Eloxx Adds Kalydeco to Ongoing Phase 2 Program Testing ELX-02

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by Steve Bryson PhD |

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Eloxx Pharmaceuticals has announced that it’s now added the approved cystic fibrosis (CF) therapy Kalydeco (ivacaftor) to its global Phase 2 clinical program for ELX-02.

Ongoing ELX-02 Phase 2 clinical trials, launched in 2019 with four treatment arms, are evaluating the safety and possible dosing of the investigational therapy for CF.

Now, a fifth treatment arm has been added to evaluate the safety of Kalydeco in combination with ELX-02 in CF patients with at least one G542X gene mutation.  

In both cell-based and animal models, ELX-02 combined with Kalydeco was found to further enhance the activity of the CFTR protein, which is defective in people with CF.

“We are extremely pleased to include this additional treatment arm in the ongoing Phase 2 clinical trial to further explore the potential of ELX-02 to treat cystic fibrosis,” Sumit Aggarwal, president and CEO of Eloxx, said in a press release.

ELX-02 is designed to target so-called nonsense mutations in the CFTR gene, the gene that is mutated in CF. This type of alteration in CFTR occurs in about 10% of patients worldwide. More than 70,000 people globally have CF.

G542X is the most common nonsense mutation in CF, and results in an imbalance that causes thick mucus to build up in the lungs, pancreas, liver, and intestines.  

The potential therapy works by helping cells’ protein-production machinery — called the ribosome — to generate a full-length, functional CFTR protein. That provides a way to improve the transport of water and chloride ions in and out of cells.

In previous preclinical studies with CF-causing nonsense mutations, ELX-02 effectively restored CFTR activity. 

Vertex Pharmaceuticals’ Kalydeco, known as a CFTR potentiator, is an approved therapy to treat CF patients with responsive mutations, working to help the ion channel (gate) stay open longer.

“Given ELX-02’s potential to treat CFTR nonsense mutations and the synergistic effects of ELX-02 and ivacaftor [Kalydeco] seen to date in pre-clinical models, we believe that combination treatment with a CFTR potentiator, such as ivacaftor, provides the opportunity to improve clinical efficacy in the treatment of CF,” Aggarwal said. 

ELX-02 is currently being evaluated in two open-label (no placebo) Phase 2 clinical trials, EL-004 (NCT04126473) and EL-012 (NCT04135495). In open-label trials, both participants and researchers know what medications are being given to the patients.

The two trials — currently running at sites in the U.S., Canada, Europe, Israel, and Australia — are assessing the therapy’s safety and pharmacological properties, at four increasing doses, in CF patients with at least one G542X mutation. Both studies are recruiting. More information is available here for the U.S. contacts and locations and here for the other study sites.

Following several planned Safety Review Committee meetings, dose escalation has been allowed up to the top dose level, with multiple patients progressing through the four-dose treatment phase. To date, no treatment-related serious adverse events have been reported, according to Eloxx.

Secondary outcomes measures in both trials include changes in the chloride concentration in sweat — participants are given a sweat test — as well as lung function tests. 

“We remain on track to present data from the first four treatment arms [groups] of the study in the second half of this year,” Aggarwal said. 

The Phase 2 clinical program is partially funded by the Cystic Fibrosis Foundation.

The U.S. Food and Drug Administration has granted ELX-02 orphan drug designation for the treatment of CF. That designation supports the development of treatments for people with rare diseases through financial incentives and seven years of marketing exclusivity, if the therapy is approved.


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