First-of-its-kind therapy Dawnzera wins FDA approval for HAE
Formerly donidalorsen, the treatment should be available soon in the US
The U.S. Food and Drug Administration (FDA) has approved donidalorsen — to be marketed Dawnzera — as a prophylactic treatment for swelling attacks in adults and adolescents, ages 12 and older, with hereditary angioedema (HAE).
With this decision, Dawnzera has become the first and only RNA-targeted therapy approved for HAE. Its developer, Ionis Pharmaceuticals, expects the therapy to become available in the U.S. in the coming days. An application for approval has been accepted for review in Europe, where Otsuka Pharmaceutical holds the rights to it. An application in Canada is being prepared by Theratechnologies.
“Dawnzera represents a significant advance for people living with HAE who need improved treatment options,” Brett P. Monia, PhD, CEO of Ionis, said in a company press release. “To the patients, families, advocacy partners, and investigators who helped make this moment a reality, we express our deepest gratitude.”
To help patients get started on treatment, the company is providing a support service program called Ionis Every Step. As part of it, patients and healthcare providers may access to a range of support and resources, including a dedicated patient education manager, access to the Dawnzera Direct digital companion, insurance assistance, and more.
How does Dawnzera work in HAE?
The U.S. approval was welcomed by the HAE community.
“As the first FDA-approved RNA-targeted therapy for HAE, Dawnzera represents a welcome advance in therapeutic options for preventing attacks. Today’s approval gives people living with HAE and their physicians another important choice for aligning treatment with individual needs,” said Anthony J. Castaldo, CEO and chairman of the board at the U.S. Hereditary Angioedema Association (HAEA) and Hereditary Angioedema International (HAEi).
In HAE, recurrent swelling attacks, which can affect different parts of the body are result from genetic mutations that lead to too much of the signaling molecule bradykinin being produced, causing blood vessels to become more permeable and leak fluid into nearby tissues.
Dawnzera is an antisense oligonucleotide, or a short, lab-made molecule made up of genetic material. It’s designed to reduce the production of prekallikrein, a precursor of kallikrein, an enzyme needed for bradykinin production. By doing this, Dawnzera should keep bradykinin from rising too high, thereby preventing or reducing swelling attack frequency.
As detailed in its prescribing information, Dawnzera is given by an injection under the skin, or subcutaneously, at a recommended dosage of 80 mg every four weeks. A more extended dosing interval of once every eight weeks may also be considered in some cases. The therapy comes in a single-dose autoinjector and is meant to be self-administered by patients or given by caregivers after proper training.
“With strong and durable efficacy, convenient administration and the longest dosing option available, we believe Dawnzera will be the prophylactic treatment of choice for many people living with HAE,” Monia said.
Results against HAE attacks
The FDA’s decision was mainly supported by data from the Phase 3 OASIS-HAE clinical trial (NCT05139810), which included 90 adults and adolescents, ages 12 and older, with HAE types 1 or 2, who were having recurrent swelling attacks. The participants were randomly assigned to receive Dawnzera at 80 mg every four or eight weeks, or a matching placebo, for about six months.
After that time, Dawnzera reduced monthly HAE attack rates by 81% when given once monthly and by 55% given every other month over a placebo. Mean HAE attack rates dropped by 87% with monthly treatment relative to a placebo from the second dose to the study’s end. In that same period, monthly Dawnzera lowered the rate of moderate to severe attacks and of those that required on-demand treatment by about 90%.
Similar benefits were seen in OASISplus (NCT05392114), an open-label extension study that enrolled patients who’d completed OASIS-HAE as well as some who’d never received Dawnzera and had been on other prophylactic therapies. Reductions in attack rates seen in OASIS-HAE were sustained after a year in OASISplus, with mean attack rates dropping by more than 90% in those receiving Dawnzera every four or eight weeks.
HAE attack rates also dropped by a mean of 62% after about four months of monthly treatment with Dawnzera in those patients who switched from other approved HAE preventive therapies to Dawnzera in the extension study. Most of these patients said they preferred Dawnzera over their previous therapy, considering it better at controlling HAE, took less time to administer, and led to fewer injection site pain or reactions.
“People living with HAE manage this condition for all their lives, and many continue to face unpredictable, painful and dangerous breakthrough attacks even with current treatments,” said Marc Riedl, MD, clinical director of the U.S. HAEA Angioedema Center and investigator in OASIS-HAE and OASISplus. “Dawnzera is positioned to help meet patient needs, providing substantial and sustained reduction of HAE attacks, continued improvement over time and reduced burden of treatment.”
Dawnzera’s safety profile has also been favorable across different studies. The most common side effects reported include injection site reactions, upper respiratory tract infection, urinary tract infection, and abdominal discomfort.
About the Author
