XOMA Initiates Proof-of-Concept Study for XOMA 358 in Patients with Congenital Hyperinsulinism
BERKELEY, Calif., Oct. 26, 2015 (GLOBE NEWSWIRE) -- XOMA Corporation (Nasdaq:XOMA), a leader in the discovery and development of therapeutic antibodies, announced today it has initiated a Phase 2 proof-of-concept study to evaluate the safety and ability to prevent hypoglycemia (dangerously low blood sugar) of a single dose of XOMA 358 in patients with congenital hyperinsulinism (HI). XOMA 358 is a fully human allosteric monoclonal antibody that reduces insulin receptor activity.
HI is a genetic disorder in which the beta cells of the pancreas secrete excessive insulin that causes hypoglycemia, which can lead to brain damage or, in rare cases, death. HI is a rare disease, affecting approximately 1 in 50,000 newborns. The U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation to XOMA 358 for the treatment of HI.
"New treatments that safely and effectively attenuate insulin-induced hypoglycemia are needed for patients with congenital hyperinsulinism, as well as other diseases that cause hypoglycemia due to high insulin levels. There are no approved medications, and those currently used have inconsistent efficacy and issues with tolerability. Current disease management options are limited to continuous ingestion or infusion of glucose or surgical removal of part or all of the pancreas," said Paul Rubin, M.D., Senior Vice President, Research and Development, and Chief Medical Officer at XOMA. "We are developing XOMA 358 as a first-in-class therapeutic for patients with this potentially fatal disease, and we are pleased to be conducting this study at a world-class medical center recognized for its leadership in treating HI patients."
Proof-of-Concept Study Design
The open-label, single-administration study will evaluate XOMA 358 in congenital hyperinsulinism patients with documented hypoglycemia after a prolonged fast. Two cohorts of patients are planned, with the first cohort receiving a dose of XOMA 358 chosen based on the results from XOMA's Phase 1 study in healthy subjects. The second cohort of patients may receive a higher or lower dose dependent on the results seen in cohort 1. Patients will serve as their own control. The study will attempt to provoke and document hypoglycemic events due to fasting challenges prior to treatment with XOMA 358. Patients who experience hypoglycemia will be treated with XOMA 358 and then rechallenged by fasting at predetermined points in time to measure the potential impact and durability of XOMA 358 on hypoglycemia.
The study is open for patient enrollment at the Children's Hospital of Philadelphia (CHOP) and an additional international site is expected to open in the near-term. Safety will be monitored throughout the study. In addition, serial blood samples will be collected for pharmacokinetic and pharmacodynamic assessments. Various markers of drug activity will be assessed, including changes in glucose, ketones, insulin, C-peptide and free fatty acid levels. Controlled tests include monitored fasts, protein challenges, and oral glucose tolerance.
About XOMA 358
Insulin is the major physiologic hormone for controlling blood glucose levels. Abnormal increases in insulin secretion can lead to profound hypoglycemia (low blood sugar), a state that can result in significant morbidities, including brain damage, seizures and epilepsy. XOMA, leveraging its scientific expertise in allosteric monoclonal antibodies, developed the XMet platform, consisting of separate classes of selective insulin receptor modulators (SIRMs) that could have a major effect on treating patients with abnormal metabolic states. XOMA 358 binds selectively to insulin receptors and attenuates insulin action.
XOMA presented positive Phase 1 data on XOMA 358 at ENDO 2015, the Endocrine Society's annual meeting, in March 2015. Results of the study, in which 14 healthy volunteers received XOMA 358 and 5 received placebo, showed XOMA 358 reduced insulin sensitivity and decreased glucose lowering after exogenous insulin injection. In the study, XOMA 358 appeared to be well tolerated, with no serious adverse events observed.
XOMA 358 is being investigated as a novel treatment for non-drug-induced, endogenous hyperinsulinemic hypoglycemia, as well as hypoglycemia after post-bariatric surgery and other related disorders. A therapy that safely and effectively mitigates insulin-induced hypoglycemia has the potential to address a significant unmet therapeutic need for certain rare medical conditions associated with hyperinsulinism. More information on the XOMA 358 clinical trial may be found at www.clinicaltrials.gov.
About Congenital Hyperinsulinismi, ii, iii, iv
Congenital Hyperinsulinism (HI) is a genetic disorder in which the insulin cells of the pancreas (beta cells) secrete inappropriate and excessive insulin. Ordinarily, beta cells secrete just enough insulin to keep blood sugar in the normal range. In people with HI, the secretion of insulin is not properly regulated, causing excess insulin secretion and frequent episodes of low blood sugar (hypoglycemia). In infants and young children, these episodes are characterized by a lack of energy (lethargy), irritability or difficulty feeding. Repeated episodes of low blood sugar increase the risk for serious complications, such as breathing difficulties, seizures, intellectual disability, vision loss, brain damage, coma, and possibly death. About 60 percent of infants with HI experience a hypoglycemic episode within the first month of life. Other affected children develop hypoglycemia by early childhood. Current treatments for HI are limited to medical therapy and surgical removal of part or all of the pancreas (pancreatectomy).
About XOMA Corporation
XOMA Corporation is a leader in the discovery and development of therapeutic antibodies. The Company's innovative product candidates result from the Company's expertise in developing ground-breaking monoclonal antibodies, including allosteric antibodies, which have created new opportunities to potentially treat a wide range of human diseases. XOMA's scientific research has produced a portfolio of 6 endocrine assets, each of which have the opportunity to address multiple indications. The Company's lead product candidate, XOMA 358, is an allosteric monoclonal antibody that reduces insulin receptor activity, which could have a major effect on the treatment of hyperinsulinism. The Company recently initiated Phase 2 development activities for XOMA 358. Additionally, XOMA is developing gevokizumab (IL-1 beta modulating antibody) in an ongoing Phase 3 program enrolling patients with pyoderma gangrenosum, a rare ulcerative skin condition. For more information, visit www.xoma.com.
Certain statements contained in this press release including, but not limited to, statements related to anticipated timing of clinical trials, anticipated timing of the release of clinical data, regulatory approval of unapproved product candidates, the anticipated process of clinical data analysis, the anticipated success of any clinical trial, or statements that otherwise relate to future periods are forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. These statements are based on assumptions that may not prove accurate, and actual results could differ materially from those anticipated due to certain risks inherent in the biotechnology industry and for companies engaged in the development of new products in a regulated market. Potential risks to XOMA meeting these expectations are described in more detail in XOMA's most recent filing on Form 10-K and in other SEC filings. Consider such risks carefully when considering XOMA's prospects. Any forward-looking statement in this press release represents XOMA's views only as of the date of this press release and should not be relied upon as representing its views as of any subsequent date. XOMA disclaims any obligation to update any forward-looking statement, except as required by applicable law.
i ghr.nlm.nih.gov/condition/congenital-hyperinsulinism. Accessed June 11, 2015.
ii www.chop.edu/conditions-diseases/congenital-hyperinsulinism/about#.VXncFU3bKHt. Accessed June 11, 2015.
iii www.chop.edu/conditions-diseases/congenital-hyperinsulinism/about#.VXneYE3bKHu. Accessed June 11, 2015.
iv www.ojrd.com/content/pdf/1750-1172-6-63.pdf. Accessed June 11, 2015.
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Released October 26, 2015