Ionis looks average in amyloidosis

 In June Ionis said that its hereditary transthyretin-mediated amyloid polyneuropathy project eplontersen had hit in phase 3; today it gave the magnitude of transthyretin knockdown, and though it is statistically significant the effect is similar to that seen with the three approved drugs. More interestingly, it does not look as good as that seen with Intellia’s much earlier-stage rival project, NTLA-2001. Eplontersen’s safety looks clean, putting it ahead of Ionis’s approved product Tegsedi, but so does NTLA-2001’s, so Intellia could still be a threat. Ionis and its partner Astrazeneca intend to file an NDA by the end of 2022; Stifel believes eplontersen could seize a 30% share within the silencer market in the long term. This is currently split roughly 90%-10% between Alnylam’s Onpattro and Tegsedi.

Cross-trial comparison of therapies for hereditary transthyretin amyloid polyneuropathy
Drug	Description	Trial	Time point	Pbo-adj chg on mNIS+7	Pbo-adj chg on Norfolk QoL-DN	Mean chg in serum TTR
Onpattro (Alnylam)	IV TTR RNAi therapeutic, given every 3wk	Ph3 Apollo	18mth	-34	-21	84%
Amvuttra (Alnylam)	SC TTR RNAi therapeutic, given every 3mth	Ph3 Helios-A	9mth	-17	-16	83%
Tegsedi (Ionis)	SC TTR antisense, given once weekly	Ph2/3 (NCT01737398)	15mth	-20	-12	74%
Eplontersen (Ionis/AZ)	SC TTR antisense, given once monthly	Ph3 Neuro- TTRansform	8mth*	Hit  (p<0.0001)	Hit  (p<0.0001)	82% (p<0.0001)
NTLA-2001 (Intellia)	IV in vivo Crispr-edited project	Ph1 (NCT04601051)	6mth	Not given	Not given	93%**
TTR=transthyretin. mNIS+7=modified neuropathy impairment score +7. Norfolk QoL-DN=Norfolk quality of life questionnaire-diabetic neuropathy. *Interim data; final readout at 66wk. All eplontersen p values are comparisons with historical control. **With 1mg/kg dose. Source: drug labels, company releases. https://www.evaluate.com/vantage/articles/news/trial-results-snippets/ionis-looks-average-amyloidosis