AZ, Ionis hit by unexpected Wainua trial failure
Shares in AstraZeneca were trading down more than 8% this morning after it revealed that its transthyretin amyloidosis (ATTR) therapy, Wainua, missed the mark in a trial in patients with cardiomyopathy (CM).
Ionis-partnered Wainua (eplontersen) was unable to show an improvement in cardiovascular (CV) mortality and recurrent CV clinical events up to 140 weeks compared with placebo when added to standard care in the phase 3 CARDIO-TTRansform study, denting the drug's commercial prospects.
There are two main forms of ATTR; one that leads to cardiomyopathy (ATTR-CM), which impacts the heart, and another that causes polyneuropathy (ATTR-PN), which damages nerves in the hands, feet, and arms.
Wainua – a gene-silencing drug given as a once-monthly injection – is already approved for the ATTR-PN form, bringing in more than $210 million in sales last year and earning Ionis around $49 million in royalty revenue.
However, unlocking the ATTR-CM market – with around 300,000 to 500,000 patients worldwide versus less than 50,000 with ATTR-PN – is seen as crucial to meeting peak sales projections for the drug. Nasdaq-listed Ionis' share price was also hit, trading down more than 17% pre-market at the time of writing.
A report in the Financial Times suggested that peak sales for the drug will now be in the region of $4 billion, still impressive but short of the $6.5 billion forecast for Wainua before the CARDIO-TTRansform failure.
Current approved treatments for ATTR-CM – Pfizer's Vyndamax (tafamidis), BridgeBio Pharma's Attruby (acoramidis), and Alnylam's Amvuttra (vutrisiran) – are all at or near blockbuster sales status, with Pfizer's market-leading drug pulling in almost $6.4 billion.
AZ's head of biopharmaceuticals R&D, Sharon Barr, said that while CARDIO-TTRansform did not meet its primary objective, "we believe the results support greater scientific understanding of treatment approaches for the hundreds of thousands of patients worldwide suffering from this progressive and often fatal condition."
There were some glimmers of efficacy in the data. For instance, a subgroup of patients receiving monotherapy with Wainua showed a "nominally significant" improvement over placebo on the composite endpoint, but AZ was relying on a solid benefit as an add-on therapy to give Wainua a competitive position in the market.
An analysis of the reasons for the disappointing result will come when the results of CARDIO-TTRansform are reported at the European Society of Cardiology (ESC) annual congress in Munich, Germany, next month.
Analysts at Jefferies said that the result should not affect AZ's ambitious target of growing its revenues to $80 billion by 2030 from $58.7 billion last year.
The readout was one of three that AZ hoped would deliver big results this year, with eyes now turning to the SERENA-4 trial of oral SERD camizestrant in an all-comer HR-positive breast cancer population and the AVANZAR study of TROP2-targeting Datroway (datopotamab deruxtecan) as a first-line therapy for advanced non-small cell lung cancer (NSCLC).
