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Relationship Between Drug Exposure and Clinical Response Observed in the Phase 1b Study of DX-2930 in Subjects with Hereditary Angioedema
Monday, March 7, 2016
South Exhibit Hall H (Convention Center)
Joshua S. Jacobs, MD, Paula J. Busse, MD FAAAAI, Aleena Banerji, MD, Mustafa Shennak, William R. Lumry, MD FAAAAI, Mark A. Davis-Lorton, MD FAAAAI, H. James Wedner, MD FAAAAI, James W. Baker, MD FAAAAI, Jonathan A. Bernstein, MD FAAAAI, Richard F. Lockey, MD FAAAAI, H. Henry Li, MD PhD, Timothy J. Craig, Marco Cicardi, Marc A. Riedl, MD MS, Ahmad Al-Ghazawi, Carolyn Soo, Ryan Iarrobino, Daniel Sexton, Christopher TenHoor, Ryan Faucette, Joseph C. Biedenkapp, Yung H. Chyung, Burt Adelman
Rationale: DX-2930 is a human monoclonal antibody inhibitor of plasma kallikrein in development for the prevention of hereditary angioedema (HAE) attacks. Data from the phase 1b study of DX-2930 in HAE subjects was analyzed to characterize the relationship between drug exposure and clinical response.

Methods: Subjects with Type I/II HAE were randomized to receive 2 subcutaneous doses of DX-2930 on Days 1 and 15 in dose groups of 30, 100, 300 or 400 mg (n=4, 4, 5, 11) or placebo (n=13). A post-hoc modified efficacy analysis was conducted that excluded 1 subject who received only one dose of DX-2930 and 1 subject who did not have HAE Type 1/2. The incidence of HAE attacks was evaluated in relation to drug exposure over time in subjects receiving the full dose regimen of DX-2930.

Results: In the modified efficacy analysis, from Day 8 to 50 in comparison to placebo, the 300 and 400 mg DX-2930 groups had a 100% (P<0.0001) and 95% (P=0.0022) reduction in attacks, respectively. Placebo-treated subjects reported HAE attacks throughout the study (9 subjects, 65 HAE attacks). In the 300 and 400 mg dose groups, HAE attacks were reported prior to or just after initial dosing. When drug levels were high (Day 8 to 50), all but 1 subject was attack free. As drug levels waned, attacks re-emerged. No safety signal correlating with drug exposure was observed.

Conclusions: HAE attacks substantially decreased or were eliminated during periods of notable drug exposure.