ISTH 2024 – Takeda's marker for Genmab and Sanofi
If the rare immune-mediated bleeding disorder immune thrombocytopenia (ITP) represents a new use for anti-CD38 therapy then Takeda’s mezagitamab just gave Johnson & Johnson/Genmab’s Darzalex and Sanofi’s Sarclisa something to shoot for. In a small phase 2 trial all three mezagitamab doses appear to have shown platelet increases above 50,000/μl, seen as indicative of a response, that were fast, and persisted to eight weeks (when dosing ended) and 16 weeks (including a further eight weeks’ follow-up). Dose dependence across several platelet response measures could broadly be seen, with 600mg doing best, and all numerically beating a placebo group, Takeda’s late-breaking presentation at the International Society on Thrombosis and Haemostasis this weekend revealed. Such numbers might be relevant in light of Darzalex’s ITP study, Dart, which should yield data imminently. However, it’s not apparent that ITP is a focus for either the makers of Darzalex – a multiple myeloma behemoth – or its disappointing CD38 rival Sarclisa, from Sanofi; both their ITP trials are academic sponsored. For its part Takeda, which recognised the Darzalex threat by discontinuing mezagitamab work in multiple myeloma, plans to start a global phase 3 ITP trial in the second half.
Phase 2 controlled data for mezagitamab vs placebo
| Placebo | Mezagitamab 100mg | Mezagitamab 300mg | Mezagitamab 600mg | |
|---|---|---|---|---|
| Number of patients | 13 | 9 | 8 | 11 |
| Mean increase in platelet count at 8wk* | 0/μl | 55,000/μl | 65,000/μl | 90,000/μl |
| Mean increase in platelet count at 16wk* | 5,000/μl | 90,000/μl | 60,000/μl | 70,000/μl |
| Platelet response ≥50,000/μl, and ≥20,000/μl on ≥2 visits | 23.1% | 66.7% | 62.5% | 90.9% |
| Complete platelet response, ≥100,000/μl on ≥2 visits | 0.0% | 55.6% | 50.0% | 81.8% |
Note: *number read from graph. Source: ISTH.
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