CHMP Meeting Highlights June 2022
This month, medicinal products for the following indications have received a positive opinion:
- Active immunisation against COVID-19
- Haemophilia A
- HIV-1 infection
- Multiple myeloma
- Myasthenia Gravis
- Myeloid leukaemia
New medicines recommended for approval:
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.
MM is an incurable blood cancer characterized by the malignant proliferation of plasma cells and the overexpression of a monoclonal immunoglobulin protein. Symptoms include bone pain and fractures, infections and renal insufficiency.
Melphalan is a phenylalanine derivative of nitrogen mustard that acts as a DNA-alkylating agent with broad antitumor effects. Although it was first authorised in Canada in 1963 and has been authorised in several EU member states since then, melphalan was first centrally authorised in the EU in 2020 under the commercial name Phelinun, for the treatment of MM, amongst other. Melphalan flufenamide (melflufen) is a lipophilic peptide-drug conjugate of melphalan. Its lipophilic nature allows for an increased diffusion across cell membranes. Once inside the cell, the aminopeptidase-mediated peptide hydrolysis releases the alkylating moiety, which accumulates within the cell inducing DNA damage and subsequent apoptosis. For more information please consult the product for Pepaxti on the EMA website.
Rayvow (lasmiditan): is indicated for the acute treatment of the headache phase of migraine attacks, with or without aura in adults.
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.
Rayvow belongs to the serotonin 1F (5-HT1F) receptor agonists, also known as ditans. By activating 5-HT1F receptor, Rayvow blocks the release of CGRPs, thereby preventing the development of the cascade of events that result in a migraine attack. Due to its high affinity to the 1F receptor, Rayvow does not cause vasoconstriction. For more information please consult the product for Rayvow on the EMA website.
Roctavian (valoctocogene roxaparvovec): received a positive opinion for a conditional marketing authorisation (CMA) 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).
Congenital haemophilia is an X-linked recessive disease caused by mutations in the genes coding for the coagulation factor VIII (haemophilia A) or IX (haemophilia B). It is characterised by the inability to form blood clots, which results in a higher risk of bruising, internal bleeding and bleeding inside the joints. The disease can be classified as mild, moderate or severe, depending on the endogenous plasma activity levels of clotting factors. Patients who are treated with anti-haemophilic factors to replace the deficient coagulation factor can develop anti-factor VIII or IX alloantibodies (inhibitors), which neutralise the activity of the administered replacement factors.
Roctavian is a AAV5 vector that encodes FVIII under the control of a liver-specific promoter. Roctavian is designed for prolonged expression and is, therefore, delivered by a single intravenous dose. EMA news announcement for Roctavian. For more information please consult the product for Roctavian on the EMA website.
Scemblix (asciminib): is indicated for the treatment of adult patients with Philadelphia chromosome-positive chronic myeloid leukaemia in chronic phase (Ph+ CML-CP) previously treated with two or more tyrosine kinase inhibitors.
CML is a cancer of the white blood cells characterised by the overproduction of immature myeloid cells and mature granulocytes. It is usually associated with the Philadelphia (Ph) chromosome, an abnormality of chromosome 22 involving a reciprocal translocation between chromosome 9 and 22, which results in a fusion gene called BCR-ABL1. This fusion gene encodes a chimeric tyrosine kinase with a constitutively active ABL1 domain, which causes uncontrollable division by disrupting the normal cell cycle. CML can be controlled in its chronic phase by administering tyrosine kinase inhibitors (TKIs). However, some patients develop resistance, tolerability or loss of response to these therapies.
Scemblix is an inhibitor of the BCR-ABL1 kinase activity, targeting a different binding site (the myristoyl pocket) than the other authorised TKIs, which target the ATP binding site of BCR-ABL1. For more information please consult the product for Scemblix on the EMA website.
Sunlenca (lenacapavir): is indicated, in combination with other antiretroviral(s), for the treatment of adults with multidrug-resistant human immunodeficiency virus 1 (HIV-1) infection for whom it is otherwise not possible to construct a suppressive anti-viral regimen. Sunlenca tablet is indicated for oral loading prior to administration of long-acting Sunlenca injection.
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 viral capsid, Sunlenca interferes with essential viral lifecycle steps, thereby inhibiting HIV-1 replication. For more information please consult the product for Sunlenca on the EMA website.
Valneva (COVID-19 vaccine (inactivated, adjuvanted, adsorbed)): is indicated for active immunisation to prevent COVID-19 caused by SARS-CoV-2 in individuals 18 to 50 years of age.
COVID-19 or Coronavirus disease 2019, is a contagious disease caused by the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-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.
Valneva is an inactivated viral vaccine and it is the sixth vaccine recommended in the European Union (EU) for protecting against COVID-19. EMA news announcement for Valneva. For more information please consult the product for Valneva on the EMA website.
Vyvgart (efgartigimod alfa): is indicated as an add-on to standard therapy for the treatment of adult patients with generalised Myasthenia Gravis (MG) who are anti-acetylcholine receptor (AChR) antibody positive.
MG is an autoimmune disease that causes muscle weakness. Around 90% of patients have detectable levels of autoantibodies in serum and the most common target AChR at the neuromuscular junction, leading to failure of neuromuscular transmission.
Vyvgart is a recombinant Fc fragment derived from human immunoglobulin (IgG), which binds the neonatal Fc receptor, thereby reducing the levels of circulating IgGs, including IgG autoantibodies. For more information please consult the product for Vyvgart on the EMA website.
Recommendations on extensions of therapeutic indication:
Crysvita (burosumab): extension of indication to the treatment of FGF23-related hypophosphataemia in tumour-induced osteomalacia associated with phosphaturic mesenchymal tumours that cannot be curatively resected or localised in children and adolescents aged 1 to 17 years and in adults. Crysvita was already authorised for the treatment of X-linked hypophosphataemia. For more information please consult the product for Crysvita on the EMA website.
Enhertu (trastuzumab deruxtecan): extension of indication, as monotherapy, to the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who have received one or more prior anti HER2 based regimens. Enhertu was previously authorised for patients who had received two or more prior anti HER2 based regimens. For more information please consult the product for Enhertu on the EMA website.
Imbruvica (ibrutinib): extension of indication to the treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL), in combination with venetoclax. Imbruvica was already authorised for the treatment of mantle cell lymphoma, Waldenström’s macroglobulinaemia and for the treatment of CLL as single agent or in combination with rituximab, obinutuzumab or bendamustine. For more information please consult the product for Imbruvica on the EMA website.
Lonquex (lipegfilgrastim): extension of indication to children 2 years of age and older, for the reduction in the duration of neutropenia and the incidence of febrile neutropenia in patients treated with cytotoxic chemotherapy for malignancy (with the exception of chronic myeloid leukaemia and myelodysplastic syndromes). Lonquex was already authorised in adults. For more information please consult the product for Lonquex on the EMA website.
Lynparza (olaparib): extension of indication, as monotherapy or in combination with endocrine therapy, for the adjuvant treatment of adult patients with germline BRCA1/2-mutations who have HER2-negative, high risk early breast cancer previously treated with neoadjuvant or adjuvant chemotherapy. Lynparza was already authorised for the treatment of ovarian cancer, pancreatic adenocarcinoma, prostate cancer and breast cancer. For more information please consult the product for Lynparza on the EMA website.
Nuvaxovid (COVID-19 Vaccine (recombinant, adjuvanted)): extension of indication to the active immunisation to prevent COVID-19 caused by SARS-CoV-2 in individuals 12 years of age and older. Nuvaxovid was already authorised for patients 18 years of age and older. EMA news announcement for Nuvaxovid. For more information please consult the product for Nuvaxovid on the EMA website.
Rinvoq (upadacitinib): extension of indication to the treatment of active non-radiographic axial spondyloarthritis in adult patients with objective signs of inflammation as indicated by elevated C-reactive protein and/or magnetic resonance imaging, who have responded inadequately to nonsteroidal anti-inflammatory drugs. Rinvoq was already authorised for the treatment of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and atopic dermatitis. For more information please consult the product for Rinvoq on the EMA website.
Zerbaxa (ceftolozane / tazobactam): extension of indication to the treatment of the following infections in paediatric patients: complicated intra-abdominal infections, acute pyelonephritis and complicated urinary tract infections. Zerbaxa was already authorised in adults for the treatment of these infections and of hospital-acquired pneumonia. For more information please consult the product for Zerbaxa 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:
Carvykti (ciltacabtagene autoleucel): is indicated for the treatment of adult patients with relapsed and refractory multiple myeloma, 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. EPAR Carvykti.
Lunsumio (mosunetuzumab): as monotherapy is indicated for the treatment of adult patients with relapsed or refractory follicular lymphoma who have received at least two prior systemic therapies. EPAR Lunsumio.
Recently started procedures:
- Etranacogene dezaparvovec - Orphan - Advanced therapy medicinal product (ATMP) - Treatment of adults with Haemophilia B (congenital Factor IX deficiency) and with a preexisting neutralising anti-AAV5 antibody titre below 1:700 to reduce the frequency of bleeding episodes and the need for Factor IX replacement therapy.
- Ivosidenib - Orphan - Treatment of acute myeloid leukaemia and treatment of metastatic cholangiocarcinoma.
- Tislelizumab - Orphan - Treatment of adult patients with unresectable, recurrent, locally advanced or metastatic oesophageal squamous cell carcinoma after prior chemotherapy.
- Tislelizumab - Treatment of locally advanced or metastatic non-squamous non-small cell lung cancer in adults, treatment of locally advanced or metastatic squamous non-small cell lung cancer in adults, locally advanced or metastatic non-small cell lung cancer after prior chemotherapy in adults,
- Tremelimumab - Orphan - For use in combination with durvalumab for the treatment of adults with unresectable hepatocellular carcinoma.