Patients with celiac disease who were seropositive despite adhering to a gluten-free diet experienced significant improvement in symptoms when taking latiglutenase with meals, according to a post hoc analysis of the CeliAction study.
Latiglutenase (ImmunogenX; formerly ALV003, Alvine) is an enzyme supplementation therapy containing two recombinant proteins designed to degrade gluten into non-immunotoxic fragments when taken with meals, thereby preventing exposure in patients with celiac disease.
“Though the ALV003-1221 trial was inconclusive regarding histologic improvement from latiglutenase, the evidence for symptom benefit, which is more quickly achieved, is quite convincing and clinically relevant,” Joseph Murray, MD, of the Mayo Clinic in Rochester, Minn., said in a press release. “This subanalysis demonstrates that a therapy to help patients struggling with symptoms due to celiac disease is now within reach.”
The phase 2 trial involved 494 celiac patients with moderate-to-severe symptoms in North America and Europe who adhered to a gluten-free diet for at least 1 year prior and throughout the trial. Murray and colleagues randomly assigned them to receive placebo or one of five doses of latiglutenase daily for 12 weeks. Histological improvement served as the primary endpoint, which the study failed to meet, possibly “due to a strong trial effect,” according to investigators.
In this post hoc analysis, Murray and colleagues re-evaluated symptomatic endpoints in the 298 patients who completed the trial, 43% of whom were seropositive at baseline.
They found a statistically significant, dose-dependent reduction in the severity and frequency of symptoms (abdominal pain, bloating, tiredness and constipation) in these patients who were seropositive at trial entry despite being on a gluten-free diet, but not in seronegative patients.
Abdominal pain severity dropped by 58% and bloating severity dropped by 44% in patients who received the highest dose (900 mg) compared with placebo.
The investigators also noted that symptom improvement increased between weeks 6 and 12, and patients with greater symptom severity at baseline tended to have better symptom improvement.
The “significant differentiation in symptom improvement, but not histologic improvement, for high dose versus placebo arms may be attributable to the different time scales required for histologic improvement, compared to symptom improvement, as well as the poor correlation between symptoms severity and same degree of villous atrophy and gluten ingestion,” Murray and colleagues wrote.
“The CeliAction trial is the largest therapeutic trial conducted for celiac disease to date and showed that latiglutenase can attenuate symptoms of celiac disease in patients who remain seropositive,” Jennifer Sealey-Voyksner, PhD, CSO of ImmunogenX, said in the press release. “This subclass of patients represents the 10-20% of patients who are most burdened by the disease. As a diagnosed celiac patient myself, it is very gratifying to be able to offer a new therapeutic option pending successful completion of the clinical development program and FDA approval.” – by Adam Leitenberger
Disclosures: Murray reports he has received grant support from the NIH, Alvine Pharmaceuticals and Alba Therapeutics, and receives ongoing support from Oberkotter Foundation and Broad Medical Research Program at CCFA. He also serves on the advisory board of Celimmune and ImmunoGenx, was a consultant to BioLineRx, GlaxoSmithKline, Genentech and Glenmark Pharmaceuticals, and currently serves as a consultant to ImmunosanT, Institute for Protein Design (PvP Biologics), Takeda Pharmaceuticals, Innovate Biopharmaceuticals and Intrexon. Please see the full study for a list of all other researcher’s relevant financial disclosures. Sealey-Voyksner is employed by ImmunogenX.