CHMP Meeting Highlights October 2023

CHMP Monthly News | 30/10/2023

This month, medicinal products for the following indications have received a positive opinion:

Duchenne muscular dystrophy
Multiple myeloma
Hyperargininemia
Invasive candidiasis
Vasomotor symptoms (VMS) associated with menopause
Detection and visualization of pathologies with disruption of the blood-brain-barrier (BBB) and/or abnormal vascularity (for diagnostic use)

New medicines recommended for approval:

Agamree (vamorolone): is indicated for the treatment of Duchenne muscular dystrophy (DMD) in patients aged 4 years and older.

DMD is a rare, severe muscle wasting disease, which affects boys from birth and is invariably fatal due to the lack of dystrophin, a structural and regulatory protein at the membranes of muscle fibres.

It is caused by errors in the gene encoding dystrophin, an essential cohesive protein which connects muscle fibers with the surrounding extracellular matrix. The dystrophin gene is located on the X-chromosome, therefore DMD is inherited in an X-chromosomal recessive manner. Vamorolone is a corticosteroid that was designed to separate sub-activities of traditional glucocorticoids (such as prednisone). One important characteristic is the stabilisation of plasma membranes with protection against membrane injury. For more information please consult the product for Agamree on the EMA website.

Elrexfio (elranatamab): received a positive opinion for a conditional marketing authorisation (CMA) for the treatment, as monotherapy, of adult patients with relapsed and refractory multiple myeloma (MM), who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody and have demonstrated disease progression on the last therapy.

MM is a type of blood cancer characterised by the malignant proliferation of plasma cells that consistently express the B-cell maturation antigen (BCMA). BCMA is not expressed in normal non-haematopoietic cells. Elrexfio is a bispecific antibody that targets CD3, present on the surface of T-cells, and BCMA. Elrexfio binds CD3, thereby eliciting recruitment of effector T-cells. Upon concurrent binding with BCMA, T-cell activation occurs, resulting in T-cell-mediated B-cell lysis. For more information please consult the product for Elrexfio on the EMA website.

Elucirem/Vueway (gadopiclenol) is for diagnostic use only. It is 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.

It should be used only when diagnostic information is essential and not available with unenhanced MRI.

Gadopiclenol is a macrocyclic contrast agent based on gadolinium. Compared with standard gadolinium-based contrast agents, gadopiclenol shows differing spectroscopic characteristics and can thus be used in lower doses. For more information please consult the product for Elucirem on the EMA website.

Loargys (pegzilarginase): received a positive opinion for a marketing authorisation under exceptional circumstances for the treatment of arginase 1 deficiency (ARG1-D), also known as hyperargininemia, in adults, adolescents and children aged 2 years and older.

Hyperargininaemia is a rare, debilitating, progressive, inherited, metabolic disease. It is characterised by deficiency of the arginase 1 enzyme and associated with the persistent elevation of plasma arginine leading to progressive neurodegenerative symptoms. Patients present with the development of progressive spasticity with greater severity in the lower limbs. They may also develop seizures and gradually lose intellectual attainments. Treatment with Loargys aims at substitution of the deficient ARG1 enzyme activity. For more information please consult the product for Loargys on the EMA website.

Rezzayo (rezafungin): is indicated for the treatment of invasive candidiasis in adults.

Invasive candidiasis is a serious and life-threatening infection caused by Candida species, associated with high mortality rates. It can cause invasive disease characterised by both widely disseminated and/or bloodstream infections. Rezafungin selectively inhibits 1,3-β-D-glucan synthase, an enzyme present in fungal, but not mammalian, cells. This results in inhibition of the formation of 1,3-β-D-glucan, an essential component of the fungal cell wall. For more information please consult the product for Rezzayo on the EMA website.

Veoza (fezolinetant): is indicated for the treatment of moderate to severe vasomotor symptoms (VMS) associated with menopause.

VMS, also referred to as hot flashes, involve sudden episodes of heat in the upper body, particularly in the head, neck, chest and upper back. Fezolinetant inhibits the neurokinin 3 receptor which is expressed in the central nervous system. This inhibition results in a blockade of a signaling pathway involved in the thermoregulatory center of the brain, and ultimately leads to reduced VMS. For more information please consult the product for Veoza on the EMA website.

Recommendations on extensions of therapeutic indication:

Brukinsa (zanubrutinib): extension of indication to, in combination with obinutuzumab, the treatment of adult patients with refractory or relapsed follicular lymphoma (FL) who have received at least two prior systemic therapies.

Brukinsa was already authorised for the treatment of Waldenström’s macroglobulinaemia, marginal zone lymphoma and chronic lymphocytic leukaemia. For more information please consult the product for Brukinsa on the EMA website.

Imfinzi (durvalumab): extension of indication to include, as monotherapy, the first line treatment of adults with advanced or unresectable hepatocellular carcinoma (HCC).

Imfinzi was already authorised, as a combination therapy with chemotherapeutic agents and/or tremelimumab, for the treatment of HCC, small cell lung cancer, biliary tract cancer, and non-small cell lung cancer. For more information please consult the product for Imfinzi on the EMA website.

Jemperli (dostarlimab): extension of indication to include, in combination with carboplatin and paclitaxel, the treatment of adult patients with mismatch repair deficient (dMMR)/ microsatellite instability-high (MSI-H) primary advanced or recurrent endometrial cancer (EC) and who are candidates for systemic therapy.

Jemperli was already authorised for the second-line treatment of the same subtype of endometrial cancer. For more information please consult the product for Jemperli on the EMA website.

Keytruda (pembrolizumab): extension of indication to include, in combination with fluoropyrimidine and platinum-containing chemotherapy, the first-line treatment of locally advanced unresectable or metastatic HER2-negative gastric or gastro-oesophageal junction adenocarcinoma in adults whose tumours express PD-L1 with a CPS ≥ 1.

Keytruda was already authorised for the treatment of various types of cancer, including HER2-positive gastric or gastro-oesophageal junction (GEJ) adenocarcinoma in adults whose tumours express PD-L1 with a CPS ≥ 1. Last month, Keytruda received a positive CHMP opinion for the adjuvant treatment of adults with non-small cell lung carcinoma who are at high risk of recurrence following complete resection and platinum-based chemotherapy. European commission (EC) decision is pending. For more information please consult the product for Keytruda on the EMA website.

Praluent (alirocumab): extension of indication to the treatment of paediatric patients 8 years of age and older with heterozygous familial hypercholesterolaemia (HeFH) as an adjunct to diet, in combination with a statin, or statin with other lipid lowering therapies in patients unable to reach LDL-C goals with the maximum tolerated dose of a statin or, alone or in combination with other lipid-lowering therapies in patients who are statin-intolerant, or for whom a statin is contraindicated.

Praluent was already authorised for the treatment of adults with primary hypercholesterolaemia (heterozygous familial and non-familial), mixed dyslipidaemia, or with established atherosclerotic cardiovascular disease. For more information please consult the product for Praluent on the EMA website.

Prevymis (letermovir): extension of indication to include prophylaxis of CMV disease in CMV-seronegative adults who have received a kidney transplant from a CMV-seropositive donor [D+/R-].

Prevymis was already authorised for the prophylaxis of CMV reactivation and disease in CMV-seropositive recipients [R+] of an allogeneic haematopoietic stem cell transplant. For more information please consult the product for Prevymis on the EMA website.

Rubraca (rucaparib): extension of indication to include, as monotherapy, the maintenance treatment of adult patients with advanced (FIGO Stages III and IV) high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) following completion of first-line platinum-based chemotherapy.

Rubraca was already authorised for the maintenance treatment of the same cancer types in patients who are in response to an ongoing platinum-based chemotherapy. For more information please consult the product for Rubraca on the EMA website.

Veyvondi (vonicog alfa): extension of indication to include the prevention of haemorrhage or surgical bleeding in adults (age 18 years and older) with von Willebrand disease (VWD), when desmopressin (DDAVP) treatment alone is ineffective or contraindicated.

Veyvondi was already authorised for the treatment of haemorrhage or surgical bleeding in the same patient population. For more information please consult the product for Veyvondi 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:

Apretude (capotegravir): is indicated in combination with safer sex practices for pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 infection in high-risk adults and adolescents, weighing at least 35 kg. EPAR Apretude.

Enrylaze (crisantaspase): is indicated as a component of a multi-agent chemotherapeutic regimen for the treatment of acute lymphoblastic leukaemia (ALL) and lymphoblastic lymphoma (LBL) in adult and paediatric patients (1 month and older) who developed hypersensitivity or silent inactivation to E. coli-derived asparaginase. EPAR Enrylaze.

Litfulo (ritlecitinib tosilate): is indicated for the treatment of severe alopecia areata in adults and adolescents 12 years of age and older. EPAR Litfulo.

Lyfnua (gefapixant): is indicated in adults for the treatment of refractory or unexplained chronic cough. EPAR Lyfnua.

Orserdu (elacestrant): monotherapy is indicated for the treatment of postmenopausal women, and men, with estrogen receptor (ER)-positive, HER2-negative, locally advanced or metastatic breast cancer with an activating ESR1 mutation who have disease progression following at least one line of endocrine therapy including a CDK 4/6 inhibitor. EPAR Orserdu.

Talvey (talquetamab): is indicated as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, who have received at least 3 prior therapies, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody and have demonstrated disease progression on the last therapy. EPAR Talvey.

Tepkinly (epcoritamab): as monotherapy is indicated for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic therapy. EPAR Tepkinly.

Tevimbra (tislelizumab): as monotherapy is indicated for the treatment of adult patients with unresectable, locally advanced or metastatic oesophageal squamous cell carcinoma after prior platinum-based chemotherapy. EPAR Tevimbra.

Recently started procedures:

Avacincaptad pegol - is indicated for the treatment of adults with geographic atrophy (GA) secondary to age-related macular degeneration (AMD)
Crovalimab - treatment of paroxysmal nocturnal haemoglobinuria
Dasiglucagon - treatment of severe hypoglycemia in patients with diabetes
Delgocitinib - treatment of moderate to severe chronic hand eczema (CHE)
Donanemab - to slow disease progression in adult patients with Alzheimer’s disease (AD).
Fruquintinib – Treatment of metastatic colorectal cancer. Fruquintinib is an orally available inhibitor of vascular endothelial growth factor receptors (VEGFRs) 1, 2, and 3.
Givinostat - treatment of Duchenne muscular dystrophy (DMD)
In vitro diagnostic medical device - detection of HER2 antigen
In vitro diagnostic medical device - detection of PD-L1 protein.
In vitro diagnostic medical device - immunohistochemical assay utilising an anti-PDL1 monoclonal primary antibody
In vitro diagnostic medical device - in vitro diagnostic device for laboratory use, intended for the qualitative detection of BRAF V600 mutations in DNA extracted from formalinfixed, paraffin-embedded human tissue.
Liquid ethanolic extract 30 per cent (w/w) of allium cepa fresh bulb and citrus limon fresh fruit / dry aqueous extract of paullinia cupana seed / dry hydroethanolic extract of theobroma cacao seed - treatment of alopecia areata in children and adolescents
Lutetium (177Lu) chloride - radiolabelling of carrier molecules, which have been specifically developed for radiolabelling with this radionuclide.
Macitentan / tadalafil - treatment of pulmonary arterial hypertension (PAH) in adult patients
Meningococcal group a, b, c, w and y vaccine - indicated for active immunisation to prevent invasive disease caused by Neisseria meningitidis groups A, B, C, W, and Y
Odronextamab – Orphan – Treatment of blood cancers (follicular lymphoma (FL) or diffuse large B cell lymphoma (DLBCL) and large cell lymphoma).
Single-stranded 5' capped mRNA encoding the respiratory syncytial virus glycoprotein f stabilized in the prefusion conformation – OPEN - Prevention of lower respiratory tract disease (LRTD) and acute respiratory disease (ARD) caused by respiratory syncytial virus (RSV)
Vilobelimab - treatment of adult patients with SARS-CoV-2 induced septic acute respiratory distress syndrome (ARDS) receiving invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO).
Zapomeran - active immunisation to prevent COVID-19
Zolbetuximab – Orphan – Treatment of locally advanced unresectable or metastatic HER2 negative gastric or gastro-oesophageal junction (GEJ) adenocarcinoma.
Zoonotic influenza vaccine (H5N1) (surface antigen, inactivated, adjuvanted) - active immunisation against H5 subtype of Influenza A virus