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BiDil ® (isosorbide dinitrate/ hydralazine HCl). Cardiovascular and Renal Drugs Advisory Committee Gaithersburg, Maryland June 16, 2005. Introduction. Manuel Worcel, MD NitroMed. Isosorbide dinitrate (ISDN) Large and small artery dilator Venous dilator Nitric oxide donor
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BiDil® (isosorbide dinitrate/ hydralazine HCl) Cardiovascular and Renal Drugs Advisory Committee Gaithersburg, Maryland June 16, 2005
Introduction Manuel Worcel, MDNitroMed
Isosorbide dinitrate (ISDN) Large and small artery dilator Venous dilator Nitric oxide donor Hydralazine HCl (HYD) Arteriolar dilator BiDil Fixed-dose combination ISDN/HYD (20 mg and 37.5 mg, respectively, per tablet) BiDil® Mechanism of Action DV A-HeFT CSR p28;Underwood_ACC-5 O2NO H O O H ONO2 1, 4, 3, 6-dianhydro-D-glucitol-2,5-dinitrate; C6H8N2O8 NHNH2 N HCl N 1-hydrazinophthalazine monohydrochloride; C8H9ClN4
BiDil® Clinical Development in HF† DV NitroMed Briefing Book T1; V-HeFT I CSR; V-HeFT II CSR 1980 to 1985 V-HeFT I Vasodilator-Heart Failure Trial 642 men 1986 to 1991 V-HeFT II Vasodilator-Heart Failure Trial 804 men 2001 to 2004 A-HeFT African American Heart Failure Trial 1050 black men and women † V-HeFT trials used ISDN + HYD as commercial products.
1997 Medco Research receives FDA “not approvable” letter for use of BiDil to treat HF in the general population 1999 NitroMed acquires NDA file for BiDil 2001 FDA informs NitroMed that an additional clearly positive study in black patients (A-HeFT) would be basis for approval of BiDil in black patients 2004 A-HeFT trial stopped following DSMB and Steering Committee recommendations and NDA amendment submitted in December BiDil® Regulatory History DV NitroMed Briefing Book § 2.5
BiDil® Clinical Development in Black Patients With HF DV NitroMed Briefing Book pp 110, 111 • BiDil is effective: • Meaningfully reduced relative risk of mortality • Meaningfully reduced relative risk of HF hospitalization • Meaningfully improved QoL • BiDil is safe and generally well tolerated • Findings are concordant across a wide range of • Symptoms • Background medications
Proposed Indication BiDil® is indicated for the treatment of heart failure as an adjunct to standard therapy in black patients to improve survival, prolong time to hospitalization for heart failure, and improve quality of life.