CSL, seeking to stall Takeda drug, links antibody to rare disease benefits and plans global filings

CSL is coming for one of Takeda’s fastest-growing products. Phase 3 data on CSL’s garadacimab in a rare disease suggest the monoclonal antibody may have an edge over Takeda’s Takhzyro in terms of efficacy and convenience, giving the biotech a boost as it races to file global regulatory submissions this year.

In August, CSL reported the top-line success of a late-phase study that compared factor XIIa-inhibitory monoclonal antibody garadacimab to placebo in patients with hereditary angioedema (HAE), a disorder characterized by recurrent severe swelling episodes. The data drop showed garadacimab is better than placebo but offered no insights into how it holds up against the drugs used today to prevent HAE attacks.

Over the weekend, CSL revealed its results at the American Academy of Allergy Asthma & Immunology Annual Meeting. The six-month study found the 39 patients who received monthly subcutaneous doses of garadacimab had a mean attack rate reduction of 86.5% versus placebo. 

CSL showed that 61.5% of recipients of garadacimab were free from attacks during the study, while no people in the placebo cohort were free from attacks. Three-quarters (74.4%) of people in the garadacimab arm experienced a 90% or greater attack reduction versus the run-in period. Safety and tolerability look solid, with no patients dropping out as a result of adverse events. 

With the caveat that cross-trial comparisons can be unreliable, the results suggest that garadacimab may have an edge over Takhzyro, Takeda’s incumbent subcutaneous drug for preventing HAE attacks. Per its label (PDF), the mean monthly attack rate in recipients of the preferred Takhzyro starting dose was 0.26, versus 0.22 in the garadacimab study, and the reduction relative to placebo was 87%. 

Garadacimab delivered similar results, but there was daylight between the drugs in other areas. Takeda showed 67% of patients on Takhzyro had a 90% or greater reduction in HAE attacks, compared to 74.4% of participants in the garadacimab study. CSL achieved the results despite garadacimab being given half as often as Takhzyro. Patients on Takhzyro can switch to monthly dosing after six months of treatment. 

The subcutaneous products face competition from BioCryst’s oral Orladeyo, sales of which doubled last year despite it causing (PDF) a smaller reduction in attack rate than Takhzyro in its pivotal trial. Takhzyro sales grew 49% over the first nine months of its financial year, putting Takeda on track for a blockbuster year. Amid the competition, sales of CSL’s Haegarda, which is given twice a week, have flatlined (PDF). 

CSL, which plans to file for approval this year, is one of a clutch of companies targeting the HAE market. Ionis Pharmaceuticals has a subcutaneous antisense candidate in phase 3, and Intellia Therapeutics has a CRISPR-based prospect in a first-in-human study.