ELX-02 monotherapy dosed at 1.5mg/kg/day demonstrated a statistically significant 5.4mmol/L mean sweat chloride reduction, an established surrogate for restoration of CFTR biological activity
ELX-02 monotherapy results support advancement of ELX-02 into Phase 3 clinical development
First patient dosed in Phase 2 ELX-02 expansion treatment arms evaluating combination with ivacaftor; topline data expected by the end of the first half of 2022
Company to host conference call and webcast
The intra-patient dose escalation stage of the trial has successfully identified 1.5 mg/kg/day as the dose for further development. Based on the statistically significant monotherapy results observed at the 1.5mg/kg/day dose, planning for the advancement of ELX-02 into Phase 3 clinical development has started. The
“We are highly encouraged with the topline results from the monotherapy arms of our Phase 2 trial, and believe that ELX-02, if approved, has potential to transform the lives of Class 1 CF patients with nonsense mutations, who do not have any available therapies,” said
Topline Results of ELX-02 Phase 2 Monotherapy Trial in Class 1 Nonsense CF Patients
The Phase 2 clinical trial of ELX-02 was designed to evaluate safety and assess biological activity in G542X nonsense mutation Class 1 CF patients as monotherapy and in combination with ivacaftor. Topline results for the intra-patient dose escalation monotherapy arms are summarized below:
- ELX-02 was generally well tolerated in the trial, with no treatment-related serious adverse events noted.
- The study met a key secondary endpoint by showing a statistically significant reduction in mean sweat chloride of 5.4 mmol/L (p value=0.0218, n=12 patients) after one week of therapy for ELX-02 dosed at 1.5mg/kg/day.
- Short term reductions in sweat chloride have been shown to correlate with biologic activity of the CFTR protein and translate to lung function improvement over the long term.
- A potential dose response trend was also seen in mean sweat chloride reduction, with a stronger dose response trend in the subset of patients (post-hoc) that completed the 1.5mg/kg/day dosing.
- The reduction in mean sweat chloride in Class 1 CF patients with nonsense mutations who received 1.5mg/kg/day in the trial is similar to the activity in Class 1 CF patient organoids treated with ELX-02 in preclinical experiments.
- As expected, no change was observed in forced expiratory volume (FEV1) due to short treatment duration.
- While the trial was not designed as a longer-term efficacy study and did not compare ELX-02 to any other agent, results from prior Phase 2 trials with FDA-approved agents for CF can serve as a contextual reference for the level of sweat chloride reduction observed and its potential clinical relevance.
- Results of a Phase 2 study with lumacaftor and lumacaftor/ivacaftor combination (Orkambi), an FDA-approved combination CF agent, demonstrated 4.1mmol/L to 5.1 mmol/L reductions in sweat chloride over two- and three-week study durations in Class 2 CF patients with HomF50del mutations.
- Results of a phase 2 study with tezacoftor/ivacaftor combination (Symdeko), an FDA-approved combination CF agent, demonstrated a 1.8mmol/L to 5.2 mmol/L reduction in sweat chloride over 28 days in Class 2 CF patients with HomF50del mutations.
- Treatment with both these agents resulted in improved lung function as measured by forced expiratory volume FEV1 with longer treatment duration in subsequent Phase 3 trials with Orkambi and Symdeko.
“These significant results for sweat chloride, a surrogate for CFTR protein function in patients, are very exciting. I look forward to working with Eloxx on future development of ELX-02,” said Prof.
Planned Next Steps for ELX-02 CF Program
ELX-02 in combination with other CF therapies.
First patient dosing has occurred in the expansion arm of the Phase 2 trial, which includes a combination of ELX-02 and Kalydeco (ivacaftor), a CFTR protein potentiator. In preclinical studies, Class 1 CF patient organoids had a 2- to 3-fold higher swelling response with a combination of ELX-02 and Kalydeco than with ELX-02 as a monotherapy. Topline results are expected by the end of the first half of 2022.
“With dosing of the first patient, we have now advanced ELX-02 into the Phase 2 combination study and have begun preparations for Phase 3 clinical development,” said
Inhaled delivery of ELX-02
Eloxx has also begun evaluation of inhaled (nebulizer-based) delivery of the current subcutaneous formulation of ELX-02. Eloxx believes that inhaled delivery has the potential to further improve the activity of ELX-02 as a single agent and in combination with other drugs given potential for increased drug exposure in the lung versus plasma. Prior animal studies have shown a 19-fold increase in ELX-02 exposure at a similar dose when administered as an inhalation agent versus subcutaneously. We expect to submit an Investigational New Drug application the second half of 2022.
About Class 1 CF
CF patients with a Class 1 nonsense mutation remain highly underserved with no approved disease modifying therapies. An estimated 10-12% of CF patients are Class 1 patients with one or both alleles harboring nonsense mutations, leading to less than full length CFTR proteins on the cell membrane in these patients.
Conference Call and Webcast
Eloxx’s management will host a conference call and webcast today at
For more information, please visit www.eloxxpharma.com.
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements other than statements of present and historical facts contained in this press release, including without limitation, statements regarding our expected cash burn and future financial results, the expected timing of trials and results from clinical studies of our product candidates and the potential of our product candidate to treat nonsense mutations are forward-looking statements. Forward-looking statements can be identified by the words “aim,” “may,” “will,” “would,” “should,” “expect,” “explore,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “potential,” “seeks,” or “continue” or the negative of these terms similar expressions, although not all forward-looking statements contain these words.
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Source: Eloxx Pharmaceuticals