CHMP Meeting Highlights February 2024
This month, medicinal products for the following indications have received a positive opinion:
- Active immunisation against H5N1 subtype of Influenza A virus
- Primary immunoglobulin A nephropathy (IgAN)
- Active immunisation against influenza in an officially declared pandemic
- Amyotrophic lateral sclerosis (ALS)
- Non-small cell lung cancer (NSCLC)
- Paroxysmal nocturnal haemoglobinuria (PNH)
- Merkel cell carcinoma (MCC)
New medicines recommended for approval:
New medicines recommended for approval:
Two products for the active immunisation against H5N1 subtype of influenza A virus received a positive opinion this month:
Celldemic (zoonotic influenza vaccine (H5N1):(surface antigen, inactivated, adjuvanted, prepared in cell cultures)) received a positive opinion for the active immunisation against H5N1 subtype of Influenza A virus in adults and infants from 6 months of age and above. For more information please consult the product for Celldemic on the EMA website.
Incellipan (pandemic influenza vaccine (H5N1): (surface antigen, inactivated, adjuvanted, prepared in cell cultures) received a positive opinion for the active immunisation against influenza in an officially declared pandemic.
Both products are identical, but are intended to target different applications (zoonotic vs. pandemic vaccine).
Influenza subtype H5N1 is a zoonotic virus, which primarily occurs in birds (“bird flu”) and can be transmitted to humans. Pandemic influenza outbreaks can occur when a new highly infectious virus strain enters a population with low immunity from previous exposure. Infection with influenza virus usually occurs by droplet spread from infected people to uninfected people through inhalation. The viral infection can cause fever, cough and breathing problems up to pneumonia in humans. Although human transmission of H5N1 is rare, the mortality rate from H5N1 infection is high.
Filspari (sparsentan): received a positive opinion, recommending the granting of a conditional marketing authorisation, for the treatment of adults with primary immunoglobulin A nephropathy (IgAN) with a urine protein excretion >1.0 g/day (or urine protein-to-creatinine ratio ≥0.75 g/g).
IgAN, also known as Berger’s disease, is a progressive autoimmune glomerulonephritis characterised by galactose-deficient IgA1 (GdIgA1) deposits within the glomeruli of the kidney. This accumulation triggers inflammatory events, ultimately causing irreversible scarring of the glomeruli (glomerulosclerosis) and loss of filtration capacity. The primary form of the disease is characterised by the lack of relevant associated co-morbidities. Although the aetiology is unknown, it has been shown that the mucosal immune system (particularly of the gastrointestinal tract) is involved in the development of the disease.
Sparsentan is a dual-acting, selective antagonist for endothelin type A receptor (ETAR) and angiotensin II receptor type 1 (AT1R). Inhibition of these receptors leads to suppression of proteinuria and glomerulosclerosis during the development and progression of kidney disease. For more information please consult the product for Filspari on the EMA website.
Qalsody (tofersen): received a positive opinion, recommending the granting of a marketing authorisation under exceptional circumstances, for the treatment of adults with amyotrophic lateral sclerosis (ALS), associated with a mutation in the superoxide dismutase 1 (SOD1) gene.
ALS is a severe neurological disease that leads to paralysis and spasticity. The mean survival time with ALS is two to five years. There is only one authorised treatment for ALS, and the unmet medical need remains high. In a small proportion of ALS patients, the disease is caused by a mutation in the SOD1 gene, which results in the production of defective SOD1 proteins and causes aberrations in neurons.
Qalsody is an antisense oligonucleotide that binds to the mRNA of the SOD1 gene to reduce SOD1 protein production. By reducing the amount of defective SOD1 protein, this medicine is expected to improve the symptoms of ALS.
The EMA has published a press release on Qalsody. For more information please consult the product for Qalsody on the EMA website.
Tizveni (tislelizumab): has received a positive opinion for the following indications:
- Tizveni in combination with pemetrexed and platinum-containing chemotherapy is indicated for the first-line treatment of adult patients with non-squamous non-small cell lung cancer whose tumours have PD-L1 expression on ≥50% of tumour cells with no EGFR or ALK positive mutations and who have:
- locally advanced NSCLC and are not candidates for surgical resection or platinum-based chemoradiation, or
- metastatic NSCLC
- Tizveni in combination with carboplatin and either paclitaxel or nab-paclitaxel is indicated for the first-line treatment of adult patients with squamous non-small cell lung cancer who have:
- locally advanced NSCLC and are not candidates for surgical resection or platinum-based chemoradiation, or
- metastatic NSCLC
- Tizveni as monotherapy is indicated for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer after prior platinum-based therapy. Patients with EGFR mutant or ALK positive NSCLC should also have received targeted therapies before receiving tislelizumab.
Non-small cell lung cancer (NSCLC) is a serious and often fatal disease that accounts for 80 to 85% of all lung cancers. A significant number of patients present with driver mutations in oncogenes, some of which can be aimed at by targeted therapies. Patients without known driver mutations need broader-acting therapies.
Tislelizumab is a checkpoint inhibitor, targeting PD-1 (programmed cell death protein 1) on immune cells. Many cancer cells express a PD-1 ligand. Since activation of PD-1 down-regulates the immune system, blocking of the interaction between PD-1 and PD-L1 enhances the T cell responses against the cancer cells. Furthermore, tislelizumab was engineered to reduce Fc-mediated effector protein bindings, thereby reducing the antibody- and complement-dependent cytotoxicity. For more information please consult the product for Tizveni on the EMA website.
Voydeya (danicopan): received a positive opinion as an add-on to ravulizumab or eculizumab for the treatment of adult patients with paroxysmal nocturnal haemoglobinuria (PNH) who have residual haemolytic anaemia.
PNH is a life-threatening blood disorder characterised by the destruction of red blood cells by the complement system, a component of the immune system. This occurs most commonly as a result of a somatic mutation that alters the exterior surface proteins of red blood cells, rendering these susceptible to be attacked by the complement.
Danicopan is an orally available inhibitor of the alternative pathway of the complement system. When combined with a complement C5 inhibitor, haemolysis and increased haemoglobin levels can be prevented. The development of Voydeya was supported through EMA's PRIority MEdicines (PRIME) scheme, which provides early and enhanced scientific and regulatory support.
The EMA has published a press release on Voydeya. For more information please consult the product for Voydeya on the EMA website.
Zynyz (retifanlimab): has received a positive opinion for the first-line treatment, as monotherapy, of adult patients with metastatic or recurrent locally advanced Merkel cell carcinoma (MCC) not amenable to curative surgery or radiation therapy.
Merkel cell carcinoma is a rare, aggressive malignancy of the skin with a poor outcome when advanced. The carcinoma originates predominantly on light-exposed parts of the skin. The disease primarily affects old and/or immunosuppressed patients.
Like Tizveni/tislelizumab (see information above), retifanlimab is also a checkpoint inhibitor targeting PD-1. For more information please consult the product for Zynyz on the EMA website.
Recommendations on extensions of therapeutic indication:
Carvykti (ciltacabtagene autoleucel): extension of indication to include treatment of adult patients with relapsed and refractory multiple myeloma, who have received at least one prior therapy, including an immunomodulatory agent and a proteasome inhibitor and have demonstrated disease progression on the last therapy, and are refractory to lenalidomide.
Carvykti is already authorised for a later line of treatment of multiple myeloma. For more information please consult the product for Carvykti on the EMA website.
Cibinqo (abrocitinib): extension of indication to include the treatment of moderate-to-severe atopic dermatitis in adolescents 12 years and older who are candidates for systemic therapy.
Cibinqo is already authorised for adult patients with moderate-to-severe atopic dermatitis. For more information please consult the product for Cibinqo on the EMA website.
Kalydeco (ivacaftor): extension of indication to include the treatment, as monotherapy, of infants aged at least 1 month, toddlers and children weighing 3 kg to less than 25 kg with cystic fibrosis (CF) who have an R117H CFTR mutation or one of the following gating (class III) mutations in the CFTR gene: G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N or S549R.
Kalydeco is already authorised for the treatment of patients aged 4 months and above, weighing at least 3 kg, carrying one of the above-listed mutations. In addition, it is authorised in a combination regimen with ivacaftor/tezacaftor/elexacaftor for the treatment of paediatric patients aged 2 to less than 6 years who have at least one F508del mutation in the CFTR gene. For more information please consult the product for Kalydeco on the EMA website.
Keytruda (pembrolizumab): extension of indication to include Keytruda, in combination with platinum-containing chemotherapy as neoadjuvant treatment, and then continued as monotherapy as adjuvant treatment, for the treatment of resectable non‑small cell lung carcinoma at high risk of recurrence in adults.
Keytruda is already authorised for the treatment of various types of solid cancer, including NSCLC in different therapeutic settings and lines of therapy. For more information please consult the product for Keytruda on the EMA website.
Reblozyl (luspatercept): extension of indication to include the treatment of all patients with transfusion-dependent anaemia due to very low, low and intermediate-risk myelodysplastic syndromes (MDS), regardless of age, prior therapies and eligibility for erythropoietin-based therapy.
Reblozyl is already authorised for adults only, with some restrictions regarding symptoms and prior therapies. For more information please consult the product for Reblozyl on the EMA website.
Xromi (hydroxycarbamide): extension of indication to include the prevention of vaso-occlusive complications of Sickle Cell Disease (SCD) in patients over 9 months of age.
Xromi is already authorised for the treatment of SCD in older children from 2 years of age. For more information please consult the product for Xromi 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:
Elucirem and Vueway (identical duplicate products, containing gadopiclenol): are for diagnostic use only. They are indicated in adults and children aged 2 years and older for contrast-enhanced magnetic resonance imaging (MRI) to improve detection and, visualization of pathologies with disruption of the blood-brain-barrier (BBB) and/or abnormal vascularity of:
- the brain, spine, and associated tissues of the central nervous system (CNS);
- liver, kidney, pancreas, breast, lung, prostate, and musculoskeletal system.
They should be used only when diagnostic information is essential and not available with unenhanced MRI. EPAR Elucirem/EPAR Vueway.
Omjjara (momelotinib): is indicated for the treatment of disease-related splenomegaly or symptoms in adult patients with moderate to severe anaemia who have primary myelofibrosis, post polycythaemia vera myelofibrosis or post essential thrombocythaemia myelofibrosis and who are Janus Kinase (JAK) inhibitor naïve or have been treated with ruxolitinib. EPAR Omjjara.
Velsipity (etrasimod): is indicated for the treatment of patients 16 years of age and older with moderately to severely active ulcerative colitis (UC) who have had an inadequate response, lost response, or were intolerant to either conventional therapy, or a biological agent. EPAR Velsipity.
Previous CHMP Meeting Highlights can be accessed at: https://www.basg.gv.at/en/healthcare-professionals/chmp-highlights
