CHMP Meeting Highlights September 2022

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

• Acromegaly
• Haemolytic anaemia in cold agglutinin disease
• Cytomegalovirus infection or disease
• Diffuse large B-cell lymphoma
• High-grade B-cell lymphoma
• Prevention of Respiratory Syncytial Virus (RSV) lower respiratory tract disease
• Pyruvate kinase deficiency

New medicines recommended for approval:

Beyfortus (nirsevimab): for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease (LRTD) in neonates and infants during their first RSV season. RSV is a single-stranded RNA virus that causes the majority of cases of respiratory hospitalisation in infants. LRTD is characterised by bronchiolitis and pneumonia and it is potentially life-threatening, specially during the first 6 months of life. Beyfortus is a monoclonal antibody targeted against the viral F surface protein, which is required for the fusion between the virus particle and the host cell. For more information, see the EMA news announcement on Beyfortus. For more information please consult the product for Beyfortus on the EMA website.

Enjaymo (sutimlimab): for the treatment of haemolytic anaemia in adult patients with cold agglutinin disease (CAD). CAD is a rare autoimmune disease characterised by the presence at high concentrations of autoantibodies (usually IgMs) that target red blood cells (RBCs). These autoantibodies, or cold agglutinins, bind to RBCs causing their agglutination and haemolysis, mainly through activation of the classical pathway of the complement system. This is exacerbated at cold temperatures. Enjaymo is a first-in-class monoclonal antibody that targets the complement component 1s (C1s), thereby blocking the classical complement pathway cascade. For more information please consult the product for Enjaymo on the EMA website.

Livtencity (maribavir): for the treatment of cytomegalovirus (CMV) 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 (HSCT) or solid organ transplant (SOT). CMV is a double-stranded DNA virus of the herpesvirus family. Although a primary CMV infection is common early in life, it usually curses as asymptomatic or self-limiting in immunocompetent patients, in which reactivation is uncommon. However, a CMV infection can become serious in immunocompromised individuals, such as after undergoing HSCT or SOT. Furthermore, resistance to available therapies is increasing, which translates into limited treatment options in this patient population. Livtencity is administered orally and it inhibits viral replication by competitively inhibiting the viral pUL97 protein kinase. For more information please consult the product for Livtencity on the EMA website.

Mycapssa (octreotide): for maintenance treatment in adult patients with acromegaly who have responded to and tolerated treatment with somatostatin analogues. Acromegaly is a rare life-threatening disease characterised by increased growth hormone (GH) secretion after the growth plates have closed, which results in excessive growth of body tissues. This over-production of GH is most often caused by an adenoma of the anterior pituitary gland. Mycapssa is an orally-available prolonged-duration synthetic derivative of somatostatin, the growth hormone-inhibiting hormone, that inhibits the increased release of GH from the pituitary gland. For more information please consult the product for Mycapssa on the EMA website.

Pyrukynd (mitapivat): for the treatment of pyruvate kinase deficiency (PK deficiency) in adult patients. PK deficiency is a genetic metabolic disorder caused by mutations in the PKLR gene, which lead to deficiency of the glycolytic enzyme pyruvate kinase. PK converts phosphoenolpyruvate (PEP) to pyruvate in the last step of the glycolysis, thereby generating half of the ATP in erythrocytes. A PK deficiency leads to insufficient ATP in the RBCs, which brings cellular processes to a halt. Although the presentation of the disease is very heterogeneous, a common clinical symptom is haemolytic anaemia. Pyrukynd binds and allosterically activates pyruvate kinase, increasing its affinity for PEP, thereby enhancing the glycolytic pathway. For more information please consult the product for Pyrukynd on the EMA website.

Zynlonta (loncastuximab tesirine): received a positive opinion for a conditional marketing authorisation (CMA) for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma (HGBL), 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. HGBL is another aggressive type of B-cell non-Hodgkin lymphoma.

Zynlonta is an antibody-drug conjugate that binds CD19 on the cell surface, forming a complex that is subject to endocytosis. The cleavage of Zynlonta within the lysosomes releases the drug portion of the conjugate, the pyrrolobenzodiazepine dimer cytotoxin tesirine, which binds to and cross-links DNA, thereby stalling DNA replication and blocking cell division, ultimately leading to cell death. CD19 is a transmembrane glycoprotein normally expressed in cells of the B lineage and its expression is kept in B-cell malignancies, such as DLBCL and HGBL. For more information please consult the product for Zynlonta on the EMA website.

Recommendations on extensions of therapeutic indication:

Adtralza (tralokinumab): extension of indication to include the treatment of moderate-to-severe atopic dermatitis in adolescent patients 12 years and older who are candidates for systemic therapy. Adtralza was already authorised in adults. For more information please consult the product for Adtralza on the EMA website.

Biktarvy (bictegravir / emtricitabine / tenofovir alafenamide): extension of indication to include the treatment of human immunodeficiency virus-1 (HIV-1) infection in paediatric patients at least 2 years of age and weighing at least 14 kg without present or past evidence of viral resistance to the integrase inhibitor class, emtricitabine or tenofovir. Biktarvy was already authorised in adults. For more information please consult the product for Biktarvy on the EMA website.

Brukinsa (zanubrutinib): extension of indication to include the treatment, as monotherapy, of adult patients with marginal zone lymphoma who have received at least one prior anti-CD20-based therapy. Brukinsa was already authorised for the treatment of Waldenström’s macroglobulinaemia. For more information please consult the product for Brukinsa on the EMA website.

Evusheld (tixagevimab / cilgavimab): extension of indication to include the treatment of adults and adolescents (aged 12 years and older weighing at least 40 kg) with COVID-19, who do not require supplemental oxygen and who are at increased risk of progressing to severe COVID-19. Evusheld was already authorised for the pre-exposure prophylaxis of COVID-19. For more information please consult the product for Evusheld on the EMA website.

Exparel liposomal (bupivacaine): extension of indication to include the treatment of children aged 6 years or older as a field block for treatment of somatic post-operative pain from small- to medium-sized surgical wounds. Exparel liposomal was already authorised in adults for the same indication and for the treatment of post-operative pain. For more information please consult the product for Exparel on the EMA website.

Revolade (eltrombopag): extension of indication to the treatment of adults with primary immune thrombocytopenia (ITP) lasting 6 months or longer from diagnosis and who are refractory to other treatments (e.g. corticosteroids, immunoglobulins). Revolade was already authorised in this indication in paediatric patients aged 1 year and older. Furthermore, Revolade was already authorised for the treatment of acquired severe aplastic anaemia and for the treatment of thrombocytopenia in patients with chronic hepatitis C virus infection. For more information please consult the product for Revolade on the EMA website.

Skyrizi (risankizumab): extension of indication to include the treatment of adult patients with moderately to severely active Crohn's disease who have had an inadequate response to, lost response to, or were intolerant to conventional therapy or a biologic therapy. Skyrizi was already authorised for the treatment of plaque psoriasis and psoriatic arthritis in adults. For more information please consult the product for Skyrizi on the EMA website.

Vaxneuvance (pneumococcal polysaccharide conjugate vaccine [15-valent, adsorbed]): extension of indication to the active immunisation for the prevention of invasive disease, pneumonia and acute otitis media caused by Streptococcus pneumoniae in infants, children and adolescents from 6 weeks to less than 18 years of age. Vaxneuvance was already authorised for the active immunisation for the prevention of invasive disease and pneumonia caused by S. pneumoniae in adults. For more information please consult the product for Vaxneuvance on the EMA website.

Veklury (remdesivir): extension of indication to the treatment of coronavirus disease 2019 (COVID-19) in:

1. paediatric patients (at least 4 weeks of age and weighing at least 3 kg) with pneumonia requiring supplemental oxygen (low or high flow oxygen or other non-invasive ventilation at start of treatment);
2. paediatric patients (weighing at least 40 kg) who do not require supplemental oxygen and who are at increased risk of progressing to severe COVID-19.

Veklury was already authorised for the treatment of adults and adolescents for indication (1) and for adults only for indication (2). For more information please consult the product for Veklury on the EMA website.

Xalkori (crizotinib): extension of indication to include the treatment of paediatric patients (age ≥6 to <18 years) with:

• relapsed or refractory systemic anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma;
• recurrent or refractory (ALK)-positive unresectable inflammatory myofibroblastic tumour.

Xalkori was already authorised for the treatment of non-small cell lung cancer in adults. For more information please consult the product for Xalkori on the EMA website.

Yescarta (axicabtagene ciloleucel): extension of indication to the treatment of adult patients with diffuse large B-cell lymphoma and high-grade B-cell lymphoma that relapses within 12 months from completion of, or is refractory to, first-line chemoimmunotherapy. Yescarta was already authorised for the treatment of relapsed or refractory diffuse large B-cell lymphoma, primary mediastinal large B-cell lymphoma and follicular lymphoma. For more information please consult the product for Yescarta 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:

Kinpeygo (budesonide): is indicated for the treatment of primary immunoglobulin A nephropathy in adults at risk of rapid disease progression with a urine protein-to-creatinine ratio (UPCR) ≥1.5 g/gram. EPAR Kinpeygo.

Nexviadyme (avalglucosidase alfa): is indicated for long-term enzyme replacement therapy for the treatment of patients with Pompe disease (acid α-glucosidase deficiency). EPAR Nexviadyme.

Opdualag (relatlimab / nivolumab): is indicated for the first-line treatment of advanced (unresectable or metastatic) melanoma in adults and adolescents 12 years of age and older with tumour cell PD-L1 expression <1 %. EPAR Opdualag.

Pepaxti (melphalan flufenamide): is indicated, in combination with dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least three prior lines of therapies, whose disease is refractory to at least one proteasome inhibitor, one immunomodulatory agent, and one anti-CD38 monoclonal antibody, and who have demonstrated disease progression on or after the last therapy. For patients with a prior autologous stem cell transplantation, the time to progression should be at least 3 years from transplantation. EPAR Pepaxti.

Roctavian (valoctocogene roxaparvovec): is indicated for the treatment of severe haemophilia A (congenital factor VIII deficiency) in adult patients without a history of factor VIII inhibitors and without detectable antibodies to adeno-associated virus serotype 5 (AAV5). EPAR Roctavian.

Scemblix (asciminib): is indicated for the treatment of adult patients with Philadelphia chromosome-positive chronic myeloid leukaemia in chronic phase previously treated with two or more tyrosine kinase inhibitors. EPAR Scemblix.

Sunlenca (lenacapavir): injection, in combination with other antiretroviral(s), is indicated for the treatment of adults with multidrug resistant HIV-1 infection for whom it is otherwise not possible to construct a suppressive anti-viral regimen. EPAR Sunlenca.

Upstaza (eladocagene exuparvovec): is indicated for the treatment of patients aged 18 months and older with a clinical, molecular, and genetically confirmed diagnosis of aromatic L-amino acid decarboxylase deficiency with a severe phenotype. EPAR Upstaza.

Vyvgart (efgartigimod alfa): is indicated as an add-on to standard therapy for the treatment of adult patients with generalised Myasthenia Gravis who are anti-acetylcholine receptor antibody positive. EPAR Vyvgart.

Xenpozyme (olipudase alfa): is indicated as an enzyme replacement therapy for the treatment of non-Central Nervous System manifestations of Acid Sphingomyelinase Deficiency in paediatric and adult patients with type A/B or type B. EPAR Xenpozyme.

Zokinvy (lonafarnib): is indicated for the treatment of patients 12 months of age and older with a genetically confirmed diagnosis of Hutchinson-Gilford progeria syndrome or a processing-deficient progeroid laminopathy associated with either a heterozygous LMNA mutation with progerin-like protein accumulation or a homozygous or compound heterozygous ZMPSTE24 mutation. EPAR Zokinvy.

Recently started procedures:

• Adagrasib - Treatment of patients with advanced non-small cell lung cancer with KRAS G12C mutation.
• Ferumoxytol - Intravenous treatment of iron deficiency anaemia.
• Futibatinib - Orphan - Treatment of cholangiocarcinoma.
• Glofitamab - Orphan - Treatment of diffuse large B-cell lymphoma.
• Mirikizumab - Treatment of moderately to severely active ulcerative colitis.
• Niraparib tosylate monohydrate / abiraterone acetate - Treatment of adult patients with prostate cancer.
• Oteseconazole - Treatment and prevention of recurrent vulvovaginal candidiasis including the acute episodes of RVVC in adult women.
• Polihexanide - Orphan - Treatment of acanthamoeba keratitis.
• SARS-CoV-2 virus - beta-propiolactone inactivated - Active immunization against coronavirus disease 2019.

Other topics of interest:

Update on the following authorised medicines for the treatment or prevention of COVID-19:

The CHMP recommended extending the use of Nuvaxovid (COVID-19 Vaccine [recombinant, adjuvanted]) as a booster in adults who have previously received Nuvaxovid.

The CHMP has recommended the authorisation of two adapted mRNA vaccines, Comirnaty Original/Omicron BA.1 and Spikevax bivalent Original/Omicron BA.1, intended for the immunisation against COVID-19 in people aged 12 years and above who have received at least primary vaccination against COVID-19. These vaccines target the Omicron BA.1 subvariant in addition to the original strain. Please see the EMA news announcement on Comirnaty and Spikevax.

The CHMP recommended the authorisation of the adapted bivalent mRNA vaccine Comirnaty Original/Omicron BA.4-5 for use in people aged 12 years and above who have received at least a primary course of vaccination against COVID-19. This vaccine is an adapted version that targets the Omicron subvariants BA.4 and BA.5 in addition to the original strain of SARS-CoV-2. For more information, please see the EMA news announcement on Comirnaty.

Additionally, the CHMP recommended the authorisation of Comirnaty as a booster in children from 5 to 11 years of age.

Furthermore, Comirnaty and Spikevax have been recommended for a switch from CMA to standard authorisation. After receiving a conditional marketing authorisation, the CHMP has now recommended granting a full marketing authorisation to these vaccines, following the submission of data that fulfils the outstanding specific obligations. For more information, please see the EMA news announcement on Comirnaty's and Spikevax's switch to standard marketing authorisation.

Previous CHMP Meeting Highlights can be accessed at: https://www.basg.gv.at/en/healthcare-professionals/chmp-highlights

Further inquiry note

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