CHMP Meeting Highlights September 2023

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

• Acute myeloid leukaemia
• Atopic dermatitis
• Generalised myasthenia gravis
• Heart failure
• Hypoparathyroidism
• Low- and high-grade glioma

New medicines recommended for approval:

Aqumeldi (enalapril maleate): is indicated for the treatment of heart failure in children from birth to less than 18 years. Heart failure is an impairment of the blood pumping function of the heart and reduced efficiency of the heart muscle. In children it is most commonly caused by congenital heart defects. The renin-angiotensin system (RAS) is the endocrine system involved in the regulation of blood pressure and vascular resistance, amongst other. The angiotensin-converting enzyme (ACE), a part of RAS, converts angiotensin I into angiotensin II, an active vasoconstrictor, thereby increasing blood pressure. Aqumeldi is an ACE inhibitor, a class of drugs also indicated for the treatment of blood pressure. Aqumeldi is a hybrid medicine of Renitec, which has been authorised in the EU since 1985. Although both contain the same active substance, Aqumeldi is available at lower strength and in a formulation more appropriate for children. The application for Aqumeldi was submitted as a paediatric-use marketing authorisation (PUMA). For more information please consult the product for Aqumeldi on the EMA website.

Ebglyss (lebrikizumab): is indicated for the treatment of moderate-to-severe atopic dermatitis (AD) in adults and adolescents 12 years and older with a body weight of at least 40 kg who are candidates for systemic therapy. AD is a chronic and complex disease, characterised by dry and pruritic skin. The main contributors seem to be an altered permeability of the skin due to perturbations in the epidermal barrier and an inappropriate immune response, which results in skin inflammation and contributes to the epidermal barrier disruption. Interleukin 13 (IL-13) is believed to be key in the pathophysiology of AD. Ebglyss is a monoclonal antibody that binds and inhibits IL-13, thereby disrupting the cytokine signalling cascade involved in AD. For more information please consult the product for Ebglyss on the EMA website.

Finlee (dabrafenib): has received a positive opinion for the following indications:

Low-grade glioma

Finlee in combination with trametinib is indicated for the treatment of paediatric patients aged 1 year and older with low-grade glioma (LGG) with a BRAF V600E mutation who require systemic therapy.

High-grade glioma

Finlee in combination with trametinib is indicated for the treatment of paediatric patients aged 1 year and older with high-grade glioma (HGG) with a BRAF V600E mutation who have received at least one prior radiation and/or chemotherapy treatment.

Gliomas are a group of primary tumours of the central nervous system with glial origin. LGG are rare and HGG even rarer tumours in the paediatric population. The BRAF V600E mutation is present in around 17% of paediatric LGG cases and in 6% of paediatric and young adult cases of HGG. Finlee is a small molecule inhibitor of the V600-mutant BRAF kinase and trametinib is a small molecule inhibitor of the mitogen-activated protein kinase (MEK). Finlee has been developed with a dispersible tablet formulation, suitable for the paediatric population. An application for a pharmaceutical form suitable for the paediatric population, powder for oral solution, of trametinib is currently being assessed by CHMP for in indication in combination with Finlee. For more information please consult the product for Finlee on the EMA website.

Vanflyta (quizartinib): is indicated in combination with standard cytarabine and anthracycline induction and standard cytarabine consolidation chemotherapy, followed by Vanflyta single-agent maintenance therapy for adult patients with newly diagnosed acute myeloid leukaemia (AML) that is FLT3-ITD positive.

AML is a cancer of the white blood cells characterised by the overproduction of immature myeloid cells. Mutations in FLT3 are one of the most common in newly diagnosed AML, and the internal tandem duplication (ITD) in FLT3 is associated with aggressive malignancies and unfavourable prognosis, due to a high rate of relapse. Vanflyta is a small molecule inhibitor of FLT3, which binds at the ATP-binding pocket, thereby preventing downstream signalling and FLT3-ITD-dependent proliferation. For more information please consult the product for Vanflyta on the EMA website.

Yorvipath (palopegteriparatide): is a parathyroid hormone (PTH) replacement therapy indicated for the treatment of adults with chronic hypoparathyroidism (HPT). HPT is a rare disease characterised by a reduced function of the parathyroid glands, which results in a lower production of PTH. Although HPT can be a result of genetic and autoimmune factors, the majority of the cases arise after complications from neck surgery. The main symptoms of HPT are a consequence of low calcium levels. Yorvipath is a prodrug consisting of the first 34 aminoacids of the endogenous PTH, conjugated to an inert methoxypolyethylene glycol (mPEG) carrier via a linker, which is cleaved after administration releasing the active moiety. For more information please consult the product for Yorvipath on the EMA website.

Zilbrysq (zilucoplan): is indicated as an add-on to standard therapy for the treatment of generalised myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) antibody positive. MG is a rare autoimmune disorder 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 (NMJ), leading to failure of neuromuscular transmission. Activation of the complement system has been shown in the NMJ. Zilbrysq is a macrocyclic peptide that inhibits the protein complement component 5 (C5), a component of the terminal complement system. For more information please consult the product for Zilbrysq on the EMA website.

Recommendations on extensions of therapeutic indication:

Adcetris (brentuximab vedotin): extension of indication to the treatment of adult patients with previously untreated CD30+ Stage III Hodgkin lymphoma in combination with doxorubicin, vinblastine and dacarbazine. Adcetris was already authorised for different stages of Hodgkin lymphoma, and various lines of therapy; for systemic anaplastic large cell lymphoma and cutaneous T-cell lymphoma. For more information please consult the product for Adcetris on the EMA website.

Enhertu (trastuzumab deruxtecan): extension of indication to include, as monotherapy, treatment of adult patients with advanced non-small cell lung cancer whose tumours have an activating HER2 (ERBB2) mutation and who require systemic therapy following platinum-based chemotherapy with or without immunotherapy. Enhertu was already authorised for breast cancer and gastric cancer. For more information please consult the product for Enhertu on the EMA website.

Kaftrio (ivacaftor/tezacaftor/elexacaftor) granules: extension of indication, in a combination regimen with ivacaftor, to include treatment of cystic fibrosis in patients aged 2 to less than 6 years who have at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Kaftrio was already authorised, as capsules, in adults and children from 6 years of age. For more information please consult the product for Kaftrio on the EMA website.

Kalydeco (ivacaftor) granules: extension of indication, in a combination regimen with ivacaftor/tezacaftor/elexacaftor, to include treatment of cystic fibrosis in patients aged 2 to less than 6 years who have at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Kalydeco was already authorised, as tablets, in adults and children from 6 years of age with at least one F508del mutation in the CFTR gene, and as monotherapy in children from 4 months of age with different mutations. For more information please consult the product for Kalydeco on the EMA website.

Keytruda (pembrolizumab): extension of indication to include, as monotherapy, the adjuvant treatment of adults with non-small cell lung carcinoma who are at high risk of recurrence following complete resection and platinum-based chemotherapy. Keytruda was already authorised for the treatment of melanoma, non-small cell lung carcinoma, classical Hodgkin lymphoma, urothelial carcinoma, head and neck squamous cell carcinoma, renal cell carcinoma, colorectal cancer, oesophageal carcinoma, breast cancer, endometrial carcinoma, gastric or gastro-oesophageal junction (GEJ) adenocarcinoma, cervical cancer and several microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) cancers. For more information please consult the product for Keytruda on the EMA website.

Nordimet (methtotrexate): update of indication to the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy severe and severe psoriatic arthritis in adult patients. Nordimet was previously authorised only in severe recalcitrant disabling psoriasis, not adequately responsive to other forms of therapy such as phototherapy, psoralens and ultraviolet A (PUVA), and retinoids, and severe psoriatic arthritis in adult patients. Nordimet was already authorised for the treatment of active rheumatoid arthritis, juvenile idiopathic arthritis and Crohn's disease. For more information please consult the product for Nordimet on the EMA website.

Olumiant (baricitinib): extension of indication to the treatment of moderate to severe atopic dermatitis in paediatric patients 2 years and older who are candidates for systemic therapy. Olumiant was previously only authorised in adults in this indication. Furthermore, Olumiant was already authorised for the treatment of rheumatoid arthritis, alopecia areata and juvenile idiopathic arthritis. For more information please consult the product for Olumiant on the EMA website.

Pepaxti (melphalan flufenamide) extension of indication, in combination with dexamethasone, to the treatment of adult patients with multiple myeloma who have received at least two prior lines of therapies, whose disease is refractory to lenalidomide and the last line of therapy. Pepaxti was previously only authorised in patients who had received at least 3 lines of therapy and were refractory to at least one proteasome inhibitor, one immunomodulatory agent, and one anti-CD38 monoclonal antibody. For more information please consult the product for Pepaxti on the EMA website.

Ryeqo (relugolix / estradiol / norethisterone acetate): extension of indication to the symptomatic treatment of endometriosis in women with a history of previous medical or surgical treatment for their endometriosis. Ryeqo was previously authorised for the symptomatic treatment of uterine fibroids. For more information please consult the product for Ryeqo on the EMA website.

Takhzyro (lanadelumab):extension of indication to the routine prevention of recurrent attacks of hereditary angioedema in patients aged 2 years and older. Takhzyro was previously authorised in patients 12 years of age and older. For more information please consult the product for Takhzyro on the EMA website.

Voxzogo (vosoritide): extension of indication to the treatment of achondroplasia in patients 4 months of age and older whose epiphyses are not closed. Voxzogo was previously authorised in patients 2 years of age and older. For more information please consult the product for Voxzogo 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:

Abrysvo (Respiratory syncytial virus vaccines): is indicated for:

• Passive protection against lower respiratory tract disease caused by respiratory syncytial virus (RSV) in infants from birth through 6 months of age following maternal immunisation during pregnancy.
• Active immunisation of individuals 60 years of age and older for the prevention of lower respiratory tract disease caused by RSV. EPAR Abrysvo.

Aquipta (atogepant): is indicated for prophylaxis of migraine in adults who have at least 4 migraine days per month. EPAR Aquipta.

Camzyos (mavacamten): is indicated for the treatment of symptomatic (New York Heart Association, NYHA, class II-III) obstructive hypertrophic cardiomyopathy in adult patients. EPAR Camzyos.

Pylclari (piflufolastat [18F]): is indicated for the detection of prostate-specific membrane antigen (PSMA) positive lesions with positron emission tomography (PET) in adults with prostate cancer (PCa) in the following clinical settings:

• Primary staging of patients with high-risk PCa prior to initial curative therapy,
• To localize recurrence of PCa in patients with a suspected recurrence based on increasing serum prostate-specific antigen (PSA) levels after primary treatment with curative intent. EPAR Pylclari.

Ztalmy (ganaxolone): is indicated for the adjunctive treatment of epileptic seizures associated with cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder in patients 2 to 17 years of age. Ztalmy may be continued in patients 18 years of age and older. EPAR Ztalmy.

Recently started procedures:

• Apadamtase alfa - Orphan - Treatment of congenital thrombotic thrombocytopenic purpura due to ADAMTS13 deficiency.
• Capivasertib - Is indicated in combination with fulvestrant for the treatment of adult patients with hormone receptor positive, human epidermal growth factor receptor 2 (HER2) negative (defined as IHC 0 or 1+, or IHC 2+/ISH-) locally advanced or metastatic breast cancer following recurrence or progression on or after an endocrine based regimen.
• Efanesoctocog alfa - Orphan - Treatment and prophylaxis of bleeding in patients with haemophilia A.
• Fidanacogene elaparvovec - Orphan - Advanced therapy medicinal product - Indicated for the treatment of severe and moderately severe haemophilia B.
• Insulin icodec - Treatment of diabetes mellitus in adults.
• Iptacopan - Orphan - Treatment of paroxysmal nocturnal haemoglobinuria.
• Vibegron - Treatment of micturition frequency and/or urgency incontinence as may occur in adult patients with Over Active Bladder syndrome.

Further inquiry note

basg_anfragen@basg.gv.at