As with most uncommon illnesses, the marketplace for hereditary angioedema medication is small. It’s additionally comparatively crowded, served by a number of well-established merchandise and two new therapies accepted earlier this summer season. An injection from Ionis Prescribed drugs is becoming a member of the checklist, and whereas the biotech firm plans to seize new sufferers, it additionally goals to develop gross sales by getting sufferers to modify over from different merchandise. Ionis has the medical information to help this technique.
The FDA’s approval of donidalorsen, model title Dawnzera, makes this Ionis drug the primary genetic medication for hereditary angioedema, or HAE, an inherited dysfunction that results in swelling assaults all through the physique. These assaults come with out warning and may change into deadly after they shut off a affected person’s airway. The FDA’s Thursday approval of the Ionis drug covers prevention of HAE swelling assaults in sufferers age 12 and older.
An estimated 7,000 individuals within the U.S. have HAE, which stems from the inherited deficiency or dysfunction of C1 esterase. This protein regulates different proteins related to swelling and irritation. Swelling comes from uncontrolled activation of the kallikrein-kinin system. Whereas among the presently out there HAE medication block a protein known as kallikrein, Ionis goes even earlier on this pathway by going after prekallikrein (PKK), a protein that’s a precursor of kallikrein.
Dawnzera is an antisense oligonucleotide designed to bind to PKK messenger RNA, lowering manufacturing of this protein within the liver, the place it’s made. The drug, administered as a subcutaneous injection each 4 weeks or each eight weeks, is the primary and solely RNA-targeted remedy for HAE. In a 24-week Part 3 trial, dosing of the research drug each 4 weeks led to a mean 81% discount in HAE assaults in comparison with placebo. Within the one-year open-label extension research, Dawnzera decreased assaults by a mean of 94% throughout each four-week and eight-week dosing. On this research, Ionis reported that 93% of individuals achieved well-controlled illness as measured by a take a look at to evaluate HAE episodes.
Takeda Pharmaceutical’s lanadelumab, model title Takhzyro, dominates the HAE prophylaxis market. This antibody kallikrein inhibitor is accepted for sufferers age 2 and older, administered as a subcutaneous injection each two weeks, although dosing could also be prolonged to each 4 weeks for some sufferers. BioCryst Prescribed drugs markets Orladeyo, a once-daily oral small molecule kallikrein inhibitor accepted for HAE prophylaxis in sufferers age 12 and older. CSL Behring takes a special strategy with garadacimab, model title Andembry, a once-monthly antibody inhibitor of a protein known as issue XIIa that received FDA approval in June.
Acute therapies for HAE embody the C1 esterase inhibitors Ruconest, from Pharming Group, and Berinert, from CSL Behring. Takeda’s acute HAE medication are the kallikrein inhibitor Kalbitor and the bradykinin inhibitor Firazyr. The latest acute HAE remedy is KalVista Prescribed drugs’ Ekterly, an oral small molecule kallikrein inhibitor accepted by the FDA final month.
Ionis’s open-label extension research for Dawnzera included a cohort of sufferers who switched to the research drug from a special HAE prophylactic remedy. Outcomes confirmed the HAE assault charge fell by a mean 62% from prior prophylactic remedy. Moreover, 93% of individuals achieved well-controlled illness. The complete outcomes have been printed in July in The Journal of Allergy and Medical Immunology in Observe.
Talking throughout a convention name Thursday, Kyle Jenne, govt vp, chief international product technique officer for Ionis, characterised HAE prophylaxis as a “change market.” Knowledge present that about 20% of sufferers transfer between therapies, no matter whether or not it’s an injectable or oral drug. Jenne additionally cited outcomes from an Ionis-sponsored Harris Ballot of HAE sufferers exhibiting that 9 out of 10 sufferers can be desirous about making an attempt a brand new prophylactic remedy.
“There’s plenty of motivation and plenty of dissatisfaction from sufferers which are presently on current therapies,” Jenne stated. “We anticipate that over time, sufferers will probably be switching and we imagine that Dawnzera is a superb alternative for these sufferers primarily based on the profile that we’ve outlined.”
Past the efficacy information, Dawnzera presents sufferers better comfort. The drug could also be self-administered at a affected person’s house with an injection pen, Jenne stated. Having an extended dosing interval will even make a distinction for some sufferers. Whereas Ionis expects most sufferers will begin with dosing each 4 weeks, will probably be as much as a doctor to find out whether or not to increase dosing to each eight weeks.
William Blair analyst Myles Minter sees Dawnzera as a extremely aggressive within the HAE prophylaxis market. In accordance with Ionis estimates, 75% of HAE sufferers presently obtain HAE prophylactic remedy; most of them take Takeda’s Takhzyro.
“Market analysis indicating 20% of HAE sufferers change to various therapies yearly signifies an unmet want, in addition to a transparent alternative for Ionis to seize market share with Dawnzera’s differentiated, much less frequent dosing and at-home auto-injector dosing,” Minter stated in a word despatched to buyers. “Moreover, the change research performed by Ionis signifies that sufferers who strive Dawnzera favor it over their prior remedy possibility, strongly indicative of a sticky profile.”
Dawnzera’s checklist value is $57,462 per dose; about $747,000 yearly for each 4 week dosing. Ionis initiatives this product might obtain $500 million in peak gross sales. Otsuka Pharmaceutical licensed the rights to commercialize this drug in Europe in a 2023 deal.
Dawnzera is a crucial a part of Ionis’s technique to develop income from gross sales of its personal merchandise. For a lot of its historical past, Ionis partnered with bigger corporations that took duty for later-stage growth and commercialization of its oligonucleotide medication. Ionis’s high supply of business income is royalties from Spinraza, the spinal muscular atrophy drug that’s marketed by companion Biogen. Ionis reported $216 million in Spinraza royalty income in 2024.
The primary drug that Ionis commercialized by itself was Tryngolza, a remedy for the uncommon metabolic dysfunction familial chylomicronemia syndrome that the FDA accepted in late 2024. For the primary half of 2025, Ionis reported $25.5 million in Tryngolza income.
Photograph by Ionis Prescribed drugs
