CHMP Meeting Highlights May 2021
ARIn the month of May 2021, medicinal products for the following indications have received a positive opinion:
- Actinic keratosis
- Cerebral adrenoleukodystrophy
- Obesity (associated with deficiencies in the MC4R pathway)
- Obstructive sleep apnoea (excessive daytime sleepiness)
- Progressive familial intrahepatic cholestasis
- Chronic heart failure with reduced ejection fraction
- Symptoms of uterine fibroids
New medicines recommended for approval
Bylvay (odevixibat) has been recommended for a marketing authorization under exceptional circumstances for the treatment of progressive familial intrahepatic cholestasis (PFIC) in patients aged 6 months or older. PFIC includes several heterogeneous autosomal recessive diseases, which all present with intra-hepatic cholestasis and impaired bile acid secretion and transport. This results in the accumulation of bile components within the liver and their subsequent excretion into the circulatory system, leading to pruritus and jaundice. Bylvay inhibits IBAT (ileal bile acid transporter, a key active transporter for bile acid reabsorption), thereby reducing the uptake of bile acids into the liver. For more information see EPAR Bylvay.
Imcivree (setmelanotide) for the treatment of obesity and the control of hunger associated with genetic deficiencies of the melanocortin 4 receptor (MC4R) pathway. The MC4R pathway is a hypothalamic neuroendocrine pathway, which regulates energy homeostasis and satiety. Genetic defects within this pathway are very rare and result in polyphagia and early-onset extreme obesity. Imcivree binds to and activates the MC4R, thereby reducing appetite and increasing resting metabolic rate. For more information see EPAR Imcivree.
Klisyri (tirbanibulin mesylate) for the field treatment of non-hyperkeratotic, non-hypertrophic actinic keratosis. Actinic keratosis is a pre-cancerous lesion of the skin induced by UV light. It presents as erythematous patches on the skin and can occur as single or multiple lesions. By binding to tubulin and disrupting the microtubule cytoskeleton, Klisyri induces cell-cycle arrest and apoptosis, acting as a potent anti-proliferative and anti-tumour agent. For more information see EPAR Klisyri.
Ozawade (pitolisant) for the treatment of excessive daytime sleepiness in obstructive sleep apnoea (OSA). OSA produces sleep disturbances that translate into loss of sleep, resulting in excessive daytime sleepiness (EDS). EDS and fatigue are the most common symptoms in OSA patients and have disabling consequences that impair a normal daily life. Ozawade increases the activity of brain histaminergic neurons, an important arousal system, by blocking histamine auto-receptors. Furthermore, it increases the release of acetylcholine, noradrenaline and dopamine in the brain. For more information see EPAR Ozawade.
Ryeqo (relugolix, estradiol, norethisterone acetate) for the treatment of symptoms of uterine fibroids in adult women of reproductive age. Uterine fibroids are benign hormone-sensitive tumours of the uterus. The most troublesome symptoms are heavy menstrual bleeding and pain. Ryeqo reduces the release of the luteinizing hormone and the follicle-stimulating hormone, which translates into a reduction of oestrogen and progesterone levels. Since this can induce symptoms of menopause, Ryeqo compensates this loss and, therefore, reduces these symptoms. For more information see EPAR Ryeqo.
Skysona (elivaldogene autotemcel) for the treatment of early cerebral adrenoleukodystrophy (cerebral ALD) for patients without a matched sibling haematopoietic stem cell donor. ALD is a rare X-linked metabolic disease and the cerebral presentation is the most severe form. The peroxisomal transport ALD protein (ALDP) is involved in the degradation pathway of very long chain fatty acids (VLCFA). In ALD patients, dysfunction or lack of this protein leads to accumulation of VLCFA in the central nervous system. The subsequent demyelination translates into an irreversible loss of neurological function. Skysona is a gene therapy consisting of transduced autologous cells carrying the gene for ALDP. As a gene therapy, the CHMP based its positive opinion on an assessment by the Committee for Advanced Therapies (CAT). For more information see EPAR for Skysona.
Verquvo (vericiguat) for the treatment of symptomatic chronic heart failure in adult patients with reduced ejection fraction. Heart failure is associated with an impaired synthesis of nitric oxide, which leads to a decreased activity of soluble guanylate cyclase (sGC) and a subsequent deficiency of cGMP. This contributes to disease progression in HFrEF patients, since cGMP deficiencies lead to myocardial and vascular dysfunction. Verquvo stimulates sGC and thereby increases the intracellular levels of cGMP For more information see EPAR Verquvo.
Recommendations on extensions of therapeutic indication
Blincyto (blinatumomab): extension of indication to include, as monotherapy, the treatment of paediatric patients aged 1 year or older with high-risk first relapsed Philadelphia chromosome negative CD19 positive B-precursor acute lymphoblastic leukaemia as part of the consolidation therapy. For more information see EPAR for Blincyto.
Darzalex (daratumumab): extension of indication to include, in combination with pomalidomide and dexamethasone, the treatment of adult patients with multiple myeloma who have received one prior therapy containing a proteasome inhibitor and lenalidomide and were lenalidomide-refractory, or who have received at least two prior therapies that included lenalidomide and a proteasome inhibitor and have demonstrated disease progression on or after the last therapy. For more information see EPAR for Darzalex.
Darzalex (daratumumab): extension of indication to include, in combination with cyclophosphamide, bortezomib and dexamethasone, the treatment of adult patients with newly diagnosed systemic light chain amyloidosis. For more information see EPAR for Darzalex.
Evotaz (atazanavir, cobicistat): extension of indication to include the treatment of adolescents (aged 12 years and older weighing at least 35 kg). For more information see EPAR for Evotaz.
Jardiance (empagliflozin): extension of indication to include the treatment of adults with symptomatic chronic heart failure with reduced ejection fraction. Jardiance had previously been authorised for the treatment of type 2 diabetes mellitus. For more information see EPAR for Jardiance.
Libtayo (cemiplimab): extension of indication to include, as monotherapy, the treatment adult patients with locally advanced or metastatic basal cell carcinoma who have progressed on or are intolerant to a hedgehog pathway inhibitor. For more information see EPAR for Libtayo.
Libtayo (cemiplimab): extension of indication to include, as monotherapy, the first-line treatment of adult patients with non-small cell lung cancer (NSCLC) expressing PD-L1 (in ≥ 50% tumour cells), with no EGFR, ALK or ROS1 aberrations, who have: locally advanced NSCLC who are not candidates for definitive chemoradiation, or metastatic NSCLC. For more information see EPAR for Libtayo.
Opdivo (nivolumab): extension of indication to include, in combination with ipilimumab, the treatment of adult patients with mismatch repair deficient or microsatellite instability high metastatic colorectal cancer after prior fluoropyrimidine based combination chemotherapy. Opdivo had previously been authorised, in combination or as monotherapy, for the treatment of melanoma, NSCLC, malignant pleural mesothelioma, renal cell carcinoma, classical Hodgkin lymphoma, squamous cell cancer of the head and neck, urothelial carcinoma and oesophageal squamous cell carcinoma. For more information see EPAR for Opdivo.
Spherox (spheroids of human autologous matrix-associated chondrocytes): extension of indication to include the treatment of adolescents with closed epiphyseal growth plate in the affected joint. For more information see EPAR for Spherox.
Yervoy (ipilimumab): extension of indication to include, in combination with nivolumab, the treatment of adult patients with mismatch repair deficient or microsatellite instability high metastatic colorectal cancer after prior fluoropyrimidine based combination chemotherapy. Yervoy had previously been authorised, in combination or as monotherapy, for the treatment of melanoma, NSCLC, malignant pleural mesothelioma and renal cell carcinoma. For more information see EPAR for Yervoy.
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 between April 23rd and May 20th 2021:
Abiraterone Accord (abiraterone acetate) for the treatment of prostate cancer, see EPAR Abiraterone accord.
Evrysdi (risdiplam) for the treatment of spinal muscular atrophy, see EPAR Evrysdi.
Pemazyre (pemigatinib) for the treatment of cholangiocarcinoma, see EPAR Pemazyre.
Jemperli (dostarlimab) for the treatment of endometrial cancer, see EPAR Jemperli.
Sibnayal (potassium citrate, potassium hydrogen carbonate) for the treatment of distal renal tubular acidosis, see EPAR Sibnayal.
Thiotepa Riemser (thiotepa) for the use before transplantation of haematopoietic progenitor cells, see EPAR Thiotepa Riemser.
Alymsys (bevacizumab) for the treatment of colon cancer, breast cancer, non-small cell lung cancer, renal cell carcinoma, ovary or fallopian tube cancer and cervix cancer, see EPAR Alymsys.
Retsevmo (selpercatinib) for the treatment of cancer cause by mutations in the RET gene (non-small cell lung cancer, thyroid and medullary thyroid cancer), see EPAR Retsevmo.
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:
- Dengue tetravalent vaccine (live, attenuated) under Article 58 - prevention of dengue disease.
- Dengue tetravalent vaccine (live, attenuated) - prevention of dengue disease.
- Betulae cortex dry extract (5-10:1; extraction solvent: n-heptane 95% (w/w)) - treatment to achieve accelerated healing of wounds associated with dystrophic and junctional epidermolysis bullosa in patients from birth onwards.
- Ganirelix - prevention of premature luteinising hormone surges in women undergoing controlled ovarian hyperstimulation for assisted reproduction techniques.
- Gefapixant - treatment of refractory or unexplained chronic cough.
- Difelikefalin - treatment of pruritus.
- Oportuzumab monatox - reatment and prevention of recurrence of carcinoma-in-situ of the urinary bladder and prevention of recurrence of high grade Ta or T1 papillary tumours.
- Relugolix - treatment of adult patients with advanced prostate cancer.
- Enfortumab vedotin - treatment of locally advanced or metastatic urothelial cancer.
- Daridorexant - treatment of insomnia.
- Teriparatide - treatment of osteoporosis.
- Sugammadex - reversal of neuromuscular blockade induced by rocuronium or vecuronium.
- Sacituzumab govitecan - treatment of unresectable locally advanced or metastatic triple-negative breast cancer.