JERUSALEM—Dedicated to developing effective treatments for significant unmet medical needs, biopharmaceutical company BioLineRx Ltd. has declared the successful final results from its Phase 1/2 study of BL-7010, a new co-polymer created to treat celiac disease, a digestive malady with no “cure,” but which requires strict adherence to a gluten-free diet. If BL-7010 meets its expectations, people suffering from celiac disease soon won’t have to worry about random gluten creeping into their digestive systems and wreaking havoc.
BL-7010 was invented by Prof. Jean-Christophe Leroux from the Department of Chemistry and Applied Biosciences at the Institute of Pharmaceutical Sciences in Zurich, Switzerland, and is being developed by BioLineRx under a worldwide exclusive license agreement with Montreal-based Univalor.
Over the next few months, BioLineRx will conduct additional nonclinical studies and formulation development for BL-7010 to prepare for an upcoming randomized, placebo-controlled efficacy study, slated for the second half of 2015.
“BL-7010 for the treatment of celiac disease is one of our lead clinical programs, and we are very pleased with the positive final results of this Phase 1/2 safety study and the determination of the optimal safe dose for continued development,” BioLineRx CEO Dr. Kinneret Savitsky stated in a news release.
Celiac disease is highly prevalent throughout the world, with more than 1 percent of the global population suffering from it (including 2.5 million Americans), according to the Celiac Disease Foundation.
Celiac disease is a chronic, autoimmune, inflammatory disease of the small intestine characterized by damage to the lining of the small intestine, and it typically leads to dyspepsia, malabsorption and a variety of other symptoms. It occurs in genetically predisposed individuals and is caused by an immunological reaction to gluten, found in wheat, barley and rye.
The celiac market is projected to reach $8 billion by 2019, BioLineRx reports. There are currently no treatments approved for celiac disease, and the only option is a lifelong, strict, gluten-free diet, which is costly and difficult to maintain due to food contamination with gluten and eating habits in social settings.
“BL-7010 will protect celiac patients that are maintaining a gluten-free diet from accidental exposure to gluten during their daily life and will not replace the gluten-free diet,” Savitsky tells DDNews. “This accidental exposure results in gastrointestinal symptoms in a large percentage of the patients and has long-lasting negative effects.”
“Despite the significant need for new treatments, there are only a handful of clinical-stage projects under development worldwide for this disease, which we view as a significant opportunity for our product,” she noted in the news release.
BL-7010 will be taken orally as a tablet (other oral forms are also possible for specific populations, such as children), she said. BL-7010 is intended to be taken together with each main meal every day in order to avoid residual exposure to gluten in the meal.
BioLineRx chose celiac disease to study over other diseases “because of its significant medical need for celiac patients,” Savitsky says. “Bioline has an in-licensing forum in which we review many projects per year. As part of the due diligence process, we also try to have a clear understanding of the medical need. In the case of BL-7010, it was clear that there is a significant medical need for celiac patients.”
Moreover, about 20 to 30 percent of the celiac population, though on gluten-free diets, are still symptomatic due to accidental exposure to gluten during daily living, she notes.
In the successful study, BL-7010 was tested in celiac patients that are stable (i.e. nonsymptomatic) while following a strict, gluten-free diet, Savitsky says. This initial safety study included several escalating single doses followed by repeated administration of the product three times daily for 14 days.
Based on its strong safety and tolerability profile, BioLine has selected the one-gram, three-times-per-day regimen of BL-7010 as the optimal repeated dose for the upcoming efficacy study. Decreasing the dose to these levels substantially reduced the gastrointestinal-related adverse events (primarily diarrhea) observed previously at higher doses, while remaining within the anticipated therapeutic window for BL-7010 based on nonclinical studies.
“This next planned study will be a gluten challenge study in which celiac patients that are stable while following a strict, gluten-free diet will be exposed to a controlled amount of gluten and in a randomized, double-blind fashion will be treated with BL-7010 or placebo,” Savitsky explains. “The aim of this study will be to show that treatment with BL-7010 with each meal can protect against the development of damage to the gastrointestinal tract.”
The nonpharmacological mode of action of BL-7010, together with the lack of BL-7010 systemic exposure demonstrated in animals and humans, will likely support medical-device classification in the European Union, she said. This classification will significantly accelerate the development in Europe.
“That is the reason we are targeting the European Union as the first territory for registration,” Savitsky says. “Obviously, BioLine is also interested in the registration of BL-7010 in the U.S., and we expect that BL-7010 will be classified in the U.S. as a drug, and the development plan will include Phase 2 and Phase 3 studies. We plan to approach the FDA and discuss the development plan in the U.S. in a pre-IND meeting.”
The Phase 1/2 study was a two-part (single and repeated administration), double-blind, placebo-controlled, dose-ranging study of BL-7010 in well-controlled celiac patients. The primary objective of the study was to assess the safety of single and repeated ascending doses of BL-7010. Secondary objectives include an assessment of the compound’s systemic exposure, if any. During the single-administration part of the study, several dose levels of BL-7010 were evaluated compared to placebo in a 6+2 standard design, with six patients receiving BL-7010 and two patients receiving placebo at each dose level. During the repeated-administration part of the study, several doses of either BL-7010 or placebo were tested for 14 days (three times per day) in the same 6+2 standard design. A total of 32 patients participated in the study, most of whom received more than one dose level of BL-7010 or placebo.
BL-7010 is a novel, non-absorbable, orally available co-polymer intended for the treatment of celiac disease. It has a high affinity for gliadins, the immunogenic proteins present in gluten that cause celiac disease. By sequestering gliadins, BL-7010 effectively masks them from enzymatic degradation and prevents the formation of immunogenic peptides that trigger the immune system. This significantly reduces the immune response triggered by gluten. BL-7010 is excreted with gliadin from the digestive tract and is not absorbed into the blood. The safety and efficacy of BL-7010 have been demonstrated in preclinical and clinical studies.