42 New Substances Among 84 EU Approval Recommendations In 2018
Executive Summary
The EMA’s CHMP recommended EU marketing authorization for a total of 84 new drugs in 2018, containing a total of 42 new active substances. They included the EU’s first two CAR-T cell therapies, Kymriah and Yescarta, which were also among the 21 orphan medicines to gain a positive opinion from the committee.
The European Medicines Agency’s drug evaluation committee, the CHMP, recommended 84 new medicines for EU approval in 2018, down from 92 in 2017. They included products containing a total of 42 new active substances, compared with 35 NAS in the previous year.
Among the drugs given a positive opinion by the CHMP were three advanced therapy medicines – Novartis AG’s Kymriah (tisagenlecleucel) and Gilead Sciences Inc.’s Yescarta (axicabtagene ciloleucel) for blood cancers, and Spark Therapeutics Inc.’s Luxturna (voretigene neparvovec) for inherited retinal dystrophy. Kymriah and Yescarta were among the 21 orphan drugs to be OKd by the committee, and were also the first CAR-T cell therapies to gain an EU marketing authorization.
Four of the 84 products were reviewed under accelerated assessment, while three were recommended for approval under exceptional circumstances and one for a conditional marketing authorization.
Last year the CHMP also advised against the approval of five products, and 10 marketing authorization applications were withdrawn.
23 of the new drugs recommended for approval were for cancer indications, including Kymriah and Yescarta, as well as Takeda Pharmaceutical Co. Ltd.’s Alunbrig (brigatinib) and AstraZeneca PLC’s Imfinzi (durvalumab), both for NSCLC, and Puma Biotechnology Inc.’s Nerlynx (neratinib) for breast cancer.
CHMP opinions are sent to the European Commission, which makes a final, legally binding decision on marketing authorization, usually within 67 days.
The positive and negative opinions delivered by the CHMP in 2018, as well as new products filed with the EMA and marketing authorizations granted by the European Commission, were monitored extensively by the Pink Sheet throughout the year in articles that provided a deep dive into each of the CHMP’s monthly meetings and in our various performance trackers. (Also see "European CHMP Opinions And MAA Updates" - Pink Sheet, 18 Dec, 2018.) (Also see "New EU Approvals" - Pink Sheet, 30 Nov, 2018.) (Also see "New Filings At The EMA" - Pink Sheet, 3 Jan, 2019.)
Other Product Classes
11 products for infectious diseases received the CHMP green light, as did 10 neurologicals, nine hematological drugs, and seven products in the immunology/rheumatology/transplantation category.
The anti-infectives included Gilead’s HIV drug Biktarvy (bictegravir in combination) and TetraPhase Pharmaceuticals Inc.’s Xerava (eravacycline) for intra-abdominal infections. Among the important new neurological drugs were Alnylam Pharmaceuticals Inc.’s Onpattro (patisiran) and Ionis Pharmaceuticals Inc./Akcea Therapeutics Inc.’s Tegsedi (inotersen), both for hereditary transthyretin amyloidosis, and two analgesics for migraine prophylaxis: Lilly Research Laboratories’s Emgality (galcanezumab) and Novartis’s Aimovig (erenumab).
Two hemophilia A drugs – Bayer AG’s Jivi (damoctocog alfa pegol) and Roche/Chugai Pharmaceutical Co. Ltd.’s Hemlibra (emicizumab) – were among the hematology medicines OKd by the CHMP.
As for special approval pathways, Onpattro, Tegsedi and Hemlibra underwent an accelerated assessment by the committee, as did
Shire PLC’s Takhzyro (lanadelumab) for hereditary angioedema. The fast-track mechanism can cut the time it takes the CHMP to evaluate a marketing authorization application from up to 210 days to up to 150 days (not counting clock stops when applicants have to provide additional information).
The products that were recommended for approval under exceptional circumstances were Chiesi Farmaceutici SPA’s Lamzede (velmanase alfa) for alpha mannidosis, Aegerion Pharmaceuticals Inc.’s Myalepta (metreleptin) for leptin deficiency in lipodystrophy, and
Ultragenyx Pharmaceutical Inc.’s Mepsevii (vestronidase alfa) for mucopolysaccharoidosis VII. Exceptional circumstances approvals are granted where the applicant is unable to provide comprehensive safety and efficacy data because the condition is rare or the collection of full information is not possible or is unethical.
Only one product received a positive opinion for a conditional approval: Clovis Oncology Inc.’s Rubraca (rucaparib) for ovarian neoplasms. A conditional approval requires the applicant to provide further data so that it can be converted into a full marketing authorization.
A full analysis of the EU NAS granted a marketing authorization by the commission in 2018 will be published shortly, as will a breakdown of new biosimilar marketing authorizations.
Safety Advice Issued
During 2018, the EMA also issued safety advice relating to a range of pharmaceutical products, including the removal from the market of multiple sclerosis drugs containing daclizumab because of “serious and sometimes fatal cases of autoimmune encephalitis." (Also see "EMA Calls For Zinbryta's ‘Immediate’ Suspension After More Reports of Brain Disorders" - Pink Sheet, 7 Mar, 2018.)
It recommended the suspension of some quinolone and fluoroquinolone antibiotics and restrictions on the use of all other such products after a review of “disabling and potentially permanent side-effects.” (Also see "EMA Acts On Patient Concerns Over Fluoroquinolone Antibiotics" - Pink Sheet, 8 Oct, 2018.)
It also advised introducing new measures to avoid the exposure of babies to valproate medicines in the uterus, and restrictions on the use of retinoid medicines during pregnancy.
New measures were recommended to minimize the risk of rare but serious liver injury with the uterine fibroid treatment Esmya (ulipristal acetate, Gedeon Richter), to restrict the use of Merck & Co. Inc.'s Keytruda (pembrolizumab) and Roche's Tecentriq (atezolimumab) in urothelial cancer, and to restrict the use of Bayer's Xofigo (radium-223 dichloride) in patients with metastatic prostate cancer because of the risk of early death and fracture.
From the editors of Scrip Regulatory Affairs.