Seven New Drugs Approved In EU In First Two Months of 2018
Executive Summary
Seven products containing a new active substance were approved in Europe in the first two months of 2018: Shire's Adynovi and Roche/Chugai's Hemlibra for hemophilia A, Roche's Ocrevus for multiple sclerosis, Kyowa Kirin's Crysvita for hypophosphatemia, AstraZeneca's Fasenra for asthma, Novo Nordisk's Ozempic for diabetes, and MSD's Prevymis for prophylaxis of cytomegalovirus infection.
In the first two months of 2018, seven products containing a new active substance received marketing authorizations through the EU's centralized procedure, including two treatments for hemophilia, new drugs for multiple sclerosis and diabetes, and two medicines for rare diseases – one for X-linked hyperphosphatemia, the other for preventing cytomegalovirus reactivation.
The two hemophilia drugs given the green light by the European Commission are Roche/Chugai's Hemlibra (emicizumab) and Shire's Adynovi (rurioctocog alfa pegol).
Hemlibra was authorized very quickly following the approval recommendation from the European Medicines Agency's key scientific committee, the CHMP, which announced its positive opinion just a month ago, on January 26. (Also see "Seven Green Lights From EU’s CHMP, Including Drugs For Hemophilia, Diabetes, Alpha Mannosidosis And Hyperkalemia" - Pink Sheet, 26 Jan, 2018.) CHMP opinions are forwarded to the commission for a legally binding decision valid throughout the EU. The commission, which usually follows the CHMP's advice, has 67 days in which to make its decision.
Hemlibra is indicated for routine prophylaxis of bleeding episodes in hemophilia A patients of all age groups with factor VIII inhibitors. Almost one in three people with severe hemophilia A can develop inhibitors to factor VIII replacement therapies, putting them at greater risk of life-threatening bleeds or repeated bleeding episodes that can cause long-term joint damage, the companies noted. Hemlibra was reviewed under accelerated assessment, a fast-track procedure for medicines that the CHMP believes are of major interest for public health and therapeutic innovation.
Adynovi is authorized for the treatment and prophylaxis of bleeding in hemophilia A patients 12 years and above. The approval was based on outcomes from three Phase III clinical trials: a prospective, global, multi-center, open label, non-randomized study of patients aged 12 to 65; a prospective, uncontrolled, open label, multi-center study of patients 12 years and younger; and a study of perioperative control of hemostasis with interim study results from 15 patients with severe hemophilia A undergoing surgical procedures. The product was first approved as Adynovate in the US, followed by Japan, Canada, and Colombia, and it is also approved as Adynovi in Switzerland.
Roche's Ocrevus (ocrelizumab) was approved for relapsing forms of multiple sclerosis (MS) and, more significantly, primary progressive MS, making it the first approved disease-modifying medicine for both forms to get the go-ahead in the EU. MS affects 700,000 people in Europe and around 96,000 have the highly disabling primary progressive form. However, the approval covers only early-stage and not all primary progressive MS patients. In its positive opinion in November, the CHMP said that data from the clinical trial in the primary progressive group showed patients in the early stage of disease benefited more and that "more investigation is needed to better understand how beneficial Ocrevus might be in the more advanced stages of the disease." (Also see "All Systems Go as Roche MS Drug Ocrevus Secures EU Okay At Last" - Scrip, 12 Jan, 2018.)
Novo Nordisk's diabetes drug Ozempic (semaglutide) is the latest once-weekly GLP-1 agonist to be available for type 2 disease. It is indicated as monotherapy for diabetes mellitus in adults when metformin is considered inappropriate due to intolerance or is contraindicated, and as an addition to other medicinal products for the treatment of diabetes. Ozempic has been approved for use in the EU in a multi-dose Ozempic pen, the latest generation of Novo Nordisk prefilled devices. However, the product will not be launched just yet: the company said it intends to submit a variation application to the EMA for the approval of an updated pen that will "help facilitate reimbursement for patients with type 2 diabetes using Ozempic." Launch is expected in the first EU countries in the second half of 2018 once the variation application is approved. The company has also committed to conducting post-approval safety studies on semaglutide, including a long-term diabetic retinopathy outcome study. (Also see "Semaglutide's CHMP Backing Stipulates Post-Approval Safety Studies" - Scrip, 15 Dec, 2017.) The product, which was approved in the US last December, is expected to be a blockbuster for the Danish company. (Also see "Novo Nordisk To Target 'New GLP-1 Patients Only' With Weekly Ozempic " - Scrip, 25 Feb, 2018.)
Two Orphan Drugs
Crysvita (burosumab) is an orphan drug from Kyowa Kirin for the treatment of X-linked hypophosphatemia (XLH) with radiographic evidence of bone disease in children one year of age and older and adolescents with growing skeletons. The product is a human monoclonal antibody that binds to and inhibits the activity of fibroblast growth factor 23. According to the EMA, the benefits of Crysvita are its ability to reduce the loss of phosphate from the kidney, to improve abnormally low serum phosphate concentrations, and to reduce the severity of rickets as shown in X-rays.The product has received a conditional marketing authorization, meaning that Kyowa Kirin will need to provide further data if it is to secure a full MA.
The other rare disease product approved is MSD's Prevymis (letermovir), for the prophylaxis of cytomegalovirus reactivation and disease in adult CMV-seropositive recipients [R+] of an allogeneic hematopoietic stem cell transplant. The product is a member of the new class of non-nucleoside CMV inhibitors (3,4 dihydro-quinazolines) that inhibits viral replication by specifically targeting the viral terminase complex. It was developed by AiCuris (founded in 2006 as a spin-off from Bayer) up to the Phase IIb stage, and in 2012 it was licensed to MSD, which has worldwide development and commercialization rights, the companies said.
Fasenra For Asthma
AstraZeneca's Fasenra (benralizumab) is to be used as add-on maintenance treatment in adults with severe eosinophilic asthma that is inadequately controlled despite high-dose inhaled corticosteroids plus long acting beta-agonists. The company said the approval was based on the Phase III WINDWARD program, including the pivotal Phase III exacerbation trials, SIROCCO and CALIMA, and the Phase III OCS-sparing trial, ZONDA. These showed "significant reductions in asthma exacerbations, improvements in lung function and reductions in oral corticosteroid use from baseline, versus placebo, AstraZeneca said, adding that Fasenra is "the first-ever approved respiratory biologic medicine with an 8-week maintenance dosing schedule.” The product was approved in the US last November.
Table 1: EU NAS approvals in first two months of 2018.
|
Name |
Company | Indication | Approval Date |
| Adynovi (rurioctocog alfa pegol) | Shire | hemophilia A | January 8 |
| Crysvita (burosumab) | Kyowa Kirin | hypophosphatemia | February 19 |
| Fasenra (benralizumab) | AstraZeneca | eosinophilic asthma | January 8 |
| Hemlibra (emicizumab) | Roche/Chugai | hemophilia A | February 23 |
| Ocrevus (ocrelizumab) | Roche | multiple sclerosis | January 8 |
| Ozempic (semaglutide) | Novo Nordisk | diabetes | February 8 |
| Prevymis (letermovir) | MSD | cytomegalovirus prevention | January 8 |
Other Approvals
Other products approved in January and February included Dr Falk's budesonide-containing product Jorveza, which has orphan designation for eosinophilic esophagitis and was assessed under the accelerated procedure; Intrarosa/Endoceutics Ltd's prasterone product for vulvar and vaginal atrophy in postmenopausal women with moderate to severe symptoms; and Diurnal/Alkindi's hydrocortisone for replacement therapy in adrenal insufficiency.
Also getting the green light were two biosimilars: Amgen's Mvasi (bevacizumab), the first EU biosimilar version of Roche’s Avastin, and Celltrion's Herzuma (trastuzumab), the second biosimilar of Roche’s Herceptin.
From the editors of Scrip Regulatory Affairs.