RARE Daily

Eloxx, After Remission of an Alport Syndrome Patient, Plans to Advance Lead Therapy to Phase 3

May 25, 2023

Rare Daily Staff

Eloxx Pharmaceuticals said it will advance its experimental therapy ELX-02 to a pivotal trial for the treatment of Alport syndrome with nonsense mutations.

The decision follows a phase 2 study in which an Alport syndrome patient achieved remission. The patient demonstrated a significant reduction in urine protein creatinine ratio (UPCR) from baseline. Consistent with prior clinical studies, ELX-02 was well tolerated in this trial.

The decision comes after ELX-02 in combination with ivacaftor failed to demonstrate statistical significance for efficacy endpoints in mid-stage study in cystic fibrosis last year.

“The achievement of a remission in one of the first two patients with Alport syndrome with nonsense mutations in this trial of ELX-02 is a very encouraging result, as patients with this rare disease rarely demonstrate a reduction in proteinuria,” said Detlef Bockenhauer, professor of Pediatric Nephrology at University College London. “Based on the efficacy and tolerability to date, additional clinical testing is warranted in this patient population in need of disease-modifying treatments.”

Alport syndrome is a genetic disorder characterized by kidney disease with high levels of proteinuria, hearing loss and eye abnormalities caused by mutations in the genes COL4A3, COL4A4, and COL4A5 needed for production of type 4 collagen. About 6 percent to 7 percent of Alport syndrome patients, or approximately 9,400 to 12,750 individuals, are estimated to have nonsense mutations. These patients have significantly worse clinical outcomes than other Alport patients and have no disease modifying treatment options.

Nonsense mutations cause a premature stop codon in the mRNA resulting in less than full length or loss of function proteins. An estimated 10 to 12 percent of patients across more than 8,000 inherited genetic rare diseases harbor nonsense mutations in one or both alleles harboring nonsense mutations.

Eloxx’s lead investigational product candidate, ELX-02, is a small molecule drug candidate designed to restore production of full-length functional proteins.

Eloxx has dosed three patients with ELX-02 in the ongoing proof-of-concept phase 2 open-label clinical trial. Two patients have now completed dosing and the third patient is still receiving ELX-02.

One patient that has completed dosing achieved a remission, defined as a UPCR decline greater than or equal to 50 percent. For this patient, five out of eight UPCR readings produced an average of 53 percent below baseline. Spontaneous reductions in proteinuria are not expected in this population, providing added weight to this result.

The patient achieving remission also demonstrated a significant reduction (-49 percent) in UPCR from baseline versus values collected over the treatment period.

Consistent with previous clinical studies, ELX-02 has been generally well tolerated with no discontinuations to date.

Sumit Aggarwal, president and CEO of Eloxx, said Alport syndrome patients with nonsense mutations  have significant unmet medical needs, with no disease modifying treatments currently available.

“Following completion of the third patient in the trial,” he said, “we plan to discuss the findings with the FDA with the goal of advancing the program into a pivotal trial, pending obtaining the necessary capital.”

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