to include convulsion.
- Cimalgex (cimicoxib): Amendment to the product information on potential side effects following the administration of Cimalgex, to include frequent urination and/or excessive thirst. A statement was also added to reflect that severe adverse events in the gastrointestinal tract and kidneys may be fatal.
- Galliprant (grapiprant): Amendment to the product information on potential side effects following the administration of Galliprant, to include pancreatic inflammation.
- Injectable veterinary medicines containing procaine benzylpenicillin: Recommendation not to use these veterinary medicines for the treatment of infections caused by certain pathogens. In addition, recommendation to update the product information to add potential side effects following the administration of these medicines in young piglets and new warnings to ensure their efficacious use. For some of these medicines, the dose and treatment duration were increased, and consequently the meat and offal withdrawal periods for all target species to ensure consumer safety.
- Neptra (florfenicol/terbinafine hydrochloride/mometasone furoate): Amendment to the product information for Neptra to include new special precautions for use in cats as it can be associated with neurological signs including ataxia (incoordination), Horner’s syndrome with protrusion of membrane nictitans (translucent third eyelid), miosis (constricted pupil), anisocoria (unequal pupil size), internal ear disorders (head tilt), anorexia and lethargy.
- Solensia (frunevetmab): Amendment to the product information on potential side effects following the administration of Solensia, to include anaphylaxis (severe allergic reaction) and skin disorders (e.g. skin scab, skin sore). In case of anaphylaxis, appropriate symptomatic treatment should be administered.
Protecting consumers of food of animal origin
If a medicine is intended to be used in a food-producing animal, it needs to be safe for people to eat the food that comes from this animal. EMA recommends maximum residue limits (MRLs) that reflect the level of residues of a veterinary medicine in food derived from a treated animal that can be considered safe for consumption. The MRL is established before a medicine can be authorised for food-producing animals in the EU.
If a marketing authorisation holder intends to apply for an extension of their marketing authorisation to another species, they must first obtain an extension to their MRL.
In 2023, positive opinions were adopted recommending the extension of MRLs for the following active substances:
- Sodium salicylate extension to poultry except turkey.
- Ketoprofen extension to poultry.
- Rafoxanide extrapolation to bovine, ovine and other ruminants’ milk.
More information and figures on veterinary medicines are available in chapter 2.
