The trial will be led in the U.S. by Ahmet Uluer, DO, director of the Adult Cystic Fibrosis Program at the Boston Children’s Hospital/Brigham and Women’s Hospital CF Center. Kerem Eitan, MD, head of the division of pediatrics at the Children’s Hospital of Hadassah Medical Center, in Israel, will serve as the global lead investigator.
The company also announced that the trial’s protocol was approved by the Cystic Fibrosis Foundation (CFF).
“We are very pleased that our IND is open in the U.S., and the protocol for our Phase 2 clinical trial in cystic fibrosis has been endorsed by the Cystic Fibrosis Foundation (CFF),” Robert E. Ward, chairman and CEO of Eloxx Pharmaceuticals, said in a press release.
“We believe that the positive data we have generated for ELX-02 in cystic fibrosis patient-derived organoids substantially de-risk our Phase 2 program,” Ward added.
ELX-02 is a small molecule that was designed to target nonsense genetic mutations. It restores the activity of previously nonfunctional, or nonworking proteins that cause CF and cystinosis. This investigational compound has received orphan medicine status by the European Medicines Agency (EMA) for the treatment of CF and mucopolysaccharidosis type I (MPS I). It also ha been granted orphan drug designation by the FDA for cystinosis, MPS I, and Rett Syndrome.
Preclinical studies using patient-derived organoids — a type of “mini-organs” that are grown in the lab from patient cells, and that mimic disease-related mechanism — showed that treatment with ELX-02 could effectively increase the levels of functional CFTR protein, which is faulty in CF patients.
The treatment also could correct CFTR protein placement at the cell’s surface in organoids that are derived from cells with the most common CF-causing nonsense mutations, G542X and W1282X.
“ELX-02 is the only therapy to have demonstrated positive results in organoids derived from cystic fibrosis patients across the majority of nonsense mutations and studies have shown the organoid model to be highly predictive of clinical benefit,” Uluer said.
The safety and potential of ELX-02 was explored in a Phase 1 trial in healthy volunteers (NCT03309605). The data showed that different doses of ELX-02 were in general well-tolerated, and that the treatment could be safely administrated with no serious signs of toxicity.
“While important progress has been made in the development of disease modifying treatments for patients with cystic fibrosis, patients with nonsense mutations represent the most severe phenotypes and often do not respond to currently available therapies,” Eitan said. “I am excited to lead this clinical trial of ELX-02 which may provide a new therapeutic approach for these patients.”
Eloxx Pharmaceuticals expects to announce top line data on this new Phase 2 trial later in 2019. The company also is on track to report top line data from a Phase 2 clinical trial in Canada testing ELX-02 as a treatment for people with cystinosis, a condition characterized by the accumulation of the amino acid cystine, a building block of proteins, within cells. Excess cystine damages cells and often forms crystals that can build up and cause problems in many organs and tissues, particularly the kidneys and eyes.
A Phase 2 trial designed to assess the safety and tolerability of ELX-02 in people with cystinosis has just been initiated in Canada, the company announced in a press release.