CHMP Meeting Highlights February 2022

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

• Immunisation against hepatitis B virus
• Insomnia
• Migraine
• Prostate cancer
• Pruritus associated with chronic kidney disease
• Urothelial cancer
• Uveal melanoma

New medicines recommended for approval:

Kapruvia (difelikefalin): is indicated for the treatment of moderate-to-severe pruritus associated with chronic kidney disease (CKD-aP) in adult patients on haemodialysis. Between 20 to 40% of patients undergoing haemodialysis suffer from moderate-to-severe pruritus. This chronic (and often generalised) itching is a severely distressing symptom that strongly reduces quality of life. Although the mechanisms underlying CKD-aP, or uremic pruritus, remain poorly understood, it is believed that the aetiology might be multifactorial, involving systemic inflammation and an altered endogenous opioid system (downregulation of the kappa opioid receptor (KOR) and upregulation of the mu opioid receptor). Kapruvia activates KORs, thereby exerting its antipruritic effects. For more information please consult the product page for Kapruvia on the EMA website.

Kimmtrak (tebentafusp): is indicated as monotherapy for the treatment of human leukocyte antigen (HLA) A*02:01 positive adult patients with unresectable or metastatic uveal melanoma (UM). UM is a rare type of malignant tumour of the eye, which arises from melanocytes present in the uvea. UMs respond poorly to therapies authorised for cutaneous melanoma, since these tumours are clinically, biologically and genetically different. Tebentafusp is a bispecific fusion protein. On the one side, tebentafusp has a T-cell receptor (TCR) targeting the antigen glycoprotein 100 (gp100) on the tumour cells, which is the first time that targeting gp100 is used for the treatment of cancer.  On the other side, tebentafusp has an anti-CD3 single-chain variable fragment that binds to T cells. Upon activation, these T cells trigger the cytokine-induced lysis of the tumour cells. Due to the specificity of its TCR domain, Kimmtrak is only effective in patients with the HLA A*02:01 allele. For more information please consult the product page for Kimmtrak on the EMA website.

Orgovyx (relugolix): is indicated for the treatment of adult patients with advanced hormone-sensitive prostate cancer. 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. In hormone-sensitive prostate cancer, the treatment objective is to reduce the levels of circulating testosterone by interfering with the hypothalamic–pituitary–gonadal axis. Relugolix is a non-peptide gonadotropin-releasing hormone (GnRH) receptor antagonist, which binds to the GnRH receptor, ultimately reducing the production of testosterone. As a first oral GnRH antagonist, Orgovyx is intended to be taken daily, thereby reducing the risks associated with the existing monthly-depot injection treatments, such as clinical flares, cardiovascular events or injection-site reactions.The active substance relugolix is already authorized in the product Ryeqo (relugolix/estradiol/norethisterone acetate) for the treatment of uterine fibroids. For more information please consult the product page for Orgovyx on the EMA website.

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.
The CHMP had adopted a positive opinion in December 2021 for Padcev (see the CHMP Highlights for December 2021). New safety information emerged during the decision-making process. Following a request from the European Commission and after assessing the new safety information, the CHMP re-adopted its positive opinion in February 2022. For more information please consult the product page for Padcev on the EMA website.

PreHevbri (Hepatitis B vaccine [recombinant, adsorbed]): is indicated for active immunisation against infection caused by all known subtypes of the hepatitis B virus (HBV) in adults. HBV causes hepatitis, an inflammation of the liver, which can become chronic and, ultimately, lead to cirrhosis and hepatocellular carcinoma. Despite available vaccines, hepatitis caused by HBV remains a global health problem. Adults who were not vaccinated during childhood remain at risk of becoming infected and up to 10% of adults fail to achieve seroprotective levels with the current vaccination schedule. PreHevbrio is a recombinant vaccine produced by expression of the HBV surface antigen in mammalian cells. The generated particles resemble the naturally occurring viral particles, conferring PreHevbrio with an increased immunogenicity as compared to existing yeast-derived vaccines. For more information please consult the product page for PreHevbri on the EMA website.

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. Insomnia is a sleep disorder in which the quality or the quantity of sleep are insufficient. Quviviq is a specific antagonist of the orexin neuropeptide receptors 1 and 2, or dual orexin receptor antagonist (DORA). Quviviq inhibits the activation of these receptors, thereby improving sleep latency and maintenance. Quviviq is the first DORA recommended by CHMP. For more information please consult the product page for Quviviq on the EMA website.

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. 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. Vydura is an anti-CGRPs small molecule which binds to CGRPs, thereby preventing the development of the cascade of events that result in a migraine attack. Vydura is the first drug that is effective in the acute and prophylactic treatment of migraine recommended by CHMP. For more information please consult the product page for Vydura on the EMA website.

Recommendations on extensions of therapeutic indication:

Beovu (brolucizumab): extension of indication to include the treatment of visual impairment due to diabetic macular oedema. Beovu had been previously authorised for the treatment of neovascular (wet) age related macular degeneration. For more information please consult the product for Beovu on the EMA website.

Delstrigo (doravirine / lamivudine / tenofovir disoproxil): extension of indication to include the treatment of adolescents aged 12 years and older weighing at least 35 kg who are infected with HIV-1 without past or present evidence of resistance to the NNRTI class, lamivudine, or tenofovir and who have experienced toxicities which preclude the use of other regimens that do not contain tenofovir disoproxil. For more information please consult the product for Delstrigo on the EMA website.

Opdivo (nivolumab): has received an authorisation for several extensions of indication:

• as monotherapy, for the adjuvant treatment of adults with muscle invasive urothelial carcinoma (MIUC) with tumour cell PD-L1 expression ≥ 1%, who are at high risk of recurrence after undergoing radical resection of MIUC
• in combination with fluoropyrimidine- and platinum-based combination chemotherapy, for the first-line treatment of adult patients with unresectable advanced, recurrent or metastatic oesophageal squamous cell carcinoma with tumour cell PD-L1 expression ≥ 1%
• in combination with ipilimumab, for the first-line treatment of adult patients with unresectable advanced, recurrent or metastatic oesophageal squamous cell carcinoma with tumour cell PD-L1 expression ≥ 1%

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, colorectal cancer and gastric, gastro-oesophageal junction or oesophageal adenocarcinoma. For more information please consult the product for Opdivo on the EMA website.

Pifeltro (doravirine): extension of indication to include the treatment of adolescents aged 12 years and older weighing at least 35 kg infected with HIV‑1. For more information please consult the product for Pifeltro on the EMA website.

Spikevax (COVID-19 mRNA vaccine [nucleoside-modified]): extension of indication to include the active immunisation to prevent COVID-19 caused by SARS-CoV-2 in children 6 to 11 years of age. For more information, see the EMA press release on Spikevax.

For more information, see:

• EMA press release on Spikevax
• Spikevax on the EMA website

Verzenios (abemaciclib): extension of indication, in combination with endocrine therapy, for the adjuvant treatment of adult patients with hormone receptor (HR)‑positive, human epidermal growth factor receptor 2 (HER2)‑negative, node‑positive early breast cancer at high risk of recurrence. Verzenios had already been authorised for the treatment of locally advanced or metastatic breast cancer. For more information please consult the product for Verzenios on the EMA website.

Yervoy (ipilimumab): extension of indication to include the first-line treatment of adult patients with unresectable advanced, recurrent or metastatic oesophageal squamous cell carcinoma with tumour cell PD-L1 expression ≥ 1%, in combination with nivolumab. Yervoy had previously been authorised for the treatment of melanoma, renal cell carcinoma, non-small cell lung cancer, malignant pleural mesothelioma and colorectal cancer. For more information please consult the product for Yervoy 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:

Lonapegsomatropin Ascendis Pharma (lonapegsomatropin): is indicated for the treatment of growth failure in children and adolescents with growth hormone deficiency. EPAR Lonapegsomatropin Ascendis Pharma.

Okedi (risperidone): is indicated for the treatment of schizophrenia in adults. EPAR Okedi.

Paxlovid (nirmatrelvir/ritonavir): is indicated for the treatment of COVID-19. EPAR Paxlovid.

Rybrevant (amivantamab): is indicated for treatment of adult patients with advanced non-small cell lung cancer. EPAR Rybrevant.

Saphnelo (anifrolumab): is indicated as an add-on therapy for the treatment of adult patients with systemic lupus erythematosus. EPAR Saphnelo.

Vyepti (eptinezumab): is indicated for the prophylaxis of migraine in adults. EPAR Vyepti.

Recently started procedures:

• Tabelecleucel - Orphan - ATMP (advanced therapy medicinal product) - Treatment of Epstein-Barr virus positive post-transplant lymphoproliferative disease.
• Abaloparatide - Treatment of osteoporosis.
• Spironolactone - Management of refractory oedema.
• Molnupiravir - Treatment of COVID-19.
• Fosdenopterin - Orphan - Treatment of molybdenum cofactor deficiency type A.
• Nvx-cov2373 - Prevention of COVID-19.
• Miglustat - Orphan - Treatment of adults aged 18 years and older with a confirmed diagnosis of Pompe disease.
• Cipaglucosidase alfa - Orphan - Treatment of adults aged 18 years and older with a confirmed diagnosis of Pompe disease.
• Infigratinib - Orphan - Treatment of cholangiocarcinoma.
• Vadadustat - Treatment of anaemia.
• Olipudase alfa - Orphan - Indicated as a disease-modifying enzyme replacement therapy for long-term treatment of non-Central Nervous System manifestations of Acid Sphingomyelinase Deficiency in paediatric and adult patients.
• Sotrovimab - Treatment of COVID-19.

Other topics of interest:

COVID-19:

The CHMP recommended that a booster dose of the COVID-19 vaccine Comirnaty (tozinameran) may be given, where appropriate, to adolescents from 12 years of age. For more information, see the news announcement on Comirnaty.
The CHMP also recommended including the use of Spikevax as a booster dose in people who have previously completed a primary vaccination with another mRNA vaccine or an adenoviral vector vaccine.

Previous CHMP Meeting Highlights can be accessed at: https://www.basg.gv.at/en/healthcare-professionals/chmp-highlights

Further inquiry note

basg_anfragen@basg.gv.at