Connect Biopharma (NASDAQ:CNTB) discussed phase 2 results for rademikibart in acute chronic obstructive pulmonary disease, or COPD, during an H.C. Wainwright-hosted call featuring Surya P. Bhatt, Professor of Medicine in the Pulmonary Division at the University of Alabama at Birmingham.
Bhatt said acute COPD exacerbations remain a major unmet medical need, with treatment practices largely unchanged for decades. Standard care generally consists of corticosteroids, antibiotics and bronchodilators, while more severe cases may require hospitalization, oxygen or non-invasive ventilation.
“The exacerbation treatment paradigm has not changed in almost five decades now,” Bhatt said. “It has always been steroids, either by mouth or IV.”
High Risk Following COPD Exacerbations
Bhatt described COPD as a condition generally characterized by fixed or partially irreversible airflow obstruction, distinguishing it from asthma, where airway obstruction is more reversible and responsive to bronchodilators. COPD commonly develops later in life and cigarette smoking remains its primary risk factor, though the disease also occurs in non-smokers.
He said patients recovering from an exacerbation can remain symptomatic for weeks and face elevated risk of another event soon after discharge. According to Bhatt, a single moderate exacerbation increases the risk of another exacerbation by approximately 70%.
- Patients hospitalized for a severe exacerbation may face about a 20% risk of readmission within 30 days, Bhatt said.
- Within 90 days, approximately 35% to 40% of patients may be readmitted or experience another exacerbation, according to his comments.
- He said hospital readmission rates have remained around 18% to 20% for more than a decade.
Bhatt said the period immediately after an exacerbation is particularly vulnerable because patients are often discharged with a course of steroids and antibiotics but may not see a specialist for two to four weeks. Existing biologic trials in stable COPD have generally excluded patients who recently experienced an exacerbation, he noted.
Seabreeze Results and Treatment Failure
Bhatt said the phase 2 Seabreeze COPD study evaluated a single dose of rademikibart administered during an exacerbation or within 48 hours of symptom onset. He characterized the approach as novel because biologic therapy has not typically been initiated during an acute COPD event.
He cited an 81% reduction in treatment failure in the COPD study, with treatment failure defined as another exacerbation, an emergency department visit, hospitalization or death. Bhatt said the finding requires confirmation in a larger phase 3 trial but called the result “very impressive.”
While he said a 20% reduction in hospital readmissions is often viewed as clinically meaningful in trial design, he added that a 35% to 40% reduction in treatment failure for a biologic would be “quite remarkable.” Emergency department visits and hospitalizations are among the most clinically important components of treatment failure, he said, because they are more objective than outpatient treatment intensification and carry substantial patient and healthcare-system costs.
Bhatt noted that Seabreeze’s observed event rate appeared lower than he would have expected based on real-world data, where 30-day treatment failure rates have generally ranged from the mid-20% range to the low-30% range. He said seeing a marked treatment effect despite a lower event rate was encouraging, though he did not draw conclusions about future trial outcomes.
Lung Function Findings
Bhatt said the absence of a clear early separation in forced expiratory volume in one second, or FEV1, would not necessarily conflict with a reduction in treatment failure in acute COPD. Patients in both treatment arms received intensive background therapy, including corticosteroids and bronchodilators, which may limit the ability to detect an early incremental lung-function benefit, he said.
He added that COPD studies have often shown a disconnect between improvements in exacerbation frequency and changes in FEV1. In Seabreeze, he said both groups saw roughly 120 milliliters of FEV1 improvement, while the placebo-adjusted difference at about four weeks was approximately 70 milliliters. Bhatt said that result was directionally consistent with the roughly 80-milliliter improvement reported in stable-COPD dupilumab studies, while cautioning against direct comparisons across trials.
Potential Phase 3 Considerations
If designing a phase 3 study, Bhatt said he would favor treatment failure or an exacerbation-related endpoint as the primary measure, potentially within a hybrid design that starts therapy during an acute event and continues treatment for about 52 weeks. Such a study could assess both short-term treatment failure and longer-term prevention of exacerbations, he said.
He said FEV1 could serve as a key secondary endpoint rather than the primary endpoint. Bhatt suggested that measuring lung-function area under the curve could be preferable to relying on a single time point, given day-to-day variability in FEV1 and the recovery process following an acute exacerbation.
Bhatt also said a phase 3 trial should consider enrolling both emergency-department-treated and hospitalized patients, rather than only severe hospitalized cases. He said moderate exacerbations can also contribute to future disease progression and higher risk of subsequent events.
Rademikibart targets type 2 inflammation, according to Bhatt, and the potential acute COPD population would include patients with elevated eosinophils or other indicators of type 2 inflammation. He estimated that blood eosinophil measurements identify type 2 inflammation in roughly the mid-20% range of COPD patients, while more sensitive testing approaches could identify up to 40%.
Bhatt concluded that phase 3 confirmation remains the key unanswered question, but said the phase 2 findings support further study of rademikibart as an acute-treatment option for COPD exacerbations.
About Connect Biopharma (NASDAQ:CNTB)
Connect Biopharma Corp. is a clinical-stage biopharmaceutical company focused on developing therapies for chronic inflammatory diseases driven by T-cell activity. The company uses its drug-discovery platform to identify and advance small-molecule and antibody-based treatments intended to selectively regulate immune responses while limiting broader immunosuppression.
Its pipeline has included ropsacitinib, formerly known as CBP-307, an oral selective sphingosine-1-phosphate receptor 1 modulator investigated for inflammatory bowel diseases such as ulcerative colitis and Crohn’s disease.
