CHMP Meeting Highlights May 2022
This month, medicinal products for the following indications have received a positive opinion:
- Aromatic L‑amino acid decarboxylase deficiency
- Hutchinson-Gilford progeria syndrome
- Niemann-Pick disease (Acid Sphingomyelinase Deficiency)
- Primary immunoglobulin A nephropathy
- Processing-deficient progeroid laminopathy
New medicines recommended for approval:
Kinpeygo (budesonide): received a positive opinion for a conditional marketing authorisation (CMA) for the treatment of primary immunoglobulin A (IgA) nephropathy (IgAN) in adults at risk of rapid disease progression with a urine protein-to-creatinine ratio ≥1.5 g/gram. IgAN, also known as Berger’s disease, is a progressive autoimmune glomerulonephritis characterised by galactose-deficient IgA1 (GdIgA1) deposits within the glomeruli of the kidney. This accumulation triggers inflammatory events, ultimately causing irreversible scarring of the glomeruli (glomerulosclerosis) and loss of filtration capacity. The primary form of the disease is characterised by the lack of relevant associated co-morbidities. Although the aetiology is unknown, it has been shown that the mucosal immune system (particularly of the gastrointestinal tract) is involved in the development of the disease.
Kinpeygo is an oral modified release capsule formulation of budesonide, a drug of the corticosteroid type. With its two-step release mechanism, the capsule reaches the ileum intact; there, it disintegrates, releasing budesonide beads that ensure a prolonged release. Due to its high hepatic clearance, its systemic exposure is limited, thereby reducing the known risks of systemic glucocorticoids. Within the ilium, budesonide inhibits the proliferation and differentiation of mucosal B-cells into GdIgA1-producing plasma cells. Kinpeygo is a hybrid medicine of Entocort (budesonide), which has been authorised in the EU since 1992. Although they have the same active substance, they have different formulations and indication. For more information please consult the product for Kinpeygo on the EMA website.
Upstaza (eladocagene exuparvovec): received a positive opinion for an authorisation under exceptional circumstances based on an assessment by EMA’s Committee for Advanced Therapies (CAT) 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 (AADCD) with a severe phenotype. AADC deficiency is an ultra-rare autosomal recessive disease caused by mutations in the gene encoding the enzyme AADC, which is involved in the synthesis and regulation of several neurotransmitters, such as dopamine, epinephrine and norepinephrine. Although the clinical presentation of AADC deficiency is heterogeneous, common symptoms include muscular hypotonia, movement disorders and developmental delay.
Upstaza is the first medicine to receive a positive opinion for the treatment of AADC deficiency. It consists of an adeno-associated virus 2 (AAV2) containing the human DDC gene, which encodes the enzyme AADC. Upstaza is intended for a single treatment and is infused directly into the brain (putamen), where the AADC enzyme is subsequently expressed. The vector does not integrate in the host genome and has shown long-term expression in vivo. Upstaza is considered an advanced therapy medicinal product (ATMP). EMA news announcement on Upstaza. For more information please consult the product for Upstaza on the EMA website.
Xenpozyme (olipudase alfa): is indicated as an enzyme replacement therapy for the treatment of non-Central Nervous System (CNS) manifestations of Acid Sphingomyelinase Deficiency (ASMD) in paediatric and adult patients with type A/B or type B. ASMD, previously known as Niemann-Pick’s disease, is a rare autosomal recessive lysosomal storage disorder caused by mutations in the SMPD1 gene, which encodes the acid sphingomyelinase (ASM) enzyme. The lysosomal ASM catalyses the breakdown of sphingomyelin and its deficiency causes the progressive accumulation of sphingomyelin within the lysosomes. The clinical presentation is heterogeneous but often includes hepatosplenomegaly, interstitial lung disease and dyslipidaemia. Type A of the disease is characterised by an early onset and severe progressive neurodegeneration, while type B is predominantly associated with chronic progressive visceral symptoms. Type A/B, or intermediate ASMD, shows a similar progression to type B albeit with neurological involvement.
Xenpozyme is a recombinant ASM enzyme intended as replacement therapy. EMA news announcement on Xenpozyme. For more information please consult the product for Xenpozyme on the EMA website.
Zokinvy (lonafarnib): received a positive opinion for an authorisation under exceptional circumstances 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. It is the first treatment authorised for this indication.
Hutchinson-Gilford progeria syndrome (HGPS) and progeroid laminopathies (PLs) are ultra-rare disorders classified as progeroid syndromes, a group of genetic disorders characterised by premature ageing. HGPS, or classic progeria, is caused by a mutation that activates a cryptic splice site, which results in an aberrant farnesylated version of prelamin A that lacks the ZMPSTE24 cleavage site. This aberrant protein is called progerin and it cannot be further post-translationally processed into lamin A, leading to accumulation within the cell nucleus. Lamin A is pivotal to promoting genetic stability.
PLs are caused by mutations in the LMNA gene, which encodes prelamin A, or proteins that participate in the post-translational modifications of prelamin A. In the case of processing-deficient laminopathies, these mutations result in accumulation of progerin-like proteins.
Apart from premature ageing, these conditions are associated with progressive cardiovascular disease, failure to thrive and full-body alopecia, amongst other.
Zokinvy is an oral inhibitor of farnesyltransferase, which prevents farnesylation of prelamin A and the subsequent accumulation of progerin and progerin-like proteins. EMA news announcement on Zokinvy.
As specific obligation, a prospective observational cohort study based on a registry will further characterise the safety, effectiveness and health-related quality of life of Zokinvy in patients with Hutchinson-Gilford progeria syndrome and processing deficient progeroid laminopathies. For more information please consult the product for Zokinvy on the EMA website.
Recommendations on extensions of therapeutic indication:
Cosentyx (secukinumab): extension of indication, alone or in combination with methotrexate (MTX), to the treatment of active enthesitis-related arthritis and juvenile psoriatic arthritis in patients 6 years and older whose disease has responded inadequately to, or who cannot tolerate, conventional therapy.
Cosentyx was already authorised for the treatment of adult and paediatric plaque psoriasis, psoriatic arthritis, axial and non-radiographic axial spondyloarthritis. For more information please consult the product for Cosentyx on the EMA website.
Keytruda (pembrolizumab): extension of indication, as monotherapy, to the treatment of adolescents aged 12 years and older with advanced (unresectable or metastatic) melanoma. Furthermore, extension of indication for Keytruda as monotherapy to the treatment of adults and adolescents ages 12 years and older with Stage IIB and IIC melanoma, who have undergone complete resection.
Keytruda was already authorised for the treatment of melanoma, non-small cell lung cancer, classical Hodgkin lymphoma, urothelial cancer, head and neck squamous cell carcinoma, renal cell carcinoma, colorectal cancer, oesophageal carcinoma, triple-negative breast cancer, endometrial carcinoma, cervical cancer, gastric cancer, small intestine cancer and biliary cancer. For more information please consult the product for Keytruda on the EMA website.
Nexpovio (selinexor): extension of indication for Nexpovio in combination with bortezomib and dexamethasone to the treatment of adult patients with multiple myeloma who have received at least one prior therapy. Nexpovio has been previously authorized for the treatment of multiple myeloma in adult patients who have received at least four prior therapies. For more information please consult the product for Nexpovio on the EMA website.
Olumiant (baricitinib): extension of indication to the treatment of severe alopecia areata in adult patients. Olumiant was already authorised for the treatment of rheumatoid arthritis and atopic dermatitis. For more information please consult the product for Olumiant on the EMA website.
Rinvoq (upadacitinib): extension of indication to the treatment of adult patients with moderately to severely active ulcerative colitis 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, ankylosing spondylitis and atopic dermatitis. For more information please consult the product for Rinvoq on the EMA website.
Xeljanz (tofacitinib): extension of indication to the treatment of adult patients with active ankylosing spondylitis who have responded inadequately to conventional therapy. Xeljanz was already authorised for the treatment of rheumatoid and psoriatic arthritis. For more information please consult the product for Xeljanz 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:
Evusheld (tixagevimab / cilgavimab): is indicated for the pre-exposure prophylaxis of COVID-19 in adults and adolescents aged 12 years and older weighing at least 40 kg. EPAR Evusheld.
Kapruvia (difelikefalin): is indicated for the treatment of moderate-to-severe pruritus associated with chronic kidney disease in adult patients on haemodialysis. EPAR Kapruvia.
Lumykras (sotorasib): as monotherapy is indicated 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. EPAR Lumykras.
Orgovyx (relugolix): is indicated for the treatment of adult patients with advanced hormone-sensitive prostate cancer. EPAR Orgovyx.
Padcev (enfortumab vedotin): as monotherapy is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received a platinum-containing chemotherapy and a programmed death receptor-1 or programmed death-ligand 1 inhibitor. EPAR Padcev.
Prehevbri (hepatitis B surface antigen): is indicated for active immunisation against infection caused by all known subtypes of the hepatitis B virus in adults. EPAR PreHevbri.
Quviviq (daridorexant): is indicated for the treatment of adult patients with insomnia characterised by symptoms present for at least 3 months and considerable impact on daytime functioning. EPAR Quviviq.
Tepmetko (tepotinib): as monotherapy is indicated for the treatment of adult patients with advanced non-small cell lung cancer (NSCLC) harbouring alterations leading to mesenchymal-epithelial transition factor gene exon 14 (METex14) skipping, who require systemic therapy following prior treatment with immunotherapy and/or platinum-based chemotherapy. EPAR Tepmetko.
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. EPAR Uplizna.
Vydura (rimegepant): is indicated for the acute treatment of migraine with or without aura in adults and for the preventive treatment of episodic migraine in adults who have at least 4 migraine attacks per month. EPAR Vydura.
Recently started procedures:
- Daprodustat - Treatment of anaemia associated with chronic kidney disease in adults.
- Gadopiclenol - Diagnostic, contrast-enhanced magnetic resonance imaging (MRI) to improve detection, visualization and assist in characterization of lesions in the central nervous system and in other body regions (including breast, liver and prostate).
- Nirsevimab - Immunise infants from birth entering their first Respiratory Syncytial Virus (RSV) season for the prevention of RSV lower respiratory tract disease.
- Pegunigalsidase alfa - Orphan - Treatment of Fabry disease.
- Sodium phenylbutyrate / ursodoxicoltaurine - Orphan - Treatment of amyotrophic lateral sclerosis.
- Teclistamab - Orphan - Treatment of relapsed or refractory multiple myeloma.
Other topics of interest:
Referral procedure under Article 29(4) for Daruph/Anafezyn (dasatinib anhydrous):
The CHMP completed a review of Daruph/Anafezyn, initially submitted as DC under Article 10(3) of Directive 2001/83/EC (hybrid), following a disagreement among EU Member States regarding its authorisation. The CHMP recommends granting a marketing authorisation in the Member States of the EU where the company applied for it (France, Germany, Hungary, Ireland, Italy, Poland, Portugal, Romania, Sweden and Slovakia). Daruph/Anafezyn is a cancer medicine to be used in adults and children to treat chronic myeloid leukaemia and acute lymphoblastic leukaemia. Unlike currently available dasatinib products, there is no warning against the use of Daruph/Anafezyn in combination with proton pump inhibitors. For more information about this referral, see the public health communication on Daruph/Anafezyn.
The CHMP recommended including the use of Vaxzevria as a booster dose for adults who have completed the primary vaccination course with this vaccine or an approved mRNA COVID-19 vaccine.