Date: 2012-03-06
Type of information:
phase: 2
Announcement: results
Company: Viropharma (USA) Halozyme Therapeutics (USA)
Product: Cinryze® in combination with Halozyme\'s Enhanze™ technology
Action
mechanism: Cinryze® is a highly purified, pasteurized and nanofiltered plasma-derived C1 esterase inhibitor.
Halozyme\'s Enhanze™ technology, a proprietary drug delivery platform using recombinant human hyaluronidase enzyme (rHuPH20) facilitates the absorption and dispersion of drugs or fluids that are injected under the skin. Recombinant HuPH20 transiently generates channels in subcutaneous tissues to increase the absorption and spread of injected drugs.
Disease: hereditary angioedema
Therapeutic area: Rare diseases - Genetic diseases
Country:
Trial details: This open-label, multiple-dose Phase 2 study was conducted in 12 subjects with HAE who previously participated in the ViroPharma trial evaluating the pharmacokinetics of subcutaneous injections of Cinryze® when given alone relative to intravenous infusion. Qualified subjects participated in a single 18-day study period, followed by a 30-day post-treatment follow-up. A 1000U or 2000U dose of Cinryze® in combination with rHuPH20 was administered as a single subcutaneous injection, twice weekly, allowing within-subject comparison across the different methods of administration. Plasma C1 INH functional activity was assessed by chromogenic assay and plasma C1 inhibitor antigenic concentration and C4 complement levels were assessed by ELISA.
Latest
news: ViroPharma and Halozyme Therapeutics announced the presentation of positive data from ViroPharma \'s Phase 2 subcutaneous trial of Cinryze® (C1 esterase inhibitor [human]) in combination with Halozyme\'s Enhanze™ technology in patients with hereditary angioedema (HAE), a rare, debilitating and potentially fatal genetic disease. The presentation occurred as part of the late-breaker session at the 2012 annual meeting of the American Academy of Allergy Asthma & Immunology (AAAAI), held March 2 to 6, 2012 in Orlando , Fla.
According to the presenters, these data demonstrate that subcutaneous co-administration of Cinryze® with rHuPH20 was easy to administer, well tolerated and resulted in sustained physiologically relevant C1 INH functional concentrations. The presenters concluded that this innovative combination administered subcutaneously as a single injection will be further evaluated for the prevention of HAE attacks.
Cinryze® is approved in the United States as intravenous (IV) administration for routine prophylaxis against angioedema attacks in adolescent and adult patients with HAE, and in Europe for routine prevention, pre-procedure prevention and acute treatment of angioedema attacks in adolescent and adult patients with HAE.
In poster #5208 entitled, \'Safety, Pharmacokinetics (PK), and Pharmacodynamics (PD) of Subcutaneous (SC) Cinryze® (C1 inhibitor (C1 INH) with Recombinant Human Hyaluronidase (rHuPH20) in Subjects with Hereditary Angioedema (HAE),\' Jennifer Schranz , M.D., ViroPharma \'s vice president of clinical research, and colleagues discussed key study results.
• Cinryze® with rHuPH20 was well tolerated with no serious adverse events (SAEs), and no adverse events (AEs) led to study drug discontinuation:
• No subjects experienced an HAE attack during the study;
• Mild to moderate injection site reactions were the most frequently reported AEs.
• Cinryze with rHuPH20 delivered physiologically relevant C1 INH functional concentrations
o Cinryze 2000U with rHuPH20 resulted in mean C1 INH functional concentrations greater than or equal to 0.4U/mL for 92 percent of the 72 hour post dosing period as compared to 73 percent for 1000U IV.
Addition of rHuPH20 to Cinryze® 2000U resulted in a statistically significant increase in bioavailability of C1 INH antigen relative to Cinryze® 2000U alone;
The addition of rHuPH20 to Cinryze® resulted in a dose proportional increase of C1 INH function for Cmax, Cavg, and AUCtau over the 1000 to 2000U dose range;
No C1 INH antibodies were detected during the 30 day post treatment follow up after the last dose of Cinryze®.
The results of this study support further clinical development of the combination, and move closer to potentially enabling prevention-minded patients living with HAE to self administer the drug subcutaneously with a single injection per dose.
