CSL has announced positive results from its Phase 3 VANGUARD trial evaluating garadacimab, a once-monthly subcutaneous therapy for hereditary angioedema (HAE). The trial's success paves the way for regulatory submissions and positions CSL to challenge Takeda's market-leading Takhzyro. The full data, presented at the American Academy of Allergy, Asthma & Immunology (AAAAI) congress, indicates that garadacimab offers comparable efficacy with a potentially more convenient administration schedule.
HAE is a rare genetic condition affecting approximately 1 in 10,000 to 1 in 50,000 individuals globally. It is characterized by unpredictable, recurring episodes of severe swelling in various body parts, which can be life-threatening if the airways are affected.
VANGUARD Trial Results
The VANGUARD trial demonstrated that garadacimab significantly reduced the average number of monthly HAE attacks by 86.5% compared to placebo. Specifically, the mean monthly attack rate was reduced to 0.22 with garadacimab, compared to an average of around two attacks per month at enrollment. A significant 61.5% of patients receiving garadacimab were attack-free during the six-month study period, while no patients in the placebo group experienced the same outcome. The therapy was also well-tolerated, with no dropouts reported due to adverse events.
Comparison with Existing Therapies
The results hold promise when compared to Takeda's Takhzyro (lanadelumab), a plasma kallikrein inhibitor administered via subcutaneous injection every two weeks, though the frequency can be reduced to once a month for patients with well-controlled symptoms over six months. In its pivotal efficacy study, Takhzyro achieved an 87% reduction in HAE attacks over six months compared to placebo, with a mean monthly attack rate of 0.26 at six months.
While direct comparisons between trials with differing designs are challenging, the data suggests that garadacimab's potential market success will depend on its less frequent dosing schedule and other factors, such as pricing strategies. Other competitors include BioCryst Pharma’s Orladeyo (berotralstat), an oral medication taken once daily, targeting HAE patients with fewer attacks or those with venous access challenges.
CSL's HAE Portfolio
If approved, garadacimab will complement CSL's existing HAE portfolio, which includes Berinert (administered intravenously for acute HAE attacks) and Haegarda (a twice-weekly subcutaneous injection for HAE prevention). However, sales of Haegarda and Berinert have seen limited growth since the introduction of rival therapies, with increases of only 1% to $224 million and 4% to $131 million, respectively, in the first six months of CSL’s current fiscal year.
