CHMP Meeting Highlights December 2022
This month, medicinal products for the following indications have received a positive opinion:
- Haemophilia B (congenital factor IX deficiency)
- Hepatocellular carcinoma
- Non-small cell lung cancer
- Pompe disease (acid α-glucosidase deficiency)
New medicines recommended for approval:
Hemgenix (etranacogene dezaparvovec): received a positive opinion for a conditional marketing authorisation (CMA) for the treatment of severe and moderately severe Haemophilia B (congenital factor IX deficiency) in adult patients without a history of factor IX (FIX) inhibitors. For more information please consult the product for VidPrevtyn Beta on the EMA website.
Congenital haemophilia is an X-linked recessive disease caused by mutations in the genes coding for the coagulation factor VIII (haemophilia A) or IX (haemophilia B). It is characterised by the inability to form blood clots, which results in a higher risk of bruising, internal bleeding and bleeding inside the joints. The disease can be classified as mild, moderate or severe, depending on the endogenous plasma activity levels of clotting factors. Patients who are treated with anti-haemophilic factors to replace the deficient coagulation factor can develop anti-factor VIII or XI alloantibodies (inhibitors), which neutralise the activity of the administered replacement factors.
Hemgenix is an adeno-associated virus 5 (AAV5) vector that encodes FIX under the control of a liver-specific promoter. Hemgenix is designed for prolonged expression and is, therefore, delivered by a single intravenous dose. Hemgenix is an advanced therapy medicinal product (ATMP). For more information, please see the EMA news announcement on Hemgenix. For more information please consult the product for Hemgenix on the EMA website.
Imjudo (tremelimumab): received a positive opinion for the first line treatment of adults with advanced or unresectable hepatocellular carcinoma (HCC), in combination with durvalumab (see Imfinzi below).
HCC is the most common primary liver cancer (around 90% of cases). The incidence increases progressively with age and it is 2 to 3 times higher in men than in women. Some risk factors include chronic hepatitis B or C virus infection, high alcohol intake. Tremelimumab is a monoclonal antibody that targets the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). CTLA-4 is an immune checkpoint that acts by downregulating immune responses. By targeting and blocking CTLA-4, the checkpoint inhibitor tremelimumab activates the immune system, allowing T-lymphocytes to destroy cancer cells. For more information please consult the product for Imjudo on the EMA website.
Pombiliti (cipaglucosidase alfa): received a positive opinion for the treatment in combination with miglustat of adults with late-onset Pompe disease (acid α-glucosidase deficiency, glycogen storage disease type II).
Pompe disease is an autosomal recessive metabolic disease caused by a reduced or absent activity of the lysosomal alpha-glucosidase. As a consequence, glycogen accumulates in lysosomes, causing damage in the muscle (including heart) and nerve cells throughout the body. Pombiliti is a recombinant human alpha-glucosidase intended for enzyme replacement and it is conjugated with synthetic mannose 6-phosphate-rich glycans to enhance receptor targeting. Pombiliti has to be administered in combination with the enzyme stabiliser miglustat, which improves stability of cipaglucosidase in the bloodstream. For more information please consult the product for Pombiliti on the EMA website.
Tremelimumab AstraZeneca (tremelimumab): received a positive opinion for the first-line treatment of adults with metastatic non-small cell lung cancer (NSCLC) with no sensitising epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) positive mutations, in combination with durvalumab and platinum-based chemotherapy (see Imfinzi below).
NSCLC is a serious and often fatal disease that accounts for over 85% of all lung cancers. In NSCLC patients whose tumours lack driver mutations such as in the EGFR or ALK genes and can, therefore, not benefit from the respective targeted therapies, there is a high need for new and more efficacious therapies. Tremelimumab is a monoclonal antibody that targets CTLA-4 (see Imjudo above). For more information please consult the product for Tremelimumab on the EMA website.
Recommendations on extensions of therapeutic indication:
Adcirca (tadalafil): extension of indication to include the treatment of paediatric patients aged 2 years and above with pulmonary arterial hypertension classified as WHO functional class II and III. Adcirca was already authorised in adults. For more information please consult the product for Adcirca on the EMA website.
Dupixent (dupilumab): extension of indication to the treatment of eosinophilic esophagitis in adults and adolescents 12 years and older, weighing at least 40 kg, who are inadequately controlled by, are intolerant to, or who are not candidates for conventional medicinal therapy. Dupixent was already authorised for the treatment of prurigo nodularis, atopic dermatitis, asthma and chronic rhinosinusitis with nasal polyposis. For more information please consult the product for Lyumjev on the EMA website.
Edistride (dapagliflozin) and Forxiga (dapagliflozin): extension of indication to the treatment of adults with symptomatic chronic heart failure. Edistride and Forxiga were previously only authorised in adult patients with reduced ejection fraction. Furthermore, they were also already authorised for the treatment of type 2 diabetes mellitus and chronic kidney disease. For more information please consult the product for Edistride on the EMA website.
Enhertu (trastuzumab deruxtecan): extension of indication to include the treatment as monotherapy of adult patients with unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-low breast cancer who have received prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy. Enhertu was already authorised for gastric cancer and HER2-positive breast cancer (only in patients who have received one or more prior anti-HER2-based regimens). For more information please consult the product for Enhertu on the EMA website.
Fintepla (fenfluramine): extension of indication to include the treatment of seizures associated with Lennox-Gastaut syndrome as an add-on therapy to other anti-epileptic medicines for patients 2 years of age and older. Fintepla was already authorised for the treatment of seizures associated with Dravet syndrome. For more information please consult the product for Fintepla on the EMA website.
Hemlibra (emicizumab): extension of indication to the routine prophylaxis of bleeding episodes in patients with haemophilia A without factor VIII inhibitors who have moderate disease (factor VIII (FVIII) ≥ 1% and ≤ 5%) with severe bleeding phenotype. Hemlibra was already authorised in patients with factor VIII inhibitors and without factor VIII inhibitors who have severe disease (FVIII < 1%). For more information please consult the product for Hemlibra on the EMA website.
Imfinzi (durvalumab): has received this month a positive opinion for two new indications:
- the first-line treatment of adults with metastatic non-small cell lung cancer with no sensitising epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) positive mutations, in combination with tremelimumab and platinum-based chemotherapy (see Tremelimumab AstraZeneca above).
- the first line treatment of adults with advanced or unresectable hepatocellular carcinoma, in combination with tremelimumab (see Imjudo above).
Imfinzi was already authorised for the treatment of small cell lung cancer, biliary tract cancer and non-small cell lung cancer with programmed cell death ligand-1 (PD-L1) expression ≥ 1%. For more information please consult the product for Imfinzi on the EMA website.
Kerendia (finerenone): extension of indication to the treatment of chronic kidney disease (with albuminuria) associated with type 2 diabetes in adults. Kerendia was previously only authorised in patients with stage 3 and 4 chronic kidney disease (with albuminuria). For more information please consult the product for Kerendia on the EMA website.
Triumeq (dolutegravir / abacavir / lamivudine): extension of indication for the film-coated tablets to the treatment of Human Immunodeficiency Virus (HIV) infected-children weighing at least 25 kg. Triumeq film-coated tablets is also authorised in adults.
Furthermore, Triumeq dispersible tablets received a positive opinion for the treatment of HIV-infected children weighing at least 14 kg to less than 25 kg. For more information please consult the product for Triumeq 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:
Beyfortus (nirsevimab): is indicated for the prevention of Respiratory Syncytial Virus (RSV) lower respiratory tract disease in neonates and infants during their first RSV season. EPAR Beyfortus.
Enjaymo (sutimlimab): is indicated for the treatment of haemolytic anaemia in adult patients with cold agglutinin disease. EPAR Enjaymo.
Livmarli (maralixibat chloride): is indicated for the treatment of cholestatic pruritus in patients with Alagille syndrome 2 months of age and older. EPAR Livmarli.
Livtencity (maribavir): is indicated for the treatment of cytomegalovirus infection and/or disease that are refractory (with or without resistance) to one or more prior therapies, including ganciclovir, valganciclovir, cidofovir or foscarnet in adult patients who have undergone a haematopoietic stem cell transplant or solid organ transplant. EPAR Livtencity.
Mounjaro (tirzepatide): is indicated for the treatment of adults with insufficiently controlled type 2 diabetes mellitus as an adjunct to diet and exercise. EPAR Mounjaro.
- as monotherapy when metformin is considered inappropriate due to intolerance or contraindications;
- in addition to other medicinal products for the treatment of diabetes.
Pyrukynd (mitapivat): is indicated for the treatment of pyruvate kinase deficiency in adult patients. EPAR Pyrukynd.
Qdenga (dengue tetravalent vaccine [live, attenuated]): is indicated for the prevention of dengue disease in individuals from 4 years of age. EPAR Qdenga.
VidPrevtyn Beta (COVID-19 Vaccine [recombinant, adjuvanted]): is indicated as a booster for active immunisation to prevent COVID-19 in adults who have previously received an mRNA or adenoviral vector COVID-19 vaccine. EPAR VidPrevtyn Beta.
Recently started procedures:
- Catumaxomab - Indicated for the treatment of malignant ascites.
- Cedazuridine / decitabine - Orphan - Treatment of myeloid leukaemia.
- Elacestrant - Treatment of men and postmenopausal women with breast cancer.
- GBP510 - Prevention of COVID-19 caused by SARS-CoV-2 in individuals 18 years of age and older.
- Guizartinib - Orphan - Treatment of adult patients with diagnosed acute myeloid leukaemia.
- Leriglitazone - Treatment of cerebral progression and myelopathy in male patients with adrenoleukodystrophy.
- Masitinib - Orphan - In combination with riluzole for the treatment of adult patients with amyotrophic lateral sclerosis.
- Pegzilarginase - Treatment of hyperargininemia.
- Rezafungin - Orphan - Treatment of invasive candidiasis.
- Ritlecitinib - Indicated for the treatment of severe alopecia areata in adults and adolescents 12 years of age and older.
- Sparsentan - Orphan - Treatment of primary immunoglobulin A nephropathy.
Other topics of interest
Referral procedure under Article 29(4) for Gelisia (timolol maleate) and Rambis (ramipril/bisoprolol fumarate):
The CHMP completed a review of Gelisia following a disagreement among EU Member States regarding two medicine authorisations. The committee concluded that the benefits of Gelisia outweigh its risks and the marketing authorisation should be granted in the Netherlands and in the other EU Member States where the company has applied for a marketing authorisation (France, Germany, Italy, Romania and Spain). Gelisia is an eye gel that is used to reduce pressure inside the eye in adults who have ocular hypertension. For more information about this referral, please visit the EMA announcement on the Gelisia referral.
The committee concluded by majority that the benefits of Rambis outweigh its risks, with the provided pharmacological reasoning being a sufficient justification of the combination of ramipril and bisoprolol, and the marketing authorisation should be granted in Poland and in the other EU Member States where the company has applied for a marketing authorisation (Czechia and Slovakia). Rambis is a medicine for patients with certain long-term heart conditions and high blood pressure. For more information please visit the EMA announcement on the Rambis referral.
Update on the following authorised medicines for the prevention of COVID-19:
The CHMP has recommended extending the indication of COVID-19 vaccine Spikevax (original) and Spikevax bivalent Original/Omicron BA.1 as a booster dose in children aged 6 to 11 years.
The COVID-19 vaccine Jcovden has been recommended for a switch from CMA to standard authorisation following the submission of data that fulfils the outstanding specific obligations.