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according to a new study published in Gastroenterology.
Latiglutenase led to 95% gluten degradation in the stomach, as indicated by measurements of gluten-immunogenic peptides in urine, wrote Joseph A. Murray, MD, a gastroenterologist at the Mayo Clinic, Rochester, Minn., and Jack A. Syage, PhD, CEO and cofounder of ImmunogenX Inc., Newport Beach, Calif., and colleagues on behalf of the CeliacShield Study Group.
For patients with celiac disease, the only available treatment is a life-long gluten-free diet (GFD). Low levels of gluten exposure can lead to ongoing inflammation and the risk of complications, and about half of patients continue to experience moderate to severe symptoms.
“Although a GFD can reduce symptoms and intestinal damage, the diet is neither easy nor readily achievable by many patients and, furthermore, can be lacking in essential nutrients,” the authors wrote.
In a randomized, double-blind, placebo-controlled gluten challenge study, the research team assessed the efficacy and safety of a 1,200-mg dose of IMGX003, formerly known as ALV003. The dual-enzyme supplementation therapy was “designed to mitigate the impact of gluten exposure in patients who are attempting to adhere to a GFD.”
The phase 2 trial was conducted at the Mayo Clinic with adult patients (aged 18-80 years) who had physician-diagnosed and biopsy-confirmed celiac disease, followed a GFD for more than 1 year, and had histologically well-controlled disease. During the study, they were exposed to 2 g of gluten per day for 6 weeks.
The primary endpoint focused on the change in the ratio of villus height to crypt depth. The “secondary endpoints included density of intraepithelial lymphocytes and symptom severity. Additional endpoints included serology and gluten-immunogenic peptides in urine.”
Among the 50 patients randomized, 43 completed the study, with 21 assigned to the IMGX003 group. About 74% of the participants were women; the mean age of all participants was 43.8 years.
Overall, the mean change in the ratio of villus height to crypt depth was –0.04 for IMGX003, compared with –0.35 for placebo. In addition, the mean change in the density of intraepithelial lymphocytes for IMGX003 was 9.8, compared with 24.8 for placebo. Based on the ratio of the means for both groups, the researchers estimated an 88% reduction of change in villus height to crypt depth and a 60% reduction of change in intraepithelial lymphocytes.
The mean changes, or worsening from baseline, in symptom severity for IMGX003 vs. placebo were 0.22 vs. 1.63 for abdominal pain, 0.96 vs. 3.29 for bloating, 0.02 vs. 3.2 for tiredness, and 0.64 vs. 2.27 for nonstool composite. The calculated symptom reduction values were 93% for abdominal pain, 53% for bloating, 99% for tiredness, and 70% for nonstool composite.
The mean change from baseline for symptom severity was evaluated over three 2-week periods, and the percent changes showed consistent reduction of symptom worsening during that time. Based on the effect size and trend significance, the P values were .014 for abdominal pain, .030 for bloating, .002 for tiredness, and < . 001 for nonstool composite.
The mean change in gluten-immunogenic peptides in urine (GIP) relative to baseline was 0.59 for IMGX003, compared with 11.53 for placebo. The researchers estimated an efficacy of gluten degradation in vivo of 95%.
“Measurement of GIP in urine demonstrated the purported mechanism of action of IMGX003, namely, degradation of gluten in the stomach, thereby preventing the triggering of the immunogenic autoimmune response,” the authors wrote. “Targeting gluten by degrading the immunogenic peptides before absorption minimizes or abrogates the cascading innate and adaptive immune responses that characterize the inflammatory response to gluten in CeD [celiac disease].”
The study was sponsored by ImmunogenX Inc., and partially funded by a grant from the National Center for Complementary and Integrative Health. The project was further supported by grants from the National Center for Advancing Translational Sciences and the National Institute of Diabetes and Digestive and Kidney Diseases. Several authors reported receiving grants from numerous funders, including ImmunogenX, and some reported being a cofounder, stockholder, or board director of the company.
From the perspective of patients affected by other chronic GI diseases requiring constant treatment with drugs, the life of celiac patients must appear “a piece of cake” (pun intended). But this is not the case. In fact, the burden of following a gluten-free diet (GFD) can profoundly impact their quality of life. Furthermore, a substantial portion of patients trying their best on a GFD do not experience full clinical and histologic remission, mainly because of ongoing involuntary gluten ingestion. Therefore, it’s not surprising that several lines of research have been actively trying to address this unmet need.
In this phase 2 trial, the proprietary enzyme combination called IMGX003 (latiglutenase) was investigated for safety and efficacy. IMGX003 can digest gluten in the stomach, thus preventing its intact entry into the small intestine where it would trigger the immune reaction leading to the villi destruction. The study did indeed demonstrate that administering it to patients on GFD exposed to 2 grams of gluten daily (roughly the equivalent of half a slice of wheat bread) effectively reduced both the mucosal damage and symptom severity. Is this good news for patients with celiac? You bet it is! While not replacing the need for a GFD, having a safe drug that adds a substantial layer of protection to inadvertent gluten exposure or the so-called “cross-contamination” is surely to be welcome by them.
If and once approved for use, IMGX003 could be taken sporadically by patients on GFD: For instance, while eating out in “new” places, traveling, going to parties, or for younger patients, when having sleepovers, birthday celebrations, and so on. With the caveat, not to be forgotten, that this is not meant to be a wonder drug eliminating the need for vigilance; we still need to wait patiently for science to advance further for that.
Stefano Guandalini, MD, AGAF, is professor emeritus of pediatrics at the University of Chicago and director emeritus of the University of Chicago Celiac Disease Center. He declares no relevant conflicts of interest.
From the perspective of patients affected by other chronic GI diseases requiring constant treatment with drugs, the life of celiac patients must appear “a piece of cake” (pun intended). But this is not the case. In fact, the burden of following a gluten-free diet (GFD) can profoundly impact their quality of life. Furthermore, a substantial portion of patients trying their best on a GFD do not experience full clinical and histologic remission, mainly because of ongoing involuntary gluten ingestion. Therefore, it’s not surprising that several lines of research have been actively trying to address this unmet need.
In this phase 2 trial, the proprietary enzyme combination called IMGX003 (latiglutenase) was investigated for safety and efficacy. IMGX003 can digest gluten in the stomach, thus preventing its intact entry into the small intestine where it would trigger the immune reaction leading to the villi destruction. The study did indeed demonstrate that administering it to patients on GFD exposed to 2 grams of gluten daily (roughly the equivalent of half a slice of wheat bread) effectively reduced both the mucosal damage and symptom severity. Is this good news for patients with celiac? You bet it is! While not replacing the need for a GFD, having a safe drug that adds a substantial layer of protection to inadvertent gluten exposure or the so-called “cross-contamination” is surely to be welcome by them.
If and once approved for use, IMGX003 could be taken sporadically by patients on GFD: For instance, while eating out in “new” places, traveling, going to parties, or for younger patients, when having sleepovers, birthday celebrations, and so on. With the caveat, not to be forgotten, that this is not meant to be a wonder drug eliminating the need for vigilance; we still need to wait patiently for science to advance further for that.
Stefano Guandalini, MD, AGAF, is professor emeritus of pediatrics at the University of Chicago and director emeritus of the University of Chicago Celiac Disease Center. He declares no relevant conflicts of interest.
From the perspective of patients affected by other chronic GI diseases requiring constant treatment with drugs, the life of celiac patients must appear “a piece of cake” (pun intended). But this is not the case. In fact, the burden of following a gluten-free diet (GFD) can profoundly impact their quality of life. Furthermore, a substantial portion of patients trying their best on a GFD do not experience full clinical and histologic remission, mainly because of ongoing involuntary gluten ingestion. Therefore, it’s not surprising that several lines of research have been actively trying to address this unmet need.
In this phase 2 trial, the proprietary enzyme combination called IMGX003 (latiglutenase) was investigated for safety and efficacy. IMGX003 can digest gluten in the stomach, thus preventing its intact entry into the small intestine where it would trigger the immune reaction leading to the villi destruction. The study did indeed demonstrate that administering it to patients on GFD exposed to 2 grams of gluten daily (roughly the equivalent of half a slice of wheat bread) effectively reduced both the mucosal damage and symptom severity. Is this good news for patients with celiac? You bet it is! While not replacing the need for a GFD, having a safe drug that adds a substantial layer of protection to inadvertent gluten exposure or the so-called “cross-contamination” is surely to be welcome by them.
If and once approved for use, IMGX003 could be taken sporadically by patients on GFD: For instance, while eating out in “new” places, traveling, going to parties, or for younger patients, when having sleepovers, birthday celebrations, and so on. With the caveat, not to be forgotten, that this is not meant to be a wonder drug eliminating the need for vigilance; we still need to wait patiently for science to advance further for that.
Stefano Guandalini, MD, AGAF, is professor emeritus of pediatrics at the University of Chicago and director emeritus of the University of Chicago Celiac Disease Center. He declares no relevant conflicts of interest.
according to a new study published in Gastroenterology.
Latiglutenase led to 95% gluten degradation in the stomach, as indicated by measurements of gluten-immunogenic peptides in urine, wrote Joseph A. Murray, MD, a gastroenterologist at the Mayo Clinic, Rochester, Minn., and Jack A. Syage, PhD, CEO and cofounder of ImmunogenX Inc., Newport Beach, Calif., and colleagues on behalf of the CeliacShield Study Group.
For patients with celiac disease, the only available treatment is a life-long gluten-free diet (GFD). Low levels of gluten exposure can lead to ongoing inflammation and the risk of complications, and about half of patients continue to experience moderate to severe symptoms.
“Although a GFD can reduce symptoms and intestinal damage, the diet is neither easy nor readily achievable by many patients and, furthermore, can be lacking in essential nutrients,” the authors wrote.
In a randomized, double-blind, placebo-controlled gluten challenge study, the research team assessed the efficacy and safety of a 1,200-mg dose of IMGX003, formerly known as ALV003. The dual-enzyme supplementation therapy was “designed to mitigate the impact of gluten exposure in patients who are attempting to adhere to a GFD.”
The phase 2 trial was conducted at the Mayo Clinic with adult patients (aged 18-80 years) who had physician-diagnosed and biopsy-confirmed celiac disease, followed a GFD for more than 1 year, and had histologically well-controlled disease. During the study, they were exposed to 2 g of gluten per day for 6 weeks.
The primary endpoint focused on the change in the ratio of villus height to crypt depth. The “secondary endpoints included density of intraepithelial lymphocytes and symptom severity. Additional endpoints included serology and gluten-immunogenic peptides in urine.”
Among the 50 patients randomized, 43 completed the study, with 21 assigned to the IMGX003 group. About 74% of the participants were women; the mean age of all participants was 43.8 years.
Overall, the mean change in the ratio of villus height to crypt depth was –0.04 for IMGX003, compared with –0.35 for placebo. In addition, the mean change in the density of intraepithelial lymphocytes for IMGX003 was 9.8, compared with 24.8 for placebo. Based on the ratio of the means for both groups, the researchers estimated an 88% reduction of change in villus height to crypt depth and a 60% reduction of change in intraepithelial lymphocytes.
The mean changes, or worsening from baseline, in symptom severity for IMGX003 vs. placebo were 0.22 vs. 1.63 for abdominal pain, 0.96 vs. 3.29 for bloating, 0.02 vs. 3.2 for tiredness, and 0.64 vs. 2.27 for nonstool composite. The calculated symptom reduction values were 93% for abdominal pain, 53% for bloating, 99% for tiredness, and 70% for nonstool composite.
The mean change from baseline for symptom severity was evaluated over three 2-week periods, and the percent changes showed consistent reduction of symptom worsening during that time. Based on the effect size and trend significance, the P values were .014 for abdominal pain, .030 for bloating, .002 for tiredness, and < . 001 for nonstool composite.
The mean change in gluten-immunogenic peptides in urine (GIP) relative to baseline was 0.59 for IMGX003, compared with 11.53 for placebo. The researchers estimated an efficacy of gluten degradation in vivo of 95%.
“Measurement of GIP in urine demonstrated the purported mechanism of action of IMGX003, namely, degradation of gluten in the stomach, thereby preventing the triggering of the immunogenic autoimmune response,” the authors wrote. “Targeting gluten by degrading the immunogenic peptides before absorption minimizes or abrogates the cascading innate and adaptive immune responses that characterize the inflammatory response to gluten in CeD [celiac disease].”
The study was sponsored by ImmunogenX Inc., and partially funded by a grant from the National Center for Complementary and Integrative Health. The project was further supported by grants from the National Center for Advancing Translational Sciences and the National Institute of Diabetes and Digestive and Kidney Diseases. Several authors reported receiving grants from numerous funders, including ImmunogenX, and some reported being a cofounder, stockholder, or board director of the company.
according to a new study published in Gastroenterology.
Latiglutenase led to 95% gluten degradation in the stomach, as indicated by measurements of gluten-immunogenic peptides in urine, wrote Joseph A. Murray, MD, a gastroenterologist at the Mayo Clinic, Rochester, Minn., and Jack A. Syage, PhD, CEO and cofounder of ImmunogenX Inc., Newport Beach, Calif., and colleagues on behalf of the CeliacShield Study Group.
For patients with celiac disease, the only available treatment is a life-long gluten-free diet (GFD). Low levels of gluten exposure can lead to ongoing inflammation and the risk of complications, and about half of patients continue to experience moderate to severe symptoms.
“Although a GFD can reduce symptoms and intestinal damage, the diet is neither easy nor readily achievable by many patients and, furthermore, can be lacking in essential nutrients,” the authors wrote.
In a randomized, double-blind, placebo-controlled gluten challenge study, the research team assessed the efficacy and safety of a 1,200-mg dose of IMGX003, formerly known as ALV003. The dual-enzyme supplementation therapy was “designed to mitigate the impact of gluten exposure in patients who are attempting to adhere to a GFD.”
The phase 2 trial was conducted at the Mayo Clinic with adult patients (aged 18-80 years) who had physician-diagnosed and biopsy-confirmed celiac disease, followed a GFD for more than 1 year, and had histologically well-controlled disease. During the study, they were exposed to 2 g of gluten per day for 6 weeks.
The primary endpoint focused on the change in the ratio of villus height to crypt depth. The “secondary endpoints included density of intraepithelial lymphocytes and symptom severity. Additional endpoints included serology and gluten-immunogenic peptides in urine.”
Among the 50 patients randomized, 43 completed the study, with 21 assigned to the IMGX003 group. About 74% of the participants were women; the mean age of all participants was 43.8 years.
Overall, the mean change in the ratio of villus height to crypt depth was –0.04 for IMGX003, compared with –0.35 for placebo. In addition, the mean change in the density of intraepithelial lymphocytes for IMGX003 was 9.8, compared with 24.8 for placebo. Based on the ratio of the means for both groups, the researchers estimated an 88% reduction of change in villus height to crypt depth and a 60% reduction of change in intraepithelial lymphocytes.
The mean changes, or worsening from baseline, in symptom severity for IMGX003 vs. placebo were 0.22 vs. 1.63 for abdominal pain, 0.96 vs. 3.29 for bloating, 0.02 vs. 3.2 for tiredness, and 0.64 vs. 2.27 for nonstool composite. The calculated symptom reduction values were 93% for abdominal pain, 53% for bloating, 99% for tiredness, and 70% for nonstool composite.
The mean change from baseline for symptom severity was evaluated over three 2-week periods, and the percent changes showed consistent reduction of symptom worsening during that time. Based on the effect size and trend significance, the P values were .014 for abdominal pain, .030 for bloating, .002 for tiredness, and < . 001 for nonstool composite.
The mean change in gluten-immunogenic peptides in urine (GIP) relative to baseline was 0.59 for IMGX003, compared with 11.53 for placebo. The researchers estimated an efficacy of gluten degradation in vivo of 95%.
“Measurement of GIP in urine demonstrated the purported mechanism of action of IMGX003, namely, degradation of gluten in the stomach, thereby preventing the triggering of the immunogenic autoimmune response,” the authors wrote. “Targeting gluten by degrading the immunogenic peptides before absorption minimizes or abrogates the cascading innate and adaptive immune responses that characterize the inflammatory response to gluten in CeD [celiac disease].”
The study was sponsored by ImmunogenX Inc., and partially funded by a grant from the National Center for Complementary and Integrative Health. The project was further supported by grants from the National Center for Advancing Translational Sciences and the National Institute of Diabetes and Digestive and Kidney Diseases. Several authors reported receiving grants from numerous funders, including ImmunogenX, and some reported being a cofounder, stockholder, or board director of the company.
FROM GASTROENTEROLOGY