Zero Success For Companies Appealing Negative CHMP Opinions In EU Last Year
Executive Summary
All five of the appeals against negative opinions for new drug applications that the European Medicines Agency completed last year met with failure. On the positive side, 92 new medicines were granted positive opinions, of which 35 contained new active substances.
Last year, five appeals against negative opinions delivered by the European Medicines Agency on initial marketing authorization applications were completed, and all five failed.
The EMA’s key scientific committee, the CHMP, handed down a total of six negative opinions relating to initial MAAs last year, according to newly published highlights of agency activities relating to medicines in 2017. The sponsors of all six products requested a re-examination by the CHMP of its original opinions.
The five completed re-examinations failed to secure a positive opinion; the sixth is just getting under way. By contrast, both of the two negative opinions that were issued in 2016 were converted to positive opinions following re-examination.
On a more positive note, 92 new medicines received a positive recommendation for approval from the CHMP last year, up from 81 in 2016. “Many of these medicines represent a significant improvement in their therapeutic areas; they include medicines for children, for rare diseases and advanced therapies,” the EMA said.
The five negative opinions that were upheld related to MAAs for the following products:
- Helsinn Birex Pharmaceuticals Ltd’s Adlumiz (anamorelin hydrochloride) for treating anorexia, cachexia or unintended weight loss in patients with non-small cell lung cancer.
- Vanda Pharmaceuticals Inc’s Fanaptum (iloperidone) for schizophrenia.
- XBiotech Inc’s Xilonix (human IgG1 monoclonal antibody specific for human interleukin-1 alpha) for treating debilitating symptoms of advanced colorectal cancer.
- AB Science’s Masipro (masitinib) for the treatment of systemic mastocytosis.
- Nektar Therapeutics’ Onzeald (etirinotecan pegol) for breast cancer with brain metastases.
The MAAs were subsequently rejected by European Commission, which considers the opinions of the CHMP and has the final say on marketing authorization for the EU.
The sixth negative opinion – on PharmaMar SA’s Aplidin (plitidepsin) for multiple myeloma – was adopted in December 2017. The company has appealed; rapporteurs for the re-examination are being appointed and a draft timetable for the re-examination is being agreed. (Also see "Roche’s Hemlibra Looking For CHMP Green Light, Crunch Time for Santhera DMD Hopeful" - Pink Sheet, 23 Jan, 2018.) Applicants have the right to request a re-examination of a negative opinion within 15 days of receipt of the notification.
Positive Opinions
Of the 92 medicines that received a positive CHMP opinion, two were advanced therapy medicinal products (ATMPs), 35 contained new active substances, and 19 were orphan medicines.
The two ATMPs were TiGenix’sAlofisel (darvadstrocel; Cx601), which was granted a positive opinion in December, and CO.DON AG’sSpherox, which has now been approved.
Alofisel is designed to treat complex perianal fistulas in patients with Crohn’s disease. Spherox (spheroids of human autologous matrix associated chondrocytes) is for the treatment of symptomatic articular cartilage defects in the knee.
A total of 23 of the 92 products that received a positive recommendation for approval were for treating cancer. The remaining products were for conditions that fall under the therapeutic areas of infections (15 products), endocrinology (12), immunology/rheumatology/transplantation (11), neurology (10), uro-nephrology (4), hematology/hemostaseology (4), pneumology/allergology (5), dermatology (3), hepatology/gastroenterology (2), and metabolism (2). In addition, one drug fell under the cardiovascular category – Daiichi Sankyo Co. Ltd’s anticoagulant Roteas (edoxaban).
Some 19 products had an orphan designation at the time of the CHMP’s positive opinion. According to the EMA, new orphan medicines with the potential to significantly benefit patients included Dompe SPA’sOxervate (cenegermin eye drops) for the treatment of neurotrophic keratitis, EUSA Pharma/Apeiron Biologics AG’s Qarziba (previously dinutuximab beta apeiron) for high-risk neuroblastoma, and Ipsen’s Xermelo (telotristat) for carcinoid syndrome.
Qarziba was also one of two products to gain a positive recommendation under the EMA’s exceptional circumstances pathway. The exceptional circumstances route allows patients access to medicines that cannot be approved under a standard authorization as comprehensive data cannot be obtained, either because there are only very few patients with the disease, or the collection of complete information on the efficacy and safety of the medicine would be unethical, or there are gaps in the scientific knowledge. The other drug is BioMarin Pharmaceutical Inc’sBrineura (cerliponase alfa) for treating neuronal ceroid lipofuscinosis type 2 (CLN2) disease.
Seven Drugs Get Fast-Tracked
Seven medicines received a recommendation for marketing authorization following an accelerated assessment (AA) procedure.
This fast-track mechanism is reserved for medicines that address unmet medical needs, allowing assessment potentially within 150 days rather than 210. The seven drugs are Biogen’sSpinraza (nusinersen) fortreating spinal muscular atrophy, Santen Inc’s Verkazia (ciclosporin) for severe vernal keratoconjunctivitis in children and adolescents, AbbVie Inc’sMaviret (glecaprevir/pibrentasvir)and Gilead Sciences Inc’sVosevi (sofosbuvir/velpatasvir/voxilaprevir) for treating chronic hepatitis C virus(HCV) infection, Dr Falk Pharma’s Jorveza (budesonide) for eosinophilic esophagitis, a rareinflammatory condition of the oesophagus,Oxervate and Brineura.
Three Conditional MA Recommendations
The CHMP last year recommended conditional marketing authorization for the following three drugs:
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- Shire PLC’s Natpar (parathyroid hormone) for patients with chronic hypoparathyroidism who cannot be adequately controlled with standard treatment with calcium and vitamin D;
- Kyowa Kirin‘s Crysvita (busorumab) for the treatment of X-linked hypophosphatemia in children and adolescents; and
- Pfizer Inc/Merck’s Bavencio (avelumab) for metastatic Merkel cell carcinoma.
Conditional marketing authorizations allow for the early approval of medicines on the basis of less complete clinical data than normally required if the medicine addresses an urgent unmet medical need. The medicines in question are subject to specific post-authorization obligations for drug developers to obtain complete data on the product.
Fifty-one extensions of indication were recommended in 2017 that could offer “new treatment opportunities for patients” – EMA
Finally, 51 extensions of indication were recommended by the CHMP in 2017. The extension of the use of a medicine that is already approved in a new therapeutic indication can offer new treatment opportunities for patients, the EMA notes. The agency highlighted Alexion Pharmaceuticals Inc’s Soliris (eculizumab) for treating refractory generalizedmyasthenia gravis in patients who areanti-acetylcholine receptor antibody-positive; and Gilead’s Truvada (emtricitabine/tenofovir disoproxil) for treating HIV-1 infectedadolescents with NRTI resistance or toxicities precluding the use of first-line agents.
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From the editors of Scrip Regulatory Affairs.