DUBLIN – The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) closed out its year’s work with positive opinions on two applications, Novartis AG’s Beovu (brolucizumab) in wet age-related macular degeneration (AMD) and Merck & Co. Inc.’s Recarbrio for treating gram-negative infections in adults.

It was a relatively calm end to what has been a momentous year for the EMA, during which it closed the doors on its London headquarters of 24 years and crossed the North Sea to its new home in Amsterdam. Amid all the Brexit-induced turmoil that has shaken the very foundations of the agency, it has issued positive recommendations for 41 new medicines, as well as five biosimilar products and the usual batch of generics. All but the most recent of these opinions have led to formal European Commission approvals – the bureaucratic lag of 67 days between a CHMP recommendation and final sign-off is still in place.

The Beovu nod follows an FDA approval for the product in October. The molecule, a single-chain antibody fragment that binds all isoforms of vascular endothelial growth factor A (VEGF-A), works by blocking endothelial cell reproduction, which inhibits the growth of new blood vessels in the eye during the neovascular or advanced stage of the condition. It is pitched squarely at the multibillion-dollar franchise Bayer AG, of Leverkusen, Germany, and Regeneron Pharmaceuticals Inc., of Tarrytown, New York, have built around Eylea (aflibercept). The latter gained approval in wet AMD in 2011 but has since picked up approvals in several other indications.

Beovu gained approval based on being non-inferior to Eylea. It also appears to reduce the incidence of cataract formation (7% vs. 11% for Eylea) in head-to-head phase III studies. Its drawbacks include a higher incidence of intraocular inflammation (4% vs. 1%) and immunogenicity problems arising from its rabbit origin.

In the U.S., Novartis has priced Beovu slightly below the cost of Eylea ($1,850 vs $1,941 per vial). European pricing will be considerably less, although reimbursement will be negotiated on the usual country-by-country basis, and unambiguous pricing information is not likely to be forthcoming. The transparency that EMA has labored hard to adopt in its operations is not replicated within the commercial sphere.

Kenilworth, N.J.-based Merck gained FDA approval in July for Recarbrio, a fixed-dose combination of imipenem, a carbapenem antibiotic, cilastatin, a renal dehydropeptidase inhibitor that prevents renal metabolism of imipenem and prolongs the drug’s effects, and relebactam, a beta lactamase inhibitor that tackles one form of emergent resistance. The approval is broader than that the FDA offered – it is intended for adults with gram positive infections who have limited treatment options. The FDA label stipulates that it is indicated for complicated urinary tract infections or complicated intra-abdominal infections.

Fewer than 2018

The 2019 total is in some ways behind last year’s tally, when the CHMP voted in favor of 53 new drugs and another 15 biosimilars. (These numbers omit generic, informed-consent, hybrid and pediatric use marketing authorizations). The writing was on the wall several months ago, when the CHMP transferred several applications from its accelerated assessment procedure to a standard review. Brexit has taken a severe toll on the EMA’s capacity.

Novartis, of Basel, Switzerland, clocked the largest number of positive opinions with four, although one of these, the Cushing’s syndrome drug Isturisa (osilodrostat) was passed to Milan, Italy-based Recordati SpA, as part of a larger transaction involving the sale of two marketed endocrine drugs. Pfizer Inc., of New York, gained three positive opinions, all for cancer drugs, as well as a fourth for its adalimumab biosimilar.

In all, seven antibody drugs received CHMP recommendations during 2019, along with five biosimilars. Three of the latter included various versions of adalimumab, Abbvie Inc.’s blockbuster TNF-alpha inhibitor, which it markets in multiple autoimmune indications as Humira. Fresenius Kabi AG, of Bad Homburg, Germany, is responsible for two of them, which it has branded as Idacio and Kromeya, while Pfizer picked up an approval for Amsparity. The other two biosimilars are both versions of pegfilgrastim, which is indicated for chemotherapy-associated neutropenia. One, Grasustek, is marketed by Juta Pharma GmbH, of Flensburg, Germany, while the other, Pegfilgrastim Mundipharma, comes from Cambridge, UK-based Mundipharma International Ltd.

Just one advanced therapeutic medicinal product (ATMP) received a positive recommendation in 2019, Cambridge, Mass.-based Bluebird Bio Inc.’s Zynteglo (autologous CD34+ cells encoding betaA-T87Q-globin gene) gene therapy for beta-thalassemia. Two ATMPs were backed in 2018, the CD19-direct CAR T therapies Kymriah (tisagenlecleucel) and Yescarta (axicabtagene ciloleucel) developed by Novartis and Kite Pharma (now part of Foster City, Calif.-based Gilead Sciences Inc.). However, a third advanced therapy, Luxturna (voretigene neparvovec), a gene therapy developed by Spark Therapeutics Inc. and Novartis, navigated through the regulatory process with an orphan drug instead of an ATMP designation.

Zynteglo was among three products to graduate from the EMA’s prime medicines scheme to receive a positive CHMP recommendation in 2019. The others included Ervebo (Ebola Zaire vaccine (rVSVΔG-ZEBOV-GP, live), developed by Merck and Polivy (polatuzumab vedotin), Basel-based Roche Holding AG’s antibody drug conjugate approved for diffuse large B-cell lymphoma.

The first CHMP meeting of 2020 will run from Jan. 27 through Jan. 30. By then, it will have moved into its permanent headquarters, having worked from temporary offices in Amsterdam since its initial move in March.

CHMP positive recommendations issued in 2019

Date Product Indication Marketing authorization holder
Jan. Ajovy (fremanezumab) Migraine Teva Pharmaceuticals Industries Ltd.
Vizimpro (dacomitinib Non-small-cell lung cancer Pfizer Inc.
Feb. Ondexxya (andexanet alfa) Anti-coagulant antidote Portola Pharmaceuticals Inc.
Palynziq (pegvaliase) Phenylketonuria Biomarin Pharmaceutical Inc.
Waylivra (volanesorsen) Familial chylomicronaemia syndrome Akcea Therapeutics Inc.
Zynquista (sotagliflozin) Type 1 diabetes Lexicon Pharmaceuticals Inc.
Skyrizi (risankizumab) Psoriasis Abbvie Inc.
Dectova (zanamivir) Influenza Glaxosmithkline plc
Lorviqua (lorlatinib) Non-small cell lung cancer Pfizer
Mar. Zynteglo (autologous CD34+ cells encoding betaA-T87Q-globin gene) Beta-thalassemia Bluebird Bio Inc.
Apr. Sixmo (buprenorphine implant) Opioid dependence Molteni Farmaceutici SpA
Esperoct (turoctocog alfa pegol) Hemophilia A Novo Nordisk A/S
Ultomiris (ravulizumab) Paroxysmal nocturnal haemoglobinuria Alexion Pharmaceuticals Inc.
Doptelet (avatrombopag) Thrombocytopenia Dova Pharmaceuticals Inc.
Dovato (dolutegravir / lamivudine) HIV Viiv Healthcare
Libtayo (cemiplimab) Cutaneous squamous cell carcinoma Sanofi SA, Regeneron Pharmaceuticals Inc.
Nuceiva (botulinum toxin type a) Glabellar (frown) lines Evolus Inc.
Talzenna (talazoparib) Breast cancer Pfizer Inc.
May Cufence (trientine dihydrochloride) Wilson’s disease Univar BV
LysaKare (Arginine/lysine) Kidney protection during radiation Novartis AG
Jun. Giapreza (angiotensin II) Shock-associated hypotension La Jolla Pharmaceutical Co.
Jul. Vitrakvi (larotrectinib) Solid tumors with an NTRK gene fusion Bayer AG
Epidyolex (cannabidiol) Lennox-Gastaut syndrome or Dravet syndrome GW Pharmaceuticals plc
Inbrija (inhaled levodopa) ‘Off’ periods in Parkinson’s disease Acorda Therapeutics Inc.
Trogarzo (ibalizumab-uiyk) HIV Theratechnologies Inc.
Aug. No meeting    
Sep. Xospata (gilteritinib) Acute myeloid leukaemia Astellas Pharma Inc.
Qtrilmet (metformin + saxagliptin + dapagliflozin) Type 2 diabetes Astrazeneca plc
Rhokiinsa (netarsudil) Glaucoma or ocular hypertension Aerie Pharmaceuticals Inc.
Oct. Ervebo (Ebola Zaire Vaccine (rVSVΔG-ZEBOV-GP, live)) Ebola virus immunization Merck & Co. Inc.
Baqsimi (intranasal glucagon) Severe hypoglycemia Eli Lilly & Co.
Quofenix (delafloxacin) Skin & skin structure infection Menarini Group
Rinvoq (upadacitinib) Rheumatoid arthritis Abbvie Inc.
Spravato (esketamine) Treatment-resistant depression Johnson & Johnson Co.
Evenity (romosozumab) Severe osteoporosis UCB SA
Nov. Isturisa (osilodrostat) Cushing’s syndrome Novartis AG
Mayzent (siponimod) Secondary progressive multiple sclerosis Novartis AG
Polivy (polatuzumab vedotin) Diffuse large B-cell lymphoma Roche Holding AG
Sunosi (solriamfetol) Narcolepsy Jazz Pharmaceuticals plc
Tavlesse (fostamatinib) Primary immune thrombocytopenia Rigel Pharmaceuticals Inc.
Dec. Beovu (brolucizumab) Wet age-related macular degeneration Novartis AG
Recarbrio (imipenem + cilastatin + relebactam) Aerobic gram-negative infection Merck & Co. Inc.
Sources: EMA, company websites
Note: Excludes biosimilar, informed-consent, generic and hybrid approvals

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