CHMP Meeting Highlights July 2023

CHMP Monthly News | 01/08/2023

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

Active immunisation against respiratory syncytial virus (RSV)
Acute lymphoblastic leukaemia
Acute myeloid leukaemia
Alopecia areata
Breast cancer
Chronic cough
Diffuse large B-cell lymphoma
Lymphoblastic lymphoma
Multiple myeloma
Oesophageal squamous cell carcinoma
Passive protection against lower respiratory tract disease caused by RSV
Reduce the risk of sexually acquired HIV-1 infection

New medicines recommended for approval:

Abrysvo (Respiratory syncytial virus vaccine): received a positive opinion for the:

Passive protection against lower respiratory tract disease (LRTD) caused by respiratory syncytial virus (RSV) in infants from birth through 6 months of age following maternal immunisation during pregnancy;
Active immunisation of individuals 60 years of age and older for the prevention of LRTD caused by RSV.

RSV is a single-stranded RNA virus that causes the majority of cases of respiratory hospitalization in infants. In adults over 65 years of age, approximately 15% of acute respiratory infections due to RSV lead to hospitalisation. LRTD is characterised by bronchiolitis and pneumonia and it is potentially life-threatening. Abrysvo is a protein-based vaccine that consists of F glycoprotein ectodomains of RSV A and B, expressed in genetically engineered Chinese Hamster Ovary cell lines. There is a particularity of Abrysvo: at variance with other vaccines, the goal of the immunization of pregnant women is the protection not of the mother but of the child who will transplacentally receive the antibodies the mother’s immune system produces against RSV. For more information please consult the product for Abrysvo on the EMA website.

Apretude (cabotegravir): received a positive opinion from CHMP 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.

HIV-1 is a retrovirus that causes infection in humans, leading to a progressive failure of the immune system if the infection progresses. Immunocompromised patients are susceptible of contracting life-threatening infections and of developing cancer. Without treatment, an infection with HIV-1 can lead to the development of the acquired immunodeficiency syndrome (AIDS) and subsequent death. Although viral replication can be successfully suppressed by antiretroviral therapy (ART), some patients develop resistance to available therapies. By binding to the integrase active site, Apretude blocks the strand transfer step of DNA integration, key to the viral replication cycle. For more information please consult the product for Apretude on the EMA website.

Enrylaze (crisantaspase): received a positive opinion for the treatment, as a component of a multi-agent chemotherapeutic regimen, 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 Escherichia coli-derived asparaginase.

LBL, an aggressive non-Hodgkin lymphoma, and ALL are blood cancers characterised by production of large amounts of immature lymphocytes by the blood marrow. ALL and LBL cancer cells are unable to synthesize asparagine, since they lack the necessary enzyme and, therefore, require exogenous sources of asparagine for their survival. Enrylaze is a recombinant form of the enzyme asparaginase, which catalyzes the conversion of L-asparagine into L-aspartic acid. Immunological reactions against previously approved products with asparaginase produced in E. coli may make these unsuitable for some patients. Enrylaze is a recombinant form of the asparaginase produced in Pseudomonas fluorescens and thus allows the treatment of patients who cannot be treated with Escherichia coli-derived asparaginase. For more information please consult the product for Enrylaze on the EMA website.

Inaqovi (decitabine / cedazuridine): received a positive opinion for the treatment, as monotherapy, of adult patients with newly diagnosed acute myeloid leukaemia (AML) who are ineligible for standard induction chemotherapy.

AML is a cancer of the white blood cells characterised by the overproduction of immature myeloid cells.

Inaqovi is a fixed-dose combination of the known active substance decitabine and the new active substance cedazuridine intended for oral administration. Decitabine is an antimetabolite (cytidine analogue), authorised in the EU since 2012 as Dacogen for the treatment of adult patients with newly diagnosed de novo or secondary acute myeloid leukaemia (AML), according to the World Health Organisation (WHO) classification, who are not candidates for standard induction chemotherapy. Dacogen is intended for intravenous administration.

Cedazuridine is a novel cytidine deaminase inhibitor that reduces the hepatic first-pass degradation of decitabine. The enhanced oral availability allows the treatment of patients with tablets (containing both decitabine and cedazuridine) inszead of repeated decitabine infusions. For more information please consult the product for Inaqovi on the EMA website.

Litfulo (ritlecitinib): received a positive opinion for the treatment of severe alopecia areata (AA) in adults and adolescents 12 years of age and older. AA is an autoimmune disease that causes hair loss in some or all areas of the body, with an average onset between 25 and 35 years of age. Although the pathophysiology of AA is complex and not fully understood, the initiation of the disease seems to be driven by cytotoxic T-cells. This cascade can be blocked by inhibiting the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway. Litfulo is a selective irreversible covalent inhibitor of JAK3 and TEC family of protein kinases. Litfulo lacks activity against JAK1/2, thereby avoiding the clinical repercussions stemming from JAK1/2 inhibition. For more information please consult the product for Litfulo on the EMA website.

Lyfnua (gefapixant): received a positive opinion for the treatment of refractory or unexplained chronic cough (UCC) in adults. Cough is a protective reflex to prevent aspiration into the lung and clear the throat and it has recently been considered as a clinical entity and not only as a symptom. Although the epidemiology of UCC is not well understood, the estimated prevalence is 4 to 11%. Lyfnua is a selective reversible P2X3 receptor antagonist, although it also has activity against the P2X2/3 receptor subtype. These receptors are ATP-gated ion channels and are involved in several physiological and pathological functions including cough, since ATP released in airway tissue triggers certain protective reflex responses via its interaction with these receptors. For more information please consult the product for Lyfnua on the EMA website.

Orserdu (elacestrant): received a positive opinion for the treatment, as monotherapy, 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.

Breast cancer is the leading cause of cancer and cancer deaths in women worldwide. Mutation in the ESR1 (estrogen receptor 1) gene are common acquired mutations that confer resistance to endocrine therapy. Orserdu is the first orally available, selective antiestrogen, an antagonist of the ER, or selective ER degrader (SERD), active also against mutated ERs. For more information please consult the product for Orserdu on the EMA website.

Talvey (talquetamab): received a positive opinion for a conditional marketing authorisation (CMA) for the treatment, as monotherapy, 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.

MM is a type of blood cancer characterized by the malignant proliferation of plasma cells. Talvey is a bispecific antibody that targets CD3, present on the surface of T-cells, and GPRC5D, a G protein–coupled receptor of unknown function but highly expressed in multiple myeloma cells. Talvey binds CD3, thereby eliciting recruitment of effector T-cells. Upon concurrent binding with GPRC5D, T-cell activation occurs, resulting in T-cell-mediated B-cell lysis. Talvey is the first therapy for the treatment of cancer targeting GPRC5D. For more information please consult the product for Talvey on the EMA website.

Tepkinly (epcoritamab): received a positive opinion for a conditional marketing authorisation (CMA) for the treatment, as monotherapy, of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic therapy.

DLBCL is an aggressive cancer of the B-lymphocytes and it is the most common form of non-Hodgkin lymphoma. As many mature B-cell lymphomas, DLBCL express the surface antigen CD20. Tepkinly is a bispecific antibody that targets CD20 and CD3, a subunit of the T-cell receptor complex. Tepkinly binds CD3, thereby eliciting recruitment of effector T-cells. Upon concurrent binding with CD20, T-cell activation occurs, resulting in T-cell-mediated B-cell lysis. For more information please consult the product for Tepkinly on the EMA website.

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

Although oesophageal cancer is a rare disease in Europe, it is one of the most common cancers worldwide and it remains highly fatal. Tevimbra 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, Tevimbra 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 Tevimbra on the EMA website.

Recommendations on extensions of therapeutic indication:

Bylvay (odevixibat): extension of indication to the treatment of cholestatic pruritus in Alagille syndrome in patients aged 6 months or older. Bylvay was already authorised for the treatment of progressive familial intrahepatic cholestasis. For more information please consult the product for Bylvay on the EMA website.

Olumiant (baricitinib): extension of indication to the treatment of active juvenile idiopathic arthritis in patients 2 years of age and older who have had an inadequate response or intolerance to one or more prior conventional synthetic or biologic disease-modifying antirheumatic drugs (DMARDs):

Polyarticular juvenile idiopathic arthritis (polyarticular rheumatoid factor positive or negative, extended oligoarticular),
Enthesitis related arthritis, and
Juvenile psoriatic arthritis.

Baricitinib may be used as monotherapy or in combination with methotrexate. Olumiant was already authorised for the treatment rheumatoid arthritis, atopic dermatitis and alopecia areata. For more information please consult the product for Olumiant on the EMA website.

Ervebo (Ebola Zaire Vaccine [rVSV∆G-ZEBOV-GP, live]): extension of indication to the active immunisation of individuals 1 year of age or older to protect against Ebola Virus Disease caused by Zaire Ebola virus. Ervebo was already authorised in patients 18 years of age and older. For more information please consult the product for Ervebo on the EMA website.

Evrysdi (risdiplam): extension of indication to the treatment of 5q spinal muscular atrophy (SMA) in patients with a clinical diagnosis of SMA Type 1, Type 2 or Type 3 or with one to four SMN2 copies. Evrysdi was already authorised in patients 2 months of age and older. For more information please consult the product for Evrysdi on the EMA website.

Foclivia (pandemic influenza vaccine [H5N1] [surface antigen, inactivated, adjuvanted]): Extension of indication to include children from 6 months to less than 18 years of age for the prophylaxis of influenza in an officially declared pandemic situation. For more information please consult the product for Foclivia on the EMA website.

Keytruda (pembrolizumab): extension of indication for the first-line treatment, in combination with trastuzumab, fluoropyrimidine and platinum-containing chemotherapy, of locally advanced unresectable or metastatic HER2-positive 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 melanoma, non-small cell lung carcinoma, classical Hodgkin lymphoma, urothelial carcinoma, head and neck squamous cell carcinoma, renal cell carcinoma, colorectal cancer, oesophageal carcinoma, breast cancer, endometrial carcinoma, cervical cancer and several microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) cancers. For more information please consult the product for Keytruda on the EMA website.

Opdivo (nivolumab): extension of indication to the adjuvant treatment, as monotherapy, of adults and adolescents 12 years of age and older with Stage IIB or IIC melanoma, or melanoma with involvement of lymph nodes or metastatic disease who have undergone complete resection. This adds the treatment of stage IIB and IIC melanoma to the existing indication. Opdivo was furthermore already authorised for the treatment of melanoma, non-small cell lung cancer, malignant pleural mesothelioma, renal cell carcinoma, classical Hodgkin lymphoma, squamous cell cancer of the head and neck, urothelial carcinoma, colorectal cancer, oesophageal squamous cell carcinoma, and gastric, gastro-oesophageal junction and oesophageal adenocarcinoma. For more information please consult the product for Opdivo on the EMA website.

Spikevax bivalent Original/Omicron BA.4-5 (elasomeran / imelasomeran and elasomeran / davesomeran and elasomeran / COVID-19 mRNA vaccine [nucleoside-modified]): extension of indication to the active immunisation to prevent COVID-19 caused by SARS-CoV-2 in individuals 6 months of age and older. Previously, Spikevax bivalent Original/Omicron BA.4-5 was authorised in individuals 6 years of age and older and only after receiving at least a primary vaccination course against COVID-19. For more information please consult the product for Spikevax bivalent Original/Omicron BA.4-5 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:

Briumvi (ublituximab): is indicated for the treatment of adult patients with relapsing forms of multiple sclerosis with active disease defined by clinical or imaging features. EPAR Briumvi.

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

Lytgobi (futibatinib): monotherapy is indicated for the treatment of adult patients with locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or rearrangement that have progressed after at least one prior line of systemic therapy. EPAR Lytgobi.

Opfolda (miglustat): is an enzyme stabiliser of cipaglucosidase alfa long-term enzyme replacement therapy in adults with late-onset Pompe disease (acid α-glucosidase deficiency). EPAR Opfolda.