As medicine evolves, even smaller therapeutic areas are impacted by scientific breakthroughs and novel technologies, leading to an eruption of new therapies. Hereditary angioedema (HAE), a rare genetic disorder affecting 1 in 50,000 people worldwide, is the latest indication to reap the benefits of several new market entrants.
Due to a deficiency of the C1 inhibitor protein, HAE patients experience recurrent episodes of severe swelling in various parts of the body, most commonly the face, throat, limbs, and intestinal tract. Individuals with HAE are subject to painful, unpredictable episodes of sudden-onset angioedema, which typically occur every few weeks. Before the advent of targeted therapies, HAE patients had a high mortality rate of approximately 25%, due to obstruction of the airway during acute attacks.
For years, the standard of care for HAE has included genetic testing to diagnose and categorize the disorder into type I vs. type II. Treatment consists of short-term management for acute attacks and various prophylactic therapies to reduce the number of attacks.
Legacy prophylactic treatments include CSL Behring’s Haegarda, which contains a C1 esterase inhibitor (C1-INH) protein, and two plasma kallikrein inhibitor (PKI) therapies, BioCryst’s Orladeyo and Takedo’s Takhzyro. Legacy acute treatments include CSL Behring’s Berinert and Pharming’s Ruconest, both C1-INH drugs.
Novel Treatments with New MoAs
In the past few months, several new treatments have upended the HAE landscape, providing more options for prophylaxis than ever before. This group also includes the first oral drug for acute therapy.
In June 2025, CSL Behring’s Andembry gained FDA approval, representing a new mechanism of action (MoA) for this condition. Andembry is a first-in-class monoclonal antibody that inhibits Factor XII (FXIIa), the plasma protein that first launches the contact activation pathway that ultimately leads to HAE attacks. This once-monthly shot reduces the frequency and severity of attacks requiring on-demand treatment.
In July, Kalvista Pharmaceuticals’ Ekterly also gained FDA approval, becoming the first on-demand oral drug indicated to treat HAE attacks. If the first dose does not provide symptom relief, patients can take a second dose within three hours, halving the wait time necessary for Ekterly’s competitors, which are all self-injectable intravenous or subcutaneous products.
In August 2025, Ionis’s Dawnzera became the first RNA-targeted prophylactic medicine for HAE, representing another new MoA for this disease. Dawnzera, an antisense oligonucleotide, blocks the body’s synthesis of prekallikrein (PKK) protein, which causes swelling and fluid leakage in HAE attacks. Ionis touts Dawnzera as having the longest dosing option (four or eight weeks) of current prophylactic treatments for HAE.
On the horizon are two additional therapies. Pharvaris is in the midst of two Phase 3 studies for deucrictibant, an oral bradykinin B2 receptor antagonist developed both for long-term, prophylactic use and on-demand treatment for HAE attacks. Another manufacturer, Intellia Therapeutics, is currently in Phase III trials for its gene-editing medicine, a potentially curative therapy known as NTLA-2002, which is expected to launch in 2027.
Competitive Strategies for New Market Entrants
In just a short period of time, this indication has become a competitive market, with a profusion of treatment options available for both prophylaxis and acute attacks. Payers appreciate having these options available, as many patients with HAE routinely discontinue and/or switch therapies due to adverse reactions, insufficient efficacy, and other reasons.
As both prophylactic and acute-attack therapies now include options for both oral and injectable treatments, patients will be able to choose their preferred route of administration (RoA). According to payer feedback collected via MMIT’s Message Monitor, many payers anticipate that patients will make the switch from subcutaneous and intravenous therapies to an easier, more convenient oral therapy.
More competition also means better contracting for payers, especially for brands with similar MoAs. Manufacturers of new market entrants should highlight their product’s key clinical differentiators, whether that be a novel MoA, simplified dosing regimen, faster onset time, or the route of administration.
Manufacturers should also make sure that payers compare apples to apples, especially when it comes to pricing and cost benefit analysis. Even seemingly minor differences in dosing frequency, packaging, and storage can impact payers’ perception of a brand’s relative cost efficacy.
Payers will also be interested in how various types of prophylactic and acute therapies impact the overall annual cost of a patient with HAE. For example, is the high cost of a new prophylactic therapy offset by the patient’s avoidance of acute attacks in the future?
Access Strategies for Legacy Brands
As with any therapeutic area flooded with new competitors, manufacturers of older HAE brands should monitor market developments and act accordingly. If a manufacturer hasn’t recently engaged with payers, they should consider a targeted re-engagement campaign to reshare relevant clinical data that might differentiate their brand from these new entrants.
This engagement can be a simple reminder of a brand’s value propositions, or it can be a far more complex enterprise, such as running new trials to establish clinical differentiation. Market research to capture payer and IDN perspectives on each brand and its competitors might also be useful. For example, MMIT’s Message Monitor solution is particularly useful in determining how payers are responding to disruptive market events, which then helps legacy manufacturers create payer and prescriber counter-messaging.
Ideally, manufacturers of older HAE drugs should also consider developing new oral versions of their therapies to counteract market entrants with a new route of administration. They can also share real-world data and positive patient feedback about their therapy, such as patient-reported outcomes data about the ease of auto-injections.
To summarize, patients with rare diseases like HAE are benefitting from the development of more novel treatments, including brand new MoAs. With this competition comes a flurry of payer contracting, which means that manufacturers must work to understand their competitors’ messaging and differentiators in order to distinguish their brand.
For HAE, the high number of launches today means that all manufacturers in this space—from those that launched brands years ago to those that will not launch a brand for years—must develop a competitive market access strategy. Manufacturers of HAE therapies still in development should consider launching payer messaging much earlier than usual, as they will want payers to keep their products in mind during this period of heavy activity.
For insights into competitor strategies and your brand’s message performance, learn more about MMIT’s Message Monitor solution.
