CHMP Meeting Highlights February 2023
This month, medicinal products for the following indications have received a positive opinion:
- Acute myeloid leukaemia
- Anaemia associated with chronic kidney disease
- Fabry disease
- Facial angiofibroma associated with tuberous sclerosis complex
- Non-segmental vitiligo
- Prostate cancer
New medicines recommended for approval:
Akeega (niraparib / abiraterone acetate): is indicated with prednisone or prednisolone for the treatment of adult patients with metastatic castration resistant prostate cancer (mCRPC) and BRCA1/2 gene mutations (germline and/or somatic) in whom chemotherapy is not clinically indicated.
Prostate cancer is the second most common cancer in men globally and, although the overall survival for patients with localised cancer is very high, the life expectancy decreases dramatically for patients with advanced disease. Abiraterone acetate is a precursor of abiraterone, an antiandrogen that decreases testosterone synthesis by inhibiting CYP17.
Niraparib is a poly ADP ribose polymerase (PARP) inhibitor. PARPs are involved in many cellular processes including DNA repair and stability and apoptosis. Niraparib blocks DNA-associated PARPs, thereby inhibiting DNA repair and promoting the formation of double strand breaks in replicating cells. While in normal cells these can be repaired by homologous recombination, the absence of functional BRCA1/2 leads to the activation of error-prone repair pathways, ultimately leading to genome instability and cell death. For more information please consult the product for Akeega on the EMA website.
Elfabrio (pegunigalsidase alfa): is indicated for long-term enzyme replacement therapy in adult patients with a confirmed diagnosis of Fabry disease (deficiency of alpha-galactosidase). Fabry disease is a rare X-linked genetic disorder caused by mutations in the alpha-galactosidase A gene (GLA), which result in a decreased activity of the GLA enzyme. GLA is involved in many catabolic pathways, including the processing of glycoproteins and glycolipids. A reduction in its activity leads to accumulation of glycosphingolipids (mainly globotriaosylceramide, Gb3) within lysosomes in various tissues, resulting in swelling and endothelial proliferation. The clinical manifestations of Fabry disease include severe pain in the limbs, skin lesions, eye opacities and deterioration of kidney and heart function. Elfabrio is a recombinant human GLA intended as enzyme-replacement therapy. For more information please consult the product for Elfabrio on the EMA website.
Hyftor (sirolimus): is indicated for the treatment of facial angiofibroma associated with tuberous sclerosis complex (TSC) in adults and paediatric patients aged 6 years and older. TSC is a rare autosomal dominant disease caused by loss-of-function mutations in the genes TSC1 or TSC2, encoding the proteins hamartin and tuberin, respectively. The disease is characterised by the presence of non-cancerous tumours, hamartomas, which appear in many vital organs including the brain, kidneys, heart and skin. This unregulated cell proliferation results from the hyperactivation of mammalian target of rapamycin (mTOR), normally suppressed by hamartin and tuberin. Angiofibromas are one type of skin manifestation of TSC and it is present in a great majority of patients.
Hyftor is an mTOR inhibitor and contains the same active substance as Rapamune, which has been authorised in the EU since 13 March 2001. Rapamune is authorised in the EU for prophylaxis of kidney transplant rejection and for the treatment of sporadic lymphangioleiomyomatosis. Although both contain the same active substance (sirolimus or rapamycin), Hyftor is available as a gel intended for local administration while Rapamune is available as an oral solution. For more information please consult the product for Hyftor on the EMA website.
Opzelura (ruxolitinib): is indicated for the treatment of non-segmental vitiligo with facial involvement in adults and adolescents from 12 years of age. Non-segmental, or generalised, vitiligo is an autoimmune disorder that manifests as acquired and progressive depigmented patches of the skin, mucosa and hair, caused by a selective loss of melanocytes. Although its aetiology is unknown, it is likely that stress, genetic, metabolic and environmental factors play a role in the onset of vitiligo. Furthermore, an interferon-gamma-mediated immune response via the activation Janus kinase/signal transducers and activators of transcription (JAK/STAT) signalling pathway has been linked to the pathogenesis of vitiligo.
Opzelura is a small molecule JAK inhibitor intended for topical administration and it is the first authorised treatment for this disorder. Ruxolitinib is also the active substance in the medicinal product Jakavi, authorised in the EU since August 2012 and intended for the treatment of myelofibrosis, polycythaemia vera and graft-versus-host disease. For more information please consult the product for Opzelura on the EMA website.
Tibsovo (ivosidenib): in combination with azacitidine is indicated for the treatment of adult patients with newly diagnosed acute myeloid leukaemia (AML) with an isocitrate dehydrogenase-1 (IDH1) R132 mutation who are not eligible to receive standard induction chemotherapy.
Furthermore, Tibsovo (ivosidenib) received a positive opinion for a second indication this month for the treatment, as monotherapy, of adult patients with locally advanced or metastatic cholangiocarcinoma (CCA) with an IDH1 R132 mutation who were previously treated by at least one prior line of systemic therapy.
AML is a cancer of the white blood cells characterised by the overproduction of immature myeloid cells and mutations in IDH can be found in up to 30% of AML patients.
CCA is a cancer of the bile duct with high genomic diversity. Recent next-generation sequence analyses have shown that many mutations typically found in other cancer types are also present in CCA, including mutations in IDH. Indeed, mutations in IDH have been found in around 15 to 20 % of intrahepatic CCA.
IDH1 is an enzyme of the tricarboxylic acid cycle responsible for the oxidative decarboxylation of isocitrate to α-ketoglutarate. Mutations in IDH lead to the accumulation of 2-hydroxyglutarate (2-HG), which affects numerous α-ketoglutarate-dependent processes such as histone and DNA methylation, thereby promoting malignant transformation. Tibsovo is first-in-class small molecule inhibitor of IDH1, exerting its effect by decreasing the levels of 2-HG. For more information please consult the product for Tibsovo on the EMA website.
Vafseo (vadadustat): is indicated for the treatment of symptomatic anaemia associated with chronic kidney disease (CKD) in adults on chronic maintenance dialysis. Several factors can contribute to the development of anaemia in patients with CKD, including insufficient production of erythropoietin, impaired iron absorption, shorter lifespan of red blood cells or blood loss associated with haemodialysis. Vafseo inhibits the hypoxia-inducible factor (HIF) prolyl hydroxylase, thereby stabilizing HIFs, which induce the expression of erythropoietin. For more information please consult the product for Vafseo on the EMA website.
Recommendations on extensions of therapeutic indication:
Esbriet (pirfenidone): extension of indication to the treatment of idiopathic pulmonary fibrosis (IPF) in adults. Esbriet was previously only authorised for the treatment of mild to moderate IPF. For more information please consult the product for Esbriet on the EMA website. For more information please consult the product for Esbriet on the EMA website.
Libtayo (cemiplimab): extension of indication to include, in combination with platinum‐based chemotherapy, the first-line treatment of adult patients with non-small cell lung cancer (NSCLC) expressing PD-L1 (in ≥ 1% of tumour cells), with no EGFR, ALK or ROS1 aberrations, who have locally advanced NSCLC who are not candidates for definitive chemoradiation, or metastatic NSCLC.
Libtayo as monotherapy was already authorised for the first-line treatment of adult patients with NSCLC expressing PD-L1 (in ≥ 50% tumour cells), with no EGFR, ALK or ROS1 aberrations, who have locally advanced NSCLC and who are not candidates for definitive chemoradiation, or metastatic NSCLC.
Furthermore, Libtayo was already authorised for the treatment of cutaneous squamous cell carcinoma, basal cell carcinoma and cervical cancer. For more information please consult the product for Libtayo on the EMA website.
Rinvoq (upadacitinib): extension of indication to the treatment of adult patients with moderately to severely active Crohn’s disease who have had an inadequate response, lost response or were intolerant to either conventional therapy or a biologic agent. Rinvoq was already authorised for the treatment of rheumatoid and psoriatic arthritis, axial spondyloarthritis, atopic dermatitis and ulcerative colitis. For more information please consult the product for Rinvoq on the EMA website.
TachoSil (human fibrinogen / human thrombin): extension of indication to the supportive treatment of children from 1 month of age in surgery for improvement of haemostasis, to promote tissue sealing and for suture support in vascular surgery where standard techniques are insufficient. TachoSil was already authorised in adults in this indication and for supportive sealing of the dura mater to prevent postoperative cerebrospinal leakage following neurological surgery. For more information please consult the product for TachoSil 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:
Hemgenix (etranacogene dezaparvovec): is indicated for the treatment of severe and moderately severe Haemophilia B (congenital Factor IX deficiency) in adult patients without a history of Factor IX inhibitors. EPAR Hemgenix.
Spevigo (spesolimab): is indicated for the treatment of flares in adult patients with generalised pustular psoriasis as monotherapy. EPAR Spevigo.
Recently started procedures:
- Cabotegravir - Pre-exposure prophylaxis of HIV-1 infection.
- Epcoritamab - Orphan - Treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma.
- Epinephrine - Treatment of allergic reactions (anaphylaxis) and idiopathic or exercise induced anaphylaxis.
- Lebrikizumab - Treatment of moderate-to-severe atopic dermatitis in adults and adolescents.
- Leniolisib - Orphan - Treatment of activated phosphoinositide 3-kinase delta syndrome.
- Vamorolone - Orphan - Treatment of Duchenne muscular dystrophy.Other topics of interest.
Other topics of interest
Update on the following authorised medicines for the prevention of COVID-19:
The CHMP has recommended authorising the use of COVID-19 Vaccine Valneva (inactivated, adjuvanted) as a booster dose for adults 18 to 50 years of age.