CHMP Meeting Highlights May 2021

Information about the Austrian representation on the CHMP and monthly updates can be found at this link.

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

• Actinic keratosis
• Cerebral adrenoleukodystrophy (CALD)
• Obesity (associated with deficiencies in the MC4R pathway)
• Obstructive sleep apnoea (excessive daytime sleepiness)
• Progressive familial intrahepatic cholestasis (PFIC)
• Chronic heart failure with reduced ejection fraction (HFrEF)
• 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 please consult the product page for Bylvay (odevixibat) on the EMA website.

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 (EOEO). Imcivree binds to and activates the MC4R, thereby reducing appetite and increasing resting metabolic rate. For more information please consult the product page for Imcivree (setmelanotide) on the EMA website.

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 please consult the product page for Klisyri (tirbanibulin mesylate) on the EMA website.

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 please consult the product page for Ozawade (pitolisant) on the EMA website.

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 (LH) and the follicle-stimulating hormone (FSH), 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 please consult the product page for Ryeqo (relugolix, estradiol, norethisterone acetate) on the EMA website.

Skysona (elivaldogene autotemcel) for the treatment of early cerebral adrenoleukodystrophy (CALD) for patients without a matched sibling haematopoietic stem cell donor. ALD is a rare X-linked metabolic disease and the cerebral presentation (CALD) 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 please consult the product page for Skysona (elivaldogene autotemcel) on the EMA website.

Verquvo (vericiguat) for the treatment of symptomatic chronic heart failure in adult patients with reduced ejection fraction (HFrEF). 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 please consult the product page for Verquvo (vericiguat) on the EMA website.

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 (ALL) as part of the consolidation therapy. For more information please consult the product page for Blincyto (blinatumomab) on the EMA website.

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 please consult the product page for Darzalex (daratumumab) on the EMA website.

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 (AL) amyloidosis. For more information please consult the product page for Darzalex (daratumumab) on the EMA website.

Eucreas (vildagliptin, metformin hydrochloride): the previously authorized indication has been revised. Eucreas is now indicated as an adjunct to diet and exercise to improve glycaemic control in adults with type 2 diabetes mellitus: in patients who are inadequately controlled with metformin hydrochloride alone; in patients who are already being treated with the combination of vildagliptin and metformin hydrochloride, as separate tablets; or in combination with other medicinal products for the treatment of diabetes, including insulin, when these do not provide adequate glycaemic control. For more information please consult the product page for Eucreas (vildagliptin, metformin hydrochloride) on the EMA website.

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 please consult the product page for Evotaz (atazanavir, cobicistat) on the EMA website.

Galvus (vildagliptin): the previously authorized indication has been revised. Galvus is now indicated as an adjunct to diet and exercise to improve glycaemic control in adults with type 2 diabetes mellitus: as monotherapy in patients in whom metformin is inappropriate due to contraindications or intolerance; or in combination with other medicinal products for the treatment of diabetes, including insulin, when these do not provide adequate glycaemic control. For more information please consult the product page for Galvus (vildagliptin) on the EMA website.

Icandra (vildagliptin, metformin hydrochloride): the previously authorized indication has been revised. Icandra is now indicated as an adjunct to diet and exercise to improve glycaemic control in adults with type 2 diabetes mellitus: in patients who are inadequately controlled with metformin hydrochloride alone; in patients who are already being treated with the combination of vildagliptin and metformin hydrochloride, as separate tablets; or in combination with other medicinal products for the treatment of diabetes, including insulin, when these do not provide adequate glycaemic control. For more information please consult the product page for Icandra (vildagliptin, metformin hydrochloride) on the EMA website.

Jalra (vildagliptin): the previously authorized indication has been revised. Jalra is now indicated as an adjunct to diet and exercise to improve glycaemic control in adults with type 2 diabetes mellitus: as monotherapy in patients in whom metformin is inappropriate due to contraindications or intolerance; or in combination with other medicinal products for the treatment of diabetes, including insulin, when these do not provide adequate glycaemic control. For more information please consult the product page for Jalra (vildagliptin) on the EMA website.

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 please consult the product page for Jardiance (empagliflozin) on the EMA website.

Keytruda (pembrolizumab): extension of indication to include, in combination with platinum and fluoropyrimidine based chemotherapy, the first-line treatment of patients with locally advanced unresectable or metastatic carcinoma of the oesophagus or HER-2 negative gastroesophageal junction adenocarcinoma in adults whose tumours express PD‑L1 with a CPS ≥ 10. Keytruda had previously been authorised, in combination or as monotherapy, for the treatment of melanoma, non-small cell lung carcinoma, classical Hodgkin lymphoma, urothelial carcinoma, head and neck squamous cell carcinoma, renal cell carcinoma and colorectal cancer. For more information please consult the product page for Keytruda (pembrolizumab) on the EMA website.

Libtayo (cemiplimab): extension of indication to include, as monotherapy, the treatment adult patients with locally advanced or metastatic basal cell carcinoma (laBCC or mBCC) who have progressed on or are intolerant to a hedgehog pathway inhibitor (HHI). For more information please consult the product page for Libtayo (cemiplimab) on the EMA website.

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 please consult the product page for Libtayo (cemiplimab) on the EMA website.

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, non-small cell lung cancer (NSCLC), malignant pleural mesothelioma (MPM), renal cell carcinoma (RCC), classical Hodgkin lymphoma (cHL), squamous cell cancer of the head and neck (SCCHN), urothelial carcinoma and oesophageal squamous cell carcinoma (OSCC). For more information please consult the product page for Opdivo (nivolumab) on the EMA website.

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 please consult the product page for Spherox (spheroids of human autologous matrix-associated chondrocytes) on the EMA website.

Xiliarx (vildagliptin): the previously authorized indication has been revised. Xiliarx is now indicated as an adjunct to diet and exercise to improve glycaemic control in adults with type 2 diabetes mellitus: as monotherapy in patients in whom metformin is inappropriate due to contraindications or intolerance; or in combination with other medicinal products for the treatment of diabetes, including insulin, when these do not provide adequate glycaemic control. For more information please consult the product page for Xiliarx (vildagliptin) on the EMA website.

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, non-small cell lung cancer (NSCLC), malignant pleural mesothelioma (MPM) and renal cell carcinoma (RCC). For more information please consult the product page for Yervoy (ipilimumab) on the EMA website.

Zomarist (vildagliptin, metformin hydrochloride): the previously authorized indication has been revised. Zomarist is now indicated as an adjunct to diet and exercise to improve glycaemic control in adults with type 2 diabetes mellitus: in patients who are inadequately controlled with metformin hydrochloride alone; in patients who are already being treated with the combination of vildagliptin and metformin hydrochloride, as separate tablets; or in combination with other medicinal products for the treatment of diabetes, including insulin, when these do not provide adequate glycaemic control. For more information please consult the product page for Zomarist (vildagliptin, metformin hydrochloride) on the EMA website.

Newly published EPARs

The EPAR (European public assessment report) is the main document where the 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 23 - May 20, 2021.

• Abiraterone Accord (abiraterone acetate) for the treatment of prostate cancer
• Evrysdi (risdiplam) for the treatment of spinal muscular atrophy (SMA)
• Pemazyre (pemigatinib) for the treatment of cholangiocarcinoma
• Jemperli (dostarlimab) for the treatment of endometrial cancer
• Sibnayal (potassium citrate, potassium hydrogen carbonate) for the treatment of distal renal tubular acidosis (dRTA)
• Thiotepa Riemser (thiotepa) for the use before transplantation of haematopoietic progenitor cells
• Alymsys (bevacizumab) for the treatment of colon cancer, breast cancer, non-small cell lung cancer (NSCLC), renal cell carcinoma, ovary or fallopian tube cancer and cervix cancer
• Retsevmo (selpercatinib) for the treatment of cancer cause by mutations in the RET gene (non-small cell lung cancer (NSCLC), thyroid and medullary thyroid cancer)

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 (EB) in patients from birth onwards
• Ganirelix - prevention of premature luteinising hormone (LH) surges in women undergoing controlled ovarian hyperstimulation (COH) for assisted reproduction techniques (ART)
• Gefapixant - treatment of refractory or unexplained chronic cough
• Difelikefalin - treatment of pruritus
• Oportuzumab monatox - reatment and prevention of recurrence of carcinoma-in-situ (CIS) of the urinary bladder and prevention of recurrence of high grade Ta and/or T1 papillary tumours
• Relugolix - treatment of adult patients with advanced prostate cancer
• Enfortumab vedotin - treatment of locally advanced (LA) or metastatic urothelial cancer (mUC)
• 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 (mTNBC)

Further inquiry note

basg_anfragen@basg.gv.at