CHMP Meeting Highlights November 2021

Information about the Austrian representation on the CHMP and monthly updates can be found at this Link.

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

• COVID-19
• Delayed methotrexate elimination or risk of methotrexate toxicity
• Granulomatosis with polyangiitis and microscopic polyangiitis
• Growth hormone deficiency
• Migraine
• Neuromyelitis optica spectrum disorders
• Non-small cell lung cancer (with KRAS G12C mutation)
• Orthopoxvirus disease
• Weight management in obesity or overweight with other related conditions

New medicines recommended for approval:

Regkirona (regdanvimab): is indicated for the treatment of adults with coronavirus disease 2019 (COVID-19) who do not require supplemental oxygen and who are at increased risk of progressing to severe COVID-19. For more information please consult the product page for Regkirona on the EMA website.

Ronapreve (casirivimab / imdevimab): is indicated for:

• Treatment of COVID-19 in adults and adolescents aged 12 years and older weighing at least 40 kg who do not require supplemental oxygen and who are at increased risk of progressing to severe COVID-19.
• Prevention of COVID-19 in adults and adolescents aged 12 years and older weighing at least 40 kg.

COVID-19 or Coronavirus disease 2019, is a contagious disease caused by the SARS‑CoV‑2 virus (Severe acute respiratory syndrome coronavirus 2). Although this virus can infect a wide variety of cells, it is most known for causing respiratory tract symptoms, which vary from mild to severe. The virus enters the cells mainly by binding to the angiotensin converting enzyme 2 (ACE2). Regkirona and Ronapreve bind to the receptor-binding domain (RBD) of the Spike protein of the SARS‑CoV‑2 virus, thereby impeding its attachment to ACE2. This blocks the entry of the virus into the cells and hinders infection. Regkirona and Ronapreve are the first monoclonal antibodies to receive a positive opinion by the CHMP for the treatment of COVID-19. For more information please consult the product page for Ronapreve on the EMA website.

Tavneos (avacopan): is indicated, in combination with a rituximab or cyclophosphamide regimen, for the treatment of adult patients with severe, active granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). Anti-neutrophil-cytoplasmic-antibody (ANCA)-associated vasculitides (AAVs) are a group of several rare diseases that curse with systemic inflammation of small blood vessels, with the respiratory tract and the kidneys most commonly affected. GPA and MPA are the two main forms of the disease and are potentially fatal. AAVs are characterized by circulating ANCAs and neutrophil activation. Furthermore, it has been hypothesized that an involvement of the complement system is key for the development of the disease. Tavneos exerts its immunosuppressive effect by selectively blocking the binding of the complement subunit C5a to its receptor. For more information please consult the product page for Tavneoson the EMA website.

Lonapegsomatropin Ascendis Pharma (lonapegsomatropin): is indicated for the treatment of growth failure in children and adolescents aged from 3 years up to 18 years due to insufficient endogenous growth hormone secretion (growth hormone deficiency, GHD). GHD is characterised by too low levels of growth hormone, which translate into growth failure. The aetiology of GHD can be of congenital, acquired or idiopathic nature. Lonapegsomatropin is a long-acting product, constituted by human growth hormone (somatropin) conjugated to an mPEG (methoxypolyethylene glycol) carrier via a linker. Through controlled auto-cleavage of the linker, lonapegsomatropin releases its hormonal component. For more information please consult the product page for Lonapegsomatropin Ascendis Pharma the EMA website.

Lumykras (sotorasib): received a positive opinion for a conditional marketing authorisation (CMA). It is indicated as monotherapy for the treatment of adults with advanced non-small cell lung cancer (NSCLC) with KRAS G12C mutation and who have progressed after at least one prior line of systemic therapy. NSCLC is a serious and often fatal disease. KRAS-G12C is a driver mutation in many cancers and it represents about 13 % of all mutations in NSCLC. KRAS is a GTPase encoded by a proto-oncogene and the mutated KRAS-G12C is a constitutively active form of the enzyme. Lumykras binds KRAS-G12C and prevents downstream signalling by locking the mutated protein in an inactive state. For more information please consult the product page for Lumykras the EMA website.

Tecovirimat SIGA (tecovirimat): received a positive opinion for an approval under exceptional circumstances. It is indicated for the treatment of the following viral infections in adults and children with body weight at least 13 kg: smallpox, monkeypox and cowpox. It is also indicated to treat complications due to replication of vaccinia virus following vaccination against smallpox, in adults and children with body weight at least 13 kg. These viruses belong to the orthopoxvirus genus. Smallpox, which was certified globally eradicated in 1980 by the World Health Organisation, is caused by the variola virus, which is highly infectious and capable of causing epidemics very rapidly. Tecovirimat targets a highly conserved membrane protein encoded by the vaccinia virus and inhibits its interaction with cellular components. For more information please consult the product page for Tecovirimat SIGA the EMA website.

Uplizna (inebilizumab): is indicated as monotherapy for the treatment of adult patients with neuromyelitis optica spectrum disorders (NMOSD) who are anti-aquaporin 4 immunoglobulin G (AQP4-IgG) seropositive. NMOSD is a rare and chronic autoimmune syndrome of heterogeneous aetiology, which manifests with acute inflammation of the optic nerve and spinal cord. AQP4 is expressed in astrocytes and it is the most abundant water channel in the central nervous system. AQP4-IgGs are detected in 80-90% of patients and cause astrocyte loss by antibody-mediated immune responses, although the mechanism is not fully understood. Uplizna is a monoclonal antibody that binds to a specific surface antigen of the B-cells, which results in a depletion of these cells, thereby suppressing the immune response. For more information please consult the product page for Uplizna the EMA website.

Voraxaze (glucarpidase): received a positive opinion for an approval under exceptional circumstances. It is indicated to reduce toxic plasma methotrexate concentration in adults and children (aged 28 days and older) with delayed methotrexate elimination or at risk of methotrexate toxicity. MTX is a cytotoxic and immunosuppressing agent that has been used for decades, alone or in combination, for the treatment of cancer and autoimmune diseases. Elevated plasma concentrations of MTX expose multiple organs to its toxic effects. Risk factors for increased concentrations include renal dysfunction, hypovolemia, drug-drug interactions and acidic urine. Voraxaze is a recombinant enzyme that inactivates MTX by hydrolysing it into two inactive metabolites, effectively reducing MTX concentrations. These metabolites are subsequently metabolised in the liver. For more information please consult the product page for Voraxaze the EMA website.

Vyepti (eptinezumab): is indicated for the prophylaxis of migraine in adults who have at least 4 migraine days per month. Migraine is a chronic condition characterized by recurrent headaches that may affect quality of life and productivity. Although the causes of migraine are unknown, calcitonin gene-related peptides (CGRPs) have been found to be involved in the development of pain in migraine. Vyepti is an anti-CGRP monoclonal antibody that is administered intravenously. By binding to CGRP, it prevents the development of the cascade of events that result in a migraine attack. For more information please consult the product page for Vyepti the EMA website.

Wegovy (semaglutide): is indicated as an adjunct to a reduced-calorie diet and increased physical activity for weight management, including weight loss and weight maintenance, in adults with an initial Body Mass Index (BMI) of

• ≥30 kg/m2 (obesity), or
• ≥27 kg/m2 to <30 kg/m2 (overweight) in the presence of at least one weight-related comorbidity, e.g. dysglycaemia (prediabetes or type 2 diabetes mellitus), hypertension, dyslipidaemia, obstructive sleep apnoea or cardiovascular disease.

Obesity and overweight are characterised by excessive accumulation of body fat that may have a negative impact on health. The prevalence of obesity and overweight continues to increase globally in adults and children, and the risk of comorbidities increases with increasing BMI. Wegovy is an analogue of glucagon-like peptide-1 (GLP-1). By binding to the GLP-1 receptor, Wegovy triggers a downstream cascade that results in the regulation of appetite and caloric intake, amongst other. The active substance semaglutide has previously been approved for the treatment of type 2 diabetes (medicinal product Ozempic®, authorized in the EU since 2018). For more information please consult the product page for Wegovy (semaglutide) the EMA website.

Recommendations on extensions of therapeutic indication:

Dengvaxia (dengue tetravalent vaccine, live attenuated): extension of indication to the prevention of dengue disease caused by dengue virus serotypes 1, 2, 3 and 4 in individuals 6 to 45 years of age with test-confirmed previous dengue infection. For more information please consult the product for Dengvaxia on the EMA website.

Epclusa (sofosbuvir / velpatasvir): extension of indication to the treatment of chronic hepatitis C virus infection in patients 3 years of age and older. For more information please consult the product for Epclusa on the EMA website.

Kaftrio (ivacaftor / tezacaftor / elexacaftor): extension of indication to the treatment, in a combination regimen with ivacaftor, of cystic fibrosis in patients aged 6 years and older who have at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. For more information please consult the product for Kaftrio on the EMA website.

Kalydeco (ivacaftor): extension of indication to the treatment, in a combination regimen with ivacaftor / tezacaftor / elexacaftor tablets, of adults, adolescents and children aged 6 years and older with cystic fibrosis who have at least one F508del mutation in the CFTR gene. For more information please consult the product for Kalydeco on the EMA website.

Noxafil (posaconazole): extension of indication to the treatment of invasive aspergillosis that is refractory to amphotericin B or itraconazole or in patients who are intolerant to these medicinal products. It is indicated for use in paediatric patients from 2 years of age weighing more than 40 kg and adults. Noxafil is also approved for the treatment of other fungal infections in these patients. For more information please consult the product for Noxafil on the EMA website.

Rapiscan (regadenoson): the indication has been updated to:
This medicinal product is for diagnostic use only. Rapiscan is a selective coronary vasodilator for use in adults as a pharmacological stress agent for:

• myocardial perfusion imaging in patients unable to undergo adequate exercise stress.
• the measurement of fractional flow reserve (FFR) of a single coronary artery stenosis during invasive coronary angiography, when repeated FFR measurements are not anticipated.

For more information please consult the product for Rapiscan on the EMA website.

Newly published EPARs:

The EPAR (European public assessment report) is the main document where the EMA publishes the detailed information from the medicines assessed by the CHMP. Below is a list of the EPARs for recently approved products that have been made available at the EMA homepage between 08-11 November 2021:

Ronapreve (casirivimab / imdevimab): is indicated for the treatment and prevention of COVID-19 in adults and adolescents aged 12 years and older weighing at least 40 kg. EPAR Ronapreve. EPAR Ronapreve.

Recently started procedures:

• Tebentafusp - Orphan - Treatment of uveal melanoma.
• Lenacapavir - Treatment of human immunodeficiency virus type 1 (HIV-1) infection.
• Octreotide - Orphan - Treatment of acromegaly.
• Efgartigimod alfa - Orphan - Treatment of generalised Myasthenia Gravis.

Further inquiry note

basg_anfragen@basg.gv.at