CHMP Meeting Highlights July 2022
This month, medicinal products for the following indications have received a positive opinion:
- Diabetic macular oedema
- Hereditary transthyretin-mediated amyloidosis
- Lupus nephritis
- Molybdenum cofactor deficiency type A
- Multiple myeloma
- Neovascular (wet) age-related macular degeneration
- Type 2 diabetes
New medicines recommended for approval:
Amvuttra (vutrisiran): is indicated for the treatment of hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis) in adult patients with stage 1 or stage 2 polyneuropathy. hATTR amyloidosis is a rare and severe autosomal dominant disease, characterised by multisystem amyloid depositions. The most common clinical presentations include polyneuropathy and cardiomyopathy. hATTR is caused by mutations in the TTR gene (encoding the transport protein transthyretin), which cause protein misfolding, aggregation and subsequent deposition. Amvuttra is a small interfering RNA (siRNA) that targets and induces the degradation of the TTR messenger RNA (both wild-type and mutated), thereby reducing the amount of circulating TTR and slowing down its deposition. For more information please consult the product for Amvuttra on the EMA website.
Lupkynis (voclosporin): is indicated, in combination with mycophenolate mofetil, for the treatment of adult patients with active class III, IV or V (including mixed class III/V and IV/V) lupus nephritis (LN).
Systemic lupus erythematosus is a multifactorial chronic and multi-systemic autoimmune disease with LN, a type of glomerulonephritis, being its most common serious manifestation. LN is divided according to the pathology of the disease into 6 different classes (I-VI), which serve as criteria to guide treatment. Lupkynis exerts its immunosuppressant activity by inhibiting calcineurin. For more information please consult the product for Lupkynis on the EMA website.
Mounjaro (tirzepatide): is indicated for the treatment of adults with insufficiently controlled type 2 diabetes mellitus (T2DM) as an adjunct to diet and exercise
- as monotherapy when metformin is considered inappropriate due to intolerance or contraindications.
- in addition to other medicinal products for the treatment of diabetes.
T2DM is a metabolic disease characterised by high blood sugar and insulin resistance and it accounts for around 90% of diabetes cases. Although some people can have certain genetic predisposition, T2DM occurs primarily as a result of obesity and sedentary lifestyle. The prevalence of T2DM continues to increase globally along with obesity and overweight. Mounjaro is a first-in-class dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist. By activating the GIP and GLP-1 receptors, Mounjaro improves blood sugar control. Mounjaro is intended for weekly subcutaneous administration. For more information please consult the product for Mounjaro on the EMA website.
Nulibry (fosdenopterin): received a positive opinion for an authorisation under exceptional circumstances for the treatment of patients with molybdenum cofactor deficiency (MoCD) Type A. MoCD is an ultra-rare metabolic disorder, inherited in an autosomal recessive manner and caused by mutations in several genes. Patients with MoCD Type A present loss-of-function mutations in the MOCS1 gene, encoding molybdenum cofactor biosynthesis protein 1 (MOCS1), and account for the majority of MoCD patients. Without functional MOCS1, the intermediate cyclic pyranopterin monophosphate (cPMP) cannot be synthesized, interrupting the molybdenum cofactor (MoCo) metabolic pathway. This results in a lack of functional sulphite oxidase, which depends on MoCo, and an accumulation of sulphites.
The disease usually appears in neonates and manifests with intractable seizures, failure to thrive and other symptoms, which precede rapid neurodegeneration. Nulibry is a synthetic cPMP intended for substrate replacement therapy, restoring the MoCo metabolic pathway. For more information please consult the product for Nulibry on the EMA website.
Opdualag (relatlimab / nivolumab): is indicated for the first line treatment of advanced (unresectable or metastatic) melanoma in adults and adolescents 12 years of age and older with tumour cell PD-L1 expression < 1%.
Melanoma is a cancer that develops from melanocytes, which are pigment-producing cells. The most common subtype is cutaneous melanoma. Unless detected and surgically removed at an early stage, melanomas massively metastasise. Available pharmacological therapies have considerably improved the survival of patients with metastatic melanoma. However, there is still a considerable number of patients who either fail to respond to or relapse after treatment with available therapies.
Opdualag is a fixed-dose combination of the monoclonal antibodies relatlimab and nivolumab.
Relatlimab is a monoclonal antibody targeting the cell surface receptor LAG-3 (lymphocyte-activation gene 3). Upon binding, relatlimab blocks ligand binding thereby promoting anti-tumour immunity. Nivolumab is a checkpoint inhibitor targeting PD-1 (programmed cell death protein 1) on immune cells and has previously been approved for the therapy of various cancers under the tradename Opdivo®. Many cancer cells express a PD-1 ligand (PD-L1). Since activation of PD-1 downregulates the immune system, blocking of the interaction between PD-1 and PD-L1 enhances the T-cell responses against cancer cells. For more information please consult the product for Opdualag on the EMA website.
Tecvayli (teclistamab): received a positive opinion for a conditional marketing authorisation (CMA) for the treatment, as monotherapy, of adult patients with relapsed and refractory multiple myeloma (MM), who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody and have demonstrated disease progression on the last therapy. MM is a type of blood cancer characterized by the malignant proliferation of plasma cells that consistently express the B-cell maturation antigen (BCMA). BCMA is not expressed in normal non-haematopoietic cells.
Tecvayli is a bispecific antibody that targets CD3, present on the surface of T-cells, and BCMA. Tecvayli binds CD3, thereby eliciting recruitment of effector T-cells. Upon concurrent binding with BCMA, T-cell activation occurs, resulting in T-cell-mediated B-cell lysis. For more information please consult the product for Tecvayli on the EMA website.
Tezspire (Tezepelumab): is indicated as an add-on maintenance treatment in adults and adolescents 12 years and older with severe asthma who are inadequately controlled despite high dose inhaled corticosteroids plus another medicinal product for maintenance treatment. Asthma is a chronic inflammatory disease of the airways characterised by airflow obstruction and bronchospasms.
Although the etiology of the disease is unknown, environmental, genetic and psychogenic factors seem to contribute. Tezspire is a monoclonal antibody targeting the thymic stromal lymphopoietin (TSLP), a cytokine involved in the maturation of T lymphocytes. By inhibiting the binding of TSLP to its receptor, Tezspire blocks TSLP-mediated inflammation. For more information please consult the product for Tezspire on the EMA website.
Vabysmo (faricimab): is indicated for the treatment of adult patients with neovascular (wet) age-related macular degeneration (nAMD) and visual impairment due to diabetic macular oedema (DME).
Vascular endothelial growth factor A (VEGF-A) is the main protein responsible for the induction of blood vessel growth and, therefore, it is thought to contribute to the pathophysiology of retinal vascular diseases, such as nAMD and DME. Angiopoietin 2 (Ang-2) is a cytokine that, together with VEGF, promotes angiogenesis. Faricimab is a bispecific antibody that targets VEGF-A and Ang-2, thereby blocking the binding to their receptors. For more information please consult the product for Vabysmo on the EMA website.
Recommendations on extensions of therapeutic indication:
Genvoya (elvitegravir / cobicistat / emtricitabine / tenofovir alafenamide): extension of indication to the treatment of human immunodeficiency virus 1 (HIV-1) infection in paediatric patients aged from 2 years and with body weight at least 14 kg. Genvoya is already authorised for adults. For more information please consult the product for Genvoya on the EMA website.
Imcivree (setmelanotide): extension of indication to include the treatment of obesity and hunger control in patients with Bardet-Biedl syndrome in adults and children 6 years of age and older. Imcivree had previously been authorised for the treatment of obesity and the control of hunger associated with other genetic disorders. For more information please consult the product for Imcivree on the EMA website.
Imvanex (live modified vaccinia virus Ankara): extension of indication to include the active immunisation against monkeypox and disease caused by vaccinia virus in adults. Imvanex had previously been authorised for the active immunisation against smallpox. For more information please see the EMA news announcement on Imvanex. For more information please consult the product for Imvanex on the EMA website.
Retsevmo (selpercatinib): extension of indication to the first line treatment of adults and adolescents 12 years and older with advanced RET mutant medullary thyroid cancer. Retsevmo had previously been authorised for the treatment of non-small cell lung cancer and thyroid cancer. For more information please consult the product for Retsevmo on the EMA website.
Tecartus (brexucabtagene autoleucel): extension of indication to the treatment of adult patients 26 years of age and above with relapsed or refractory B-cell precursor acute lymphoblastic leukaemia. Tecartus had previously been authorised for the treatment of mantle cell lymphoma. Tecartus is an advanced therapy medicinal product (ATMP). For more information please consult the product for Tecartus on the EMA website.
Ultomiris (ravulizumab): extension of indication as an add-on to standard therapy for the treatment of adult patients with generalised myasthenia gravis who are anti-acetylcholine receptor antibody-positive. Ultomiris had previously been authorised for the treatment of paroxysmal nocturnal haemoglobinuria and atypical haemolytic uraemic syndrome. For more information please consult the product for Ultomiris 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:
Filsuvez (birch bark extract): is indicated for the treatment of partial thickness wounds associated with dystrophic and junctional epidermolysis bullosa in patients 6 months and older. EPAR Filsuvez.
Valneva (COVID-19 vaccine [inactivated, adjuvanted, adsorbed]): is indicated for active immunisation to prevent COVID-19 caused by SARS-CoV-2 in individuals 18 to 50 years of age. EPAR Valneva.
Yselty (linzagolix choline): is indicated for the treatment of moderate to severe symptoms of uterine fibroids in adult women of reproductive age. EPAR Yselty.
Recently started procedures:
Sars-cov-2 prefusion spike delta tm protein, recombinant - Active immunisation to prevent COVID-19 caused by SARS-CoV-2 in individuals 18 years of age and older.
Other topics of interest:
Update on the following authorised medicines for the treatment or prevention of COVID-19:
The CHMP recommended extending the use of Spikevax as a booster in adolescents from 12 to 17 years of age. Spikevax (elasomeran / COVID-19 mRNA vaccine [nucleoside-modified]) is indicated for active immunisation to prevent COVID-19 caused by SARS-CoV-2 in individuals 6 years of age and older.
Veklury (remdesivir): has been recommended for switch from CMA to standard authorisation. Veklury is indicated for the treatment of coronavirus disease 2019 (COVID-19) in:
- adults and adolescents (aged 12 to less than 18 years and weighing at least 40 kg) with pneumonia requiring supplemental oxygen (low- or high-flow oxygen or other non-invasive ventilation at start of treatment).
- adults who do not require supplemental oxygen and who are at increased risk of progressing to severe COVID-19.
After receiving a conditional marketing authorisation in July 2020, the CHMP has now recommended granting a full marketing authorisation to Veklury, following the submission of data that fulfils the last outstanding specific obligation.