EMEA Committee Adopts 11 Positive Opinions

London (June 18–21)-The European Medicines Agency’s (EMEA) Committee for Medicinal Products for Human Use (CHMP) adopted 11 positive opinions, 3 of which are tied to similar biological medicinal products. The committee recommended granting marketing authorization for: Glaxo Group Limited’s (London) “Atriance” (nelarabine) to treat T-cell acute lymphoblastic leukaemia (T-ALL) and T-cell lymphoblastic leukaemia (T-LBL) of patients in second relapse; Medac’s (Wedel, Germany) “Gliolan” (5-aminolevulinic hydrochloride) for the visualization of malignant tissue during surgery for malignant glioma in adult patients; and Instituto Grifols S.A.’s (Barcelona, Spain) “Flebogammadif” [human normal immunoglobulin (IVIg)] for replacement therapy in immunodeficiency and for immunomodulation in immune-mediated diseases.

EMEA’s review of Atriance began last June with an active review time of 203 days. Atriance is the 40th orphan medicinal product to receive a positive opinion and the first for which an application was submitted using the Product Information Management (PIM) system. PIM enables the electronic exchange of the product information part of a marketing authorization application in the European Union to increase efficiency in product information management and exchange and to improve the quality and consistency of the published product information. EMEA’s review of Gliolan began last May with an active review time of 199 days. Gliolan is the 41st orphan medicinal product to receive a positive opinion. EMEA’s review of Flebogammadif began last September with an active review time of 177 days.

CHMP also recommended granting marketing authorization for “Rasilez,” “Enviage,” “Sprimeo,” “Tekturna,” and “Riprazo” (aliskiren) by Novartis Europharm Ltd. (London) for the treatment of essential hypertension. EMEA review began last September for Rasilez and in March 2007 for the others with an active review time of 194 for Rasilez and 77 days for the remaining four drugs.

As reported in ePT (“EMEA Recommends Epoetin Alfa Biosimilars for Approval,” June 28, 2007), The three biosimilar medicinal products that received position opinions from CHMP were: “Binocrit” (Epoetin alfa) from Sandoz GmbH(Holzkirchen, Germany), “Epoetin alfa Hexal” (Epoetin alfa), from Hexal Biotech Forschungs GmbH (London), and “Abseamed” (Epoetin alfa), from Medice Arzneimittel Pütter GMBH & Co. (Iserlohn, Germany).

During its three-day meeting, the committee also issued positive opinions for applications for extensions of indication, adding new treatment options for Glaxo Group’s previously approved Arixtra and “Quixidar” (fondaparinux sodium) 2.5 mg, to extend the indication to add treatment of acute coronary syndromes in patients with unstable angina/non-ST segment elevation myocardial infarction (UA/NSTEMI) for whom an urgent (<120 min) invasive management (PCI) is not indicated; and in patients with ST segment elevation myocardial infarction (STEMI) who are managed with thrombolytics or who initially are to receive no other form of reperfusion therapy. A positive opinion extensions of the previously approved “Zostavax” (Zoster Vaccine, Live) from Sanofi Pasteur MSD (Maidenhead, UK) to extend the indication to individuals age 50 and older was issued as well. Zostavax is currently indicated for prevention of herpes zoster and herpes zoster-related post-herpetic neuralgia (PHN) for individuals age 60 years and older.

Following a literature review describing the interaction of four known inhibitors of CYP3A4 (ketoconazole, lopinavir/ritonavir, clarithromycin, saquinavir) with midazolam, CHMP recommended to vary the product information for all protease inhibitors to contraindicate the concomitant use with oral midazolam and to provide further directions concerning coadministration with parenteral midazolam in the interaction section of the SPC. The product information for the following protease inhibitors used in the treatment of AIDS/HIVinfections has now been amended: “Agenerase,” “Crixivan,” “Prezista,” “Kaletra,” “Norvir,” “Telzir,” and “Viracept.”

CHMP completed a referral procedure under Article 29 of the Community Code on Human Medicinal Products (Directive 2001/83/EC as amended) for lansoprazole 15 and 30 mg “Gastroresistant Capsules (lansoprazole), from Teva Pharmaceutical Industries Ltd.(Petach Tikva, Israel). The committee concluded that bioequivalence with the originator medicinal product has been documented sufficiently and therefore recommended the medicinal product for approval for the treatment of gastro oesophageal reflux disease, ulcers, acidrelated dyspepsia and as an adjuvant in the eradication of Helicobacter pylori.

Finally, CHMP started several referral procedures, including for ergot-derived dopamine agonists (bromocriptine, cabergoline, dihydroergocryptine, lisuride and pergolide), a class of medicines primarily used to treat Parkinson’s disease. The referral procedure was initiated by the United Kingdom under Article 31 of the community code (Directive 2001/83/EC as amended) to reassess the balance of benefits and risks of all these products in view of the risk of fibrotic disorders and cardiac valvulopathy reported with some of these medicines. CHMP started a referral procedure for Zentiva’s (Prague) “Coxtral” gel 3% (nimesulide) because of concerns regarding equivalence with the originator medicinal product. This procedure was initiated under Article 29 of the community code (Directive 2001/83/EC as amended). And CHMP started a harmonization referral for Eli Lilly’s (Indianapolis, IN) “Gemzar” (gemcitabine) on the request of the European Commission. The procedure was initiated under Article 30 of the community code on (Directive 2001/83/EC as amended).