Ionis and AstraZeneca’s phase 3 study of Wainua (eplontersen) in ATTR-CM missed its primary endpoint, showing no statistically significant benefit when added to standard of care. This drove significant stock movement with Ionis and AstraZeneca falling nearly 24% and 6%, respectively on July 9.
Why it matters: Wainua is approved in the US and EU for hATTR-PN, but success in ATTR-CM would have been key to expanding its market potential amid competitive pressure from Alnylam’s Amvuttra and BridgeBio’s Attruby, which traded down 3% and up 15%, respectively, on July 9.
- Pfizer’s Vyndamax remains the established standard of care in ATTR-CM, while Attruby is a newer TTR stabilizer. By contrast, Wainua and Amvuttra are gene silencers, a newer class viewed as potential alternatives or add-on therapies. Today’s results raise doubts about the benefit of adding a silencer for patients already on stabilizers.
- While Alnylam’s Amvuttra should benefit from reduced competition following Wainua’s setback, BridgeBio’s Attruby stands to gain if stabilizers remain the backbone of ATTR-CM treatment.
The bottom line: For narrow-moat Ionis, we lowered our fair value estimate to USD 84 from USD 90 per share. For wide-moat Astra, we leave our fair values unchanged at GBX 13,500/USD 184.
- We view the sell-off in Ionis shares as excessive, as ATTR-CM is only one component of Ionis’ growth story. However, we also reiterate our High Morningstar Uncertainty Rating, as the setback highlights the increasingly competitive ATTR-CM field and underscores execution risk.
- Astra shares look fairly valued to us. The setback does not change our view of its late-stage drug development capabilities, and given the company’s large size, our decreased sales estimates for Wainua do not significantly change our valuation.
