CHMP Meeting Highlights July 2024 New
This month, medicinal products for the following indications have received a positive opinion:
- Chronic hand eczema
- Primary biliary cholangitis
- Cholestatic pruritus in Alagille syndrome
- Nasopharyngeal carcinoma + Oesophageal squamous cell carcinoma
- Moderate to severe dry eye disease (keratoconjuctivitis sicca)
- Gastric or gastro-oesophageal junction adenocarcinoma
- Pulmonary arterial hypertension
New medicines recommended for approval:
Anzupgo (delgocitinib): has received a positive opinion for the treatment of moderate to severe chronic hand eczema (CHE) in adults for whom topical corticosteroids are inadequate or inappropriate.
Chronic hand eczema is a common, inflammatory disorder involving the skin of the hands. Symptoms include redness, blistering, cracking and itching. It can have a severe impact on quality of life.
Delgocitinib is a JAK (Janus kinase) inhibitor which inhibits four different enzymes involved in proinflammatory signaling pathways. This inhibition shall lead to a downregulation of the immune and inflammatory responses which are considered as causative for the development of CHE. For more information please consult the product for Anzupgo on the EMA website.
Iqirvo (elafibranor): has received a positive opinion for a conditional marketing authorisation for the treatment of primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) in adults with an inadequate response to UDCA, or as monotherapy in patients unable to tolerate UDCA.
Primary biliary cholangitis (formerly known as primary biliary cirrhosis) is an autoimmune disease in which the bile ducts are inflamed and slowly destroyed, causing bile and other toxins accumulate in the liver. This accumulation can ultimately lead to liver fibrosis and cirrhosis.
Elafibranor binds to the α and δ subtypes of the peroxisome proliferator-activated receptor (PPAR) which are key regulators of bile acid homeostasis, inflammation and fibrosis, leading to a reduction in bile acid accumulation and inflammation. For more information please consult the product for Iqirvo on the EMA website.
Kayfanda (odevixibat): has received a positive opinion for a marketing authorisation under exceptional circumstances for the treatment of cholestatic pruritus in Alagille syndrome (ALGS) in patients aged 6 months or older.
Alagille syndrome is a rare genetic disorder caused by mutations in the JAG1 gene or, much less commonly, in the NOTCH2 gene, both encoding proteins involved in the Notch-signalling cascade. Although it presents with variable penetrance and clinical manifestations, the liver and heart are usually affected. Hepatic manifestations often include cholestatic pruritus, an itchy sensation caused by elevated serum bile acids (sBA) and the most burdensome symptom.
Odevixibat is a reversible and selective inhibitor of the ileal bile acid transporter (IBAT) that acts locally in a certain part of the small intestine. It reduces the reuptake of bile acids and increases the clearance of bile acids through the large intestine. For more information please consult the product for Kayfanda on the EMA website.
Loqtorzi (toripalimab): has received a positive opinion for the following two indications:
- Loqtorzi, in combination with cisplatin and gemcitabine, is indicated for the first-line treatment of adult patients with recurrent, not amenable to surgery or radiotherapy, or metastatic nasopharyngeal carcinoma.
- Loqtorzi, in combination with cisplatin and paclitaxel, is indicated for the first-line treatment of adult patients with unresectable advanced, recurrent, or metastatic oesophageal squamous cell carcinoma.
Toripalimab is a monoclonal antibody targeting the PD-1 receptor (programmed death protein 1), which is expressed on T cells. Many cancer cells in various tissues express PD-L1 (programmed cell death ligand 1), the ligand for PD-1. This overexpression represents an immune evasion mechanism, since activation of PD-1 down-regulates the immune system, blocks the interaction between PD-1 and PD-L1 and enhances the T cell responses against the cancer cells.
Both nasopharyngeal cancer and oesophageal cancer are rare diseases in Europe, but belong to the most common cancers worldwide. They are highly fatal diseases and a major cause of cancer mortality. For more information please consult the product for Loqtorzi on the EMA website.
Vevizye (ciclosporin): has received a positive opinion for the treatment of moderate to severe dry eye disease (keratoconjuctivitis sicca) in adult patients, which has not improved despite treatment with tear substitutes.
Dry eye disease is caused by an impaired ability to produce a sufficient tear layer in the eye. Symptoms include dryness in the eye, pain, redness, tearing, and blurred vision. Patients with dry eye disease have an increased risk of long-term impairment of the eyes up to loss of vision.
Ciclosporin is an immunosuppressant which is well-known since decades, e.g. for its use in transplanted patients. It inhibits calcineurin which is involved in inflammatory pathways. The inhibition of inflammation leads to reduced disease symptoms. For more information please consult the product for Vevizye on the EMA website.
Vyloy (zolbetuximab): has received a positive opinion, in combination with fluoropyrimidine- and platinum-containing chemotherapy, for the first-line treatment of adult patients with locally advanced unresectable or metastatic HER2-negative gastric or gastro-oesophageal junction (GEJ) adenocarcinoma whose tumours are Claudin (CLDN) 18.2 positive.
Gastric cancer, and also cancer at the link between the stomach and the oesophagus (gastro-oesophageal junction/GEJ), is a common cancer type and still a leading cause of death. It is usually detected in an advanced or metastatic stage, when first symptoms like weight loss and abdominal pain occur. A regular screening which allows early diagnosis (and thus, earlier treatment) is performed only in few non-European countries with high incidence.
Zolbetuximab is a monoclonal antibody which targets Claudin 18.2, a tight junction protein which is exclusively expressed in gastric mucosa cells. Upon malignant transformation, this protein typically keeps being expressed and is only rarely downregulated. It is therefore a promising target in the treatment of gastric and GEJ cancer. For more information please consult the product for Vyloy on the EMA website.
Yuvanci (macitentan / tadalafil): has received a positive opinion, as substitution therapy, for the long-term treatment of pulmonary arterial hypertension (PAH) in adult patients of WHO Functional Class (FC) II to III, who are already treated with the combination of macitentan and tadalafil given concurrently as separate tablets.
Pulmonary arterial hypertension (PAH) is high blood pressure in the blood vessels which lead from the heart to the lung. PAH is a rare condition and is associated with difficulty to breathe, chest pain and dizziness. As the heart needs to work harder to pump blood into the lung, it may eventually be affected. PAH can be a life-threatening disease.
Yuvanci represents a fixed dose combination of two active substances, macitentan and sildenafil. Both substances have an antihypertensive effect. Macitentan reduces vasoconstriction by binding to the endothelin receptor on smooth muscle cells, while taldalafil acts on PDE5 (phosphodiesterase 5) which also has a vasodilatating effect specifically in the pulmonary smooth muscles. Thus, the effect of the combination treatment is the reduction in pulmonary blood pressure. For more information please consult the product for Yuvanci on the EMA website.
Recommendations on extensions of therapeutic indication:
Arexvy (respiratory syncytial virus (RSV) vaccine (recombinant, adjuvanted)): extension of indication to include the following indication:
- Arexvy is indicated for active immunisation for the prevention of lower respiratory tract disease (LRTD) caused by respiratory syncytial virus in adults 50 through 59 years of age who are at increased risk for RSV disease.
Arexvy is already authorised in patients 60 years of age and older. For more information please consult the product for Arexvy on the EMA website.
Braftovi (encorafenib): extension of indication to include the following indication:
- Encorafenib in combination with binimetinib is indicated for the treatment of adult patients with advanced non-small cell lung cancer with a BRAF V600E mutation.
Braftovi is already authorised for melanoma and colorectal cancer. For more information please consult the product for Braftovi on the EMA website.
Edurant (rilpivirine): extension of indication to include the following indication and a new, age-appropriate pharmaceutical form, 2.5 mg dispersible tablets:
- Edurant, in combination with other antiretroviral medicinal products, is indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in paediatric patients 2 to less than 18 years of age and weighing at least 14 kg to less than 25 kg without known mutations associated with resistance to the non-nucleoside reverse transcriptase inhibitor (NNRTI) class, and with a viral load ≤ 100,000 HIV-1 RNA copies/ml.
The already existing therapeutic indication refers to a different pharmaceutical form, 25 mg film-coated tablets. This indication was also adapted, namely to include a weight restriction instead of an age restriction (formerly: 12 years of age and older; now: weighing at least 25 kg) and to delete the requirement to be treatment naïve. The full new indication for the 25 mg film-coated tablet formulation is:
- Edurant, in combination with other antiretroviral medicinal products, is indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults and paediatric patients weighing at least 25 kg without known mutations associated with resistance to the non-nucleoside reverse transcriptase inhibitor (NNRTI) class, and with a viral load ≤ 100,000 HIV-1 RNA copies/ml.
For more information please consult the product for Edurant on the EMA website.
Keytruda (pembrolizumab): extension of indication to include the following indication:
- Keytruda, in combination with enfortumab vedotin, is indicated for the first-line treatment of unresectable or metastatic urothelial carcinoma in adults.
Keytruda is already authorised for a variety of solid tumours, including also different treatment settings in urothelial carcinoma. For more information please consult the product for Keytruda on the EMA website.
Mektovi (binimetinib): extension of indication to include the following indication:
- Binimetinib in combination with encorafenib is indicated for the treatment of adult patients with advanced non-small cell lung cancer with a BRAF V600E mutation.
Mektovi is already authorised for the treatment of melanoma. For more information please consult the product for Mektovi on the EMA website.
Opsumit (macitentan): extension of indication to include the following indication and a new, age-appropriate pharmaceutical form, 2.5 mg dispersible tablets:
- Opsumit, as monotherapy or in combination, is indicated for the long-term treatment of pulmonary arterial hypertension (PAH) in paediatric patients aged 2 years to less than 18 years with WHO Functional Class (FC) II to III.
The existing therapeutic indication, for adult patients, refers to a different pharmaceutical form, 10 mg film-coated tablets. This indication was also adapted, to include paediatric patients with a bodyweight ≥ 40 kg. For more information please consult the product for Opsumit on the EMA website.
Padcev (enfortumab vedotin): extension of indication to include the following indication:
- Padcev, in combination with pembrolizumab, is indicated for the first-line treatment of adult patients with unresectable or metastatic urothelial cancer who are eligible for platinum-containing chemotherapy.
Padcev is already authorised for the treatment of urothelial carcinoma, however as monotherapy and for a different treatment setting. For more information please consult the product for Padcev on the EMA website.
Rybrevant (amivantamab): extension of indication to include the following indication:
- Rybrevant is indicated in combination with carboplatin and pemetrexed for the treatment of adult patients with advanced non-small cell lung cancer (NSCLC) with EGFR Exon 19 deletions or Exon 21 L858R substitution mutations after failure of prior therapy including an EGFR tyrosine kinase inhibitor (TKI).
Rybrevant is already authorised for the treatment of NSCLC in different treatment settings. For more information please consult the product for Rybrevant on the EMA website.
Slenyto (melatonin): extension of indication to include the following indication:
- Slenyto is indicated for the treatment of insomnia in children and adolescents aged 2-18 with neurogenetic disorders with aberrant diurnal melatonin secretion and /or nocturnal awakenings, where sleep hygiene measures have been insufficient.
Slenyto is already authorised for the treatment of insomnia in children and adolescents aged 2-18 with Autism Spectrum Disorder (ASD) and / or Smith-Magenis syndrome. For more information please consult the product for Slenyto on the EMA website.
Spevigo (spesolimab): extension of indication to include the following indication:
- Spevigo is indicated for the prevention of generalised pustular psoriasis (GPP) flares in adults and adolescents from 12 years of age.
Spevigo is already authorised for the treatment of GPP flares in adults. This indication was extended this month to include adolescents from 12 years of age. For more information please consult the product for Spevigo on the EMA website.
Tecentriq (atezolizumab): extension of indication to include the following indication:
- Tecentriq as monotherapy is indicated for the first-line treatment of adult patients with advanced NSCLC who are ineligible for platinum-based therapy (see section 5.1 for selection criteria).
Tecentriq is already authorised for different treatment settings in NSCLC, as well as small cell lung cancer (SCLC), breast cancer, urothelial carcinoma, and hepatocellular carcinoma. For more information please consult the product for Tecentriq on the EMA website.
Newly published EPARs:
The EPAR (European public assessment report) is the main document where the EMA publishes detailed information on the medicines assessed by the CHMP. Below is a list of the EPARs for recently approved products that have been made available on the EMA homepage:
Altuvoct (efanesoctocog alfa): is indicated for the treatment and prophylaxis of bleeding in patients with haemophilia A (congenital factor VIII deficiency). It can be used for all age groups. EPAR Altuvoct.
Fluenz (influenza vaccine (live attenuated, nasal)): is indicated for the prophylaxis of influenza in children and adolescents from 24 months to less than 18 years of age. EPAR Fluenz.
Fruzaqla (fruquintinib): as monotherapy is indicated for the treatment of adult patients with metastatic colorectal cancer (mCRC) who have been previously treated with available standard therapies, including fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapies, anti-VEGF agents, and anti-EGFR agents, and who have progressed on or are intolerant to treatment with either trifluridine-tipiracil or regorafenib. EPAR Fruzaqla.
Ixchiq (Chikungunya vaccine (live)): is indicated for active immunisation for the prevention of disease caused by chikungunya virus (CHIKV) in individuals 18 years and older. EPAR Ixchiq.
Jeraygo (aprocitentan): is indicated for the treatment of resistant hypertension in adult patients in combination with at least three antihypertensive medicinal products. EPAR Jeraygo.
Obgemsa (vibegron): in symptomatic treatment of adult patients with overactive bladder (OAB) syndrome. EPAR Obgemsa.
Truqap (capivasertib): is indicated in combination with fulvestrant for the treatment of adult patients with oestrogen receptor (ER)-positive, HER2-negative locally advanced or metastatic breast cancer with one or more PIK3CA/AKT1/PTEN-alterations following recurrence or progression on or after an endocrine-based regimen (see section 5.1).
In pre- or perimenopausal women, Truqap plus fulvestrant should be combined with a luteinising hormone releasing hormone (LHRH) agonist.
For men, administration of LHRH agonist according to current clinical practice standards should be considered. EPAR Truqap.
