Breakthrough Clinical Results

Astria Therapeutics announced that it will present safety and efficacy data from Phase 1a and 1b/2 clinical trials of navenibart, a monoclonal antibody inhibitor of plasma kallikrein, at the 14th C1 Inhibitor Deficiency and Angioedema Workshop in Budapest. Dr. Marc A. Riedl will present the data, focusing on safety, pharmacokinetics, and pharmacodynamics in patients with hereditary angioedema (HAE). Navenibart is Astria's lead program for the treatment of HAE, and this presentation highlights its progress in clinical development.

Incidence and Prevalence

Latest Estimates of Hereditary Angioedema Incidence and Prevalence

Based on PubMed data, Hereditary Angioedema (HAE) is recognized as a rare disease with limited global epidemiological data. It is characterized as the most frequent among hereditary deficiencies of the complement system.

In France specifically, 250 cases have been identified, providing one of the few concrete prevalence figures available. This limited data point gives some indication of the rarity of the condition in a single national population.

Despite its rarity, HAE represents a severe disease with significant mortality, being fatal in 15-20% of patients before they reach 40 years of age. This underscores the critical importance of proper diagnosis and management.

While specific global statistics are sparse, there is some evidence suggesting that hereditary angioneurotic edema is probably a more frequent disease than previously presumed. This indicates potential underdiagnosis or misdiagnosis in various populations.

It's worth noting the contrast between HAE and related conditions - while HAE remains rare, approximately 10 to 25% of the population experience urticaria during a lifetime, highlighting the relative rarity of HAE compared to other angioedema-related conditions.

The limited epidemiological data available points to the need for more comprehensive global studies to better understand the true incidence and prevalence of this potentially life-threatening condition.

Economic Burden

Study Design Parameters

Study Design Parameters and Endpoints in Key Hereditary Angioedema Trials

Study 1 (Danish Registry Analysis)

• Design Parameters:

• Compared HAE patients with control group of Quincke's edema (QE) or bee/wasp allergy patients

• Examined hospital contacts and diagnoses before HAE diagnosis was established

• Endpoints:

• Found QE was most common diagnosis code before specific HAE diagnosis

• HAE patients had hospital visits once every other year before diagnosis, and once during year before diagnosis

• Many patients contacted dermatologists in year before diagnosis

• Unable to identify specific "digital fingerprint" distinguishing HAE patients from control group

Study 2 (FFP Research)

• Design Parameters:

• Objective: Determine if Fresh Frozen Plasma (FFP) can exacerbate symptoms or precipitate HAE attacks

• Methods: PubMed and OVID search with keywords (hereditary angioedema, angioedema and fresh frozen plasma, angioedema and FFP, hereditary angioneurotic edema)

• English-language articles searched from 1966 to present

• Review of medical records of HAE patients who received FFP since 1990

• Endpoints:

• No evidence that FFP exacerbated symptoms or precipitated attacks

• Found FFP effective as prophylactic agent before surgery and for acute HAE attacks

Study 3 (Acquired Angioneurotic Edema)

• Design Parameters:

• Investigated clinical and biochemical features in nine patients with acquired angioneurotic edema (AAE)

• Endpoints:

• Four patients had type I AAE with accelerated metabolism of C1Inh associated with hematology disease

• Low C4, C1q and C1Inh plasma levels in type I patients

• Four patients had type II AAE associated with autoantibody to C1Inh

• One patient had AAE induced by oral contraceptives

Study 4 (Prodrome Literature Review)

• Design Parameters:

• Literature review of English language journal articles using search terms: hereditary angioedema, HAE, angioneurotic edema, prodrome, signs, and symptoms

• Nineteen original articles reviewed

• Endpoints:

• Found significant variability in expression, manifestation, prevalence, timing, and predictive reliability of prodromes

• No evidence found regarding sensitivity and specificity for accurately predicting attacks

Study 5 (Pharmacogenetic Predictors)

• Design Parameters:

• Enrolled 111 subjects randomized into two groups: patients with angioedema as side effect to enalapril, and control group without adverse reaction

• All patients underwent pharmacogenetic testing

• Endpoints:

• Found association between angioneurotic edema and genotypes AA rs2306283 (SLCO1B1), TT rs4459610 (ACE), and CC rs1799722 (BDKRB2)

Study 6 (Danazol Prophylaxis)

• Design Parameters:

• Evaluated efficacy of short-term danazol prophylaxis in HAE patients undergoing maxillofacial or dental procedures

• 12 patients with history of edema after dental procedures received danazol (600 mg/d) 4 days pre-op and 4 days post-op

• Serum levels of complement components measured in 6 patients

• Endpoints:

• None of the 12 patients developed angioneurotic edema

• Serum complement components decreased after surgery, returned to normal within 24 hours

Drug used in other indications

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