In the month of September 2021, medicinal products for the following indications have received a positive opinion:

• Severe malaria
• Waldenström’s macroglobulinaemia
• Rearranged during transfection (RET) fusion-positive advanced non-small cell lung cancer
• Advanced gastrointestinal stromal tumour
• Relapsing remitting multiple sclerosis

New medicines recommended for approval

Artesunate Amivas (artesunate) is indicated for the initial treatment of severe malaria in adults and children. Malaria is a mosquito-borne disease, caused by the infection of red blood cells with parasites belonging to the genus Plasmodium. Symptoms typically include headaches, tiredness, vomiting and fever and the disease is potentially fatal. Although the mechanism of action of artesunate is not fully understood, it is hypothesised that it reduces parasite growth through the inhibition of cell processes as a consequence of increased oxidative stress. It is active against asexual blood stages of Plasmodium species.

Brukinsa (zanubrutinib) as monotherapy is indicated for the treatment of adult patients with Waldenström’s macroglobulinaemia (WM) who have received at least one prior therapy, or in first line treatment for patients unsuitable for chemo-immunotherapy. WM is a type of cancer affecting white blood cells. These produce immunoglobulin M, which is found circulating at high levels. The disease presents systemic symptoms as a result of bone marrow infiltration. Brukinsa inhibits the tyrosine-protein kinase BTK, which plays a critical role in B cell development.

Gavreto (pralsetinib) received a positive opinion for a conditional marketing authorisation, for the treatment, as monotherapy, of adult patients with rearranged during transfection (RET) fusion-positive advanced non-small cell lung cancer (NSCLC) not previously treated with a RET inhibitor. RET is a proto-oncogene which encodes a tyrosine kinase receptor. Gain-of-function mutations in RET are associated with various types of cancer and oncogenic RET fusions are found in 1 to 2% of NSCLC patients. Gavreto is a tyrosine kinase inhibitor that targets oncogenic RET protein.

Qinlock (ripretinib) is indicated for the treatment of adult patients with advanced gastrointestinal stromal tumour (GIST) who have received prior treatment with three or more kinase inhibitors, including imatinib. GIST tumours arise in the smooth muscle interstitial cells of Cajal and the majority present a gain-of-function mutation of the proto-oncogenes KIT or PDGFRA (platelet-derived growth factor receptor A gene). Qinlock is a tyrosine kinase inhibitor that binds and inhibits KIT and PDGFRA proteins by locking them into their inactive state.

Vumerity (diroximel fumarate) is indicated for the treatment of adult patients with relapsing remitting multiple sclerosis. Multiple sclerosis is a chronic neurodegenerative autoimmune disease of the central nervous system, which leads to irreversible decrease in physical and cognitive function. Although the mechanism of action of Vumerity is not fully understood, non-clinical studies point to a possible activation of the nuclear factor erythroid 2-related factor 2 (NRF2). NRF2 may be involved in the regulation of the expression of proteins that protect against inflammation-induced oxidative stress.

Recommendations on extensions of therapeutic indication

Firmagon (degarelix): extension of indication to include the treatment of high-risk localized and locally advanced hormone-dependent prostate cancer in combination with radiotherapy and as neo-adjuvant treatment prior to radiotherapy in patients with high-risk localised or locally advanced hormone-dependent prostate cancer.

Jyseleca (filgotinib): extension of indication to include the treatment of adult patients with moderately to severely active ulcerative colitis who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a biologic agent. Jyseleca had previously been authorised for the treatment of rheumatoid arthritis.

Keytruda (pembrolizumab): extension of indication to include, in combination with chemotherapy, the treatment of locally recurrent unresectable or metastatic triple negative breast cancer in adults whose tumours express PD-L1 with a combined positive score (CPS) ≥ 10 and who have not received prior chemotherapy for metastatic disease. Keytruda had previously been 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 and oesophageal carcinoma.

Noxafil (posaconazole): extension of indication to the treatment of invasive aspergillosis. Noxafil had previously been authorised for the treatment and prophylaxis of other fungal infections.

Nucala (mepolizumab): extension of indication to include Nucala as an add-on the treatment of:

• Patients aged 6 years and older with relapsing-remitting or refractory eosinophilic granulomatosis with polyangiitis;
• Adult patients with inadequately controlled hypereosinophilic syndrome without an identifiable non-haematologic secondary cause;
• Adult patients with severe chronic rhinosinusitis with nasal polyps for whom therapy with systemic corticosteroids and/or surgery do not provide adequate disease control (add-on therapy with intranasal corticosteroids).

Nucala had previously been authorised for the treatment of eosinophilic asthma.

Opdivo (nivolumab): extension of indication in combination with fluoropyrimidine- and platinum-based combination chemotherapy, for the first‑line treatment of adult patients with HER2‑negative advanced or metastatic gastric, gastro‑oesophageal junction or oesophageal adenocarcinoma whose tumours express PD-L1 with a CPS ≥ 5. Opdivo had previously been authorised for the treatment of melanoma, non-small cell lung cancer, malignant pleural mesothelioma, renal cell carcinoma, classical Hodgkin lymphoma, squamous cell cancer of the head and neck, urothelial carcinoma, mismatch repair deficient or microsatellite instability-high colorectal cancer and oesophageal squamous cell carcinoma.

Zepatier (elbasvir / grazoprevir): extension of indication to include the treatment of chronic hepatitis C in paediatric patients 12 years of age and older who weigh at least 30 kg.

Newly published European Public Assessment Reports (EPAR)

The European Public Assessment Report (EPAR) is the main document where the European Medicines Agency (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:

Abecma (idecabtagene vicleucel) for the treatment of multiple myeloma. See EPAR Abecma.

Bimzelx (bimekizumab) for the treatment of plaque psoriasis. See EPAR Bimzelx.

Bylvay (odevixibat) for the treatment of progressive familial intrahepatic cholestasis. See EPAR Bylvay.

Byooviz (ranibizumab) for the treatment of ‘wet’ form of age-related macular degeneration, macular oedema, proliferative diabetic retinopathy and other sight problems associated with choroidal neovascularisation. See EPAR Byooviz.

Evrenzo (roxadustat) for the treatment of symptoms of anaemia caused by chronic kidney failure. See EPAR Evrenzo.

Imcivree (setmelanotide) for the treatment of obesity and to help control hunger caused by pro-opiomelanocortin deficiency or leptin receptor deficiency. See EPAR Imcivree.

Klisyri (tirbanibulin) for the treatment of mild actinic keratosis on the face and scalp. See EPAR Klisyri.

Minjuvi (tafasitamab) for the treatment of diffuse large B-cell lymphoma. See EPAR Minjuvi.

Ryeqo (relugolix / estradiol / norethisterone acetate) for the treatment of moderate to severe symptoms of uterine fibroids. See EPAR Ryeqo.

Skysona (elivaldogene autotemcel) for the treatment of early cerebral adrenoleukodystrophy. See EPAR Skysona.

Verquvo (vericiguat) for the treatment of long-term heart failure with reduced ejection fraction. See EPAR Verquvo.

Voxzogo (vosoritide) for the treatment of achondroplasia. See EPAR Voxzogo.

Recently started procedures

Every month, new marketing authorization applications are submitted to EMA under the centralized authorization procedure. The CHMP carries out a scientific assessment of the applications and gives a recommendation. The CHMP has started the assessment of the following submitted applications:

Initial marketing authorization applications:

• Copanlisib - Treatment of adult patients with relapsed marginal zone lymphoma.
• Budesonide, micronised - Treatment of primary immunoglobulin A nephropathy.
• Maribavir - Treatment of cytomegalovirus infection.
• Tezepelumab - Add-on maintenance treatment in adults and adolescents 12 years and older with severe asthma.
• Faricimab - Treatment of neovascular (wet) age-related macular degeneration and visual impairment due to diabetic macular oedema.

Other topics of interest

CHMP concludes Article 5(3) review on Vaxzevria

The article 5(3) of the European Regulation 726/2004 states that,

“At the request of the Executive Director of the Agency or the Commission representative, the Committee for Medicinal Products for Human Use shall also draw up an opinion on any scientific matter concerning the evaluation of medicinal products for human use. The Committee shall take due account of any requests by Member States for an opinion. The Committee shall also formulate an opinion whenever there is disagreement in the evaluation of medicinal products through the mutual recognition procedure. The opinion of the Committee shall be made publicly accessible”.

A scientific opinion was requested by the European Commission following the initial reports of thrombosis with thrombocytopenia syndrome (TTS) associated with this vaccine. The CHMP has concluded the analysis of data on the risk of TTS and on the use of a second dose of Vaxzevria:

• The evidence did not allow identifying particular risk factors that make TTS more likely.
• EMA’s recommendation remains to continue giving a second dose of Vaxzevria between 4 and 12 weeks after the first, in line with the product information.
• There is no evidence that delaying the second dose has any influence on the risk of TTS.
• No definitive recommendations on the use of a different vaccine for the second dose can be made at present.

For more information see the final assessment report of the Article 5(3) procedure on Vaxzevria.

Re-election of Harald Enzmann as CHMP chair

The CHMP re-elected Harald Enzmann as its chair for a second three-year term, starting in September 2021.

Information from EMA

Agenda, Minutes und Highlights of the CHMP