Ionis Bets patients will switch to their new first class of drugs in a crowded market for rare diseases
Like most rare diseases, the market for hereditary angioedema is also small. It is also relatively crowded, with several recognized products and two new treatment services approved earlier this summer. Ionis Pharmaceuticals injections are being added to the list, and BioTech plans to capture new patients, it is also aiming to increase sales by allowing patients to switch from other products. Ionis has clinical data that supports this strategy.
FDA approval of Donidalorsen, the brand Dawnzera, makes this Ionis drug the first genetic medicine for hereditary angioedema or HAE, or HAE is a hereditary disease that causes swelling throughout the body to attack. These attacks have no warning and can be fatal when they close the patient's airways. FDA’s approval of IONIS drugs on Thursday covered HAE swelling attacks in patients aged 12 and over.
An estimated 7,000 people in the United States have HAE, which is caused by genetic defects or dysfunction of C1 esterase. This protein regulates other proteins associated with swelling and inflammation. Swelling comes from uncontrolled activation of the Kallikrein-Kinin system. While some of the currently available HAE drugs block a protein called Kallikrein, Ionis was able to follow Prepkallikrein (PKK), even in the early stages of this pathway, a protein that is a precursor to Kallikrein.
Dawnzera is an antisense oligonucleotide designed to bind to PKK Messenger RNA, thereby reducing the production of this protein in the liver. The drug is administered as a subcutaneous injection every four weeks or eight weeks, and is the first and only targeted RNA-targeted therapy for HAE. In a 24-week phase 3 trial, the average reduction in HAE challenge was 81% lower than placebo every four weeks. In a one-year open-label extension study, Dawnzera suffered an average of 94% reduction in attacks over four- and eight-week doses. In this study, Ionis reported that 93% of participants achieved good disease control by testing to assess HAE episodes.
Takeda Pharmaceutical's Lanadelumab, brand Takhzyro's Lanadelumab dominates the HAE prevention market. The antibody kallikrein inhibitor has been approved for patients aged 2 and 2 years old as subcutaneous injection every two weeks, although some patients may be extended every four weeks. Biocryst Pharmaceuticals Market Orladeyo is a once-daily oral small molecule Kallikrein inhibitor that approved HAE prevention in patients aged 12 and 12 years and older. CSL Behring has taken a different approach with Garadacimab, brand and Embry, a former antibody inhibitor of protein XIIA, which won FDA approval in June.
Acute treatment of HAE included the C1 esterase inhibitor ruconest from the drug group and Berinert from CSL Behring. Takeda's acute HAE drugs are Kallikrein inhibitor Kalbitor and Bradykinin inhibitor Firazyr. The latest acute HAE therapy is Ekterly from Kalvista Pharmaceuticals, an oral small molecule Kallikrein inhibitor approved by the FDA last month.
Ionis' open label extended study of Dawnzera includes a population of patients who have converted from different HAE prophylactic treatments to study drugs. The results show that the HAE challenge rate decreased by an average of 62% compared with previous prophylactic treatments. In addition, 93% of participants obtained well-controlled diseases. All results were published in the Journal of Allergy and Clinical Immunology in July.
Kyle Jenne, executive vice president and chief global product strategy officer at Ionis, spoke on Thursday’s conference call, describing HAE PREPHAXIS as a “switch market.” Data show that approximately 20% of patients move between treatments, whether injectable or oral medications. Jenny also cites results from HAE patients sponsored by the IONIS-sponsored Harris poll, indicating that nine out of 10 patients were interested in trying a new preventive treatment.
“There is a lot of motivation and a lot of dissatisfaction with patients currently being treated,” Jenny said. “We hope that patients will switch over time and we believe Dawnzera is an excellent choice for these patients based on the profile we outlined.”
In addition to efficacy data, Dawnzera also provides greater convenience for patients. Jenny said the drug can be self-managed at the patient's home with an injection pen. Having longer dosing intervals can also have an impact on some patients. While Ionis expects most patients to start with every four weeks of administration, it is important to determine whether the dosage will be extended to every eight weeks.
William Blair analyst Myles Minter believes Dawnzera is extremely competitive in the prevention market. According to Ionis estimates, 75% of HAE patients currently receive prophylactic treatment. Most of them hold Takhro from Takeda.
“Market studies show that 20% of HAE patients switch to alternative treatments each year, suggesting the need for differentiated, less frequent doses and obvious opportunities to capture market share with Dawnzera,” Minter said in a note sent to investors. “In addition, switching studies conducted by Ionis show that patients who try Dawnzera prefer it more than previous treatment options, which strongly suggests a sticky profile.”
Dawnzera is priced at $57,462 per dose; the dose is about $747,000 per year every four weeks. The Ionis Project product can achieve peak sales of $500 million. Otsuka Pharmaceutical has gained the right to commercialize the drug in Europe in its 2023 deal.
Dawnzera is an important part of Ionis' strategy to grow revenue from selling its own products. For much of its history, Ionis has worked with large companies responsible for the late development and commercialization of its oligonucleotide drugs. Ionis' highest source of commercial income is the royalties of Spinraza, a spinal muscle atrophy sold by partner Biogen. Ionis reported $216 million in Spinraza royalty revenue in 2024.
The first drug Ionis commercialized alone is Tryngolza, a treatment for rare metabolic familial chylopathy syndrome approved by the FDA at the end of 2024. In the first half of 2025, Ionis reported $25.5 million in Tryngolza Revenue.
Image by Ionis Pharmaceuticals
