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Celtic Pharma Announces Results of a Phase III Program Evaluating XERECEPT® in Brain Tumors
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Celtic Pharmaceutical Holdings L.P. has reported at the American Society of Clinical Oncology meeting in Orlando the results of two randomized double-blind, placebo-controlled Phase III studies of XERECEPT® (corticorelin acetate), compared to dexamethasone, the current standard of care in the treatment of cerebral edema associated with brain tumors, and an open-label rollover Phase III study of XERECEPT’s long-term safety and effectiveness in these patients.
Celtic Pharma believes these studies demonstrate that XERECEPT® was well tolerated and enabled clinically significant reductions in corticosteroid use in patients with cerebral edema associated with both primary and metastatic brain tumors. The Company also announced the results of several preclinical studies demonstrating potential anti-tumor and angiogenesis inhibition effects of XERECEPT®.
"The ability to reduce the use of steroids and concomitant reduction in adverse side effects in the treatment of patients with brain tumors is an important goal,” said Lawrence Recht, MD, Professor of Neurology and Neurological Sciences, Stanford University Medical Center.
“The results of these late-stage studies are encouraging, both in terms of lowering dexamethasone use over the longer-term and the impact seen in metastatic patients, a large group with limited treatment options. The preclinical tumor model studies indicate that XERECEPT® also has antitumor activity."
The results from NTI-0303, a Phase III multi-center, placebo-controlled, randomized clinical study conducted at more than 25 sites in the US and Canada, showed that XERECEPT® enabled substantial decreases in steroid usage and its associated side effects in both acute and long-term treatment of patients with edema associated with either primary or metastatic brain tumors.
The primary endpoint of this study was a composite of three factors during weeks two through five: a 50 percent reduction in dexamethasone, stable or improved Karnofsky performance status and stable or improved 10-item Neurological Examination Scores.
On the primary endpoint (during weeks two through five of treatment), the study demonstrated a strong trend in favor of XERECEPT®, though it did not reach statistical significance (p=0.1). Placebo patients tolerated a 50 percent reduction in dexamethasone dosing much better than anticipated over this time frame.
However, at weeks two, five, and eight, the XERECEPT® treatment group demonstrated an improved overall response rate based on the primary endpoint that was statistically significant at each time point. XERECEPT® demonstrated a highly statistically significant improvement compared to placebo over the twelve weeks of study duration in reducing dexamethasone dose levels. Fifteen percent of patients on XERECEPT® were able to reach 0 mg of dexamethasone (p= 0.04) within the twelve week period.
Approximately 20 percent of the patients enrolled in NTI-0303 had metastatic brain tumors (secondary to primary tumors in the breast, lung or elsewhere). In this patient population, the primary and all secondary endpoints achieved a statistically significant advantage for XERECEPT® treated patients, exceeding the results observed in the overall patient cohort. This is an important finding given the 360,000 patients diagnosed annually with metastatic brain tumors in North America and Europe; moreover, patient prognosis is very poor and the treatment options are very limited.
In addition, the NTI-0303 trial showed that use of XERECEPT® leads to statistically significant reductions in steroid-related adverse events of myopathy (muscle weakness) and Cushingoid syndrome. Specifically, patients demonstrated a statistically significant increase in Ileopsoas muscle strength. These findings show a medically important clinical benefit for patients on XERECEPT®.
NTI-0501 Results from NTI-0501, a Phase III open label extension study of patients rolling over from the 0302 and 0303 studies, demonstrated the long-term tolerability of XERECEPT®. Of the 113 patients enrolled, a total of 32 patients have completed one year or more of treatment in the study. Dexamethasone dosing of all patients on study was reduced progressively over time.
Celtic Pharma believes these studies demonstrate that XERECEPT® was well tolerated and enabled clinically significant reductions in corticosteroid use in patients with cerebral edema associated with both primary and metastatic brain tumors. The Company also announced the results of several preclinical studies demonstrating potential anti-tumor and angiogenesis inhibition effects of XERECEPT®.
"The ability to reduce the use of steroids and concomitant reduction in adverse side effects in the treatment of patients with brain tumors is an important goal,” said Lawrence Recht, MD, Professor of Neurology and Neurological Sciences, Stanford University Medical Center.
“The results of these late-stage studies are encouraging, both in terms of lowering dexamethasone use over the longer-term and the impact seen in metastatic patients, a large group with limited treatment options. The preclinical tumor model studies indicate that XERECEPT® also has antitumor activity."
The results from NTI-0303, a Phase III multi-center, placebo-controlled, randomized clinical study conducted at more than 25 sites in the US and Canada, showed that XERECEPT® enabled substantial decreases in steroid usage and its associated side effects in both acute and long-term treatment of patients with edema associated with either primary or metastatic brain tumors.
The primary endpoint of this study was a composite of three factors during weeks two through five: a 50 percent reduction in dexamethasone, stable or improved Karnofsky performance status and stable or improved 10-item Neurological Examination Scores.
On the primary endpoint (during weeks two through five of treatment), the study demonstrated a strong trend in favor of XERECEPT®, though it did not reach statistical significance (p=0.1). Placebo patients tolerated a 50 percent reduction in dexamethasone dosing much better than anticipated over this time frame.
However, at weeks two, five, and eight, the XERECEPT® treatment group demonstrated an improved overall response rate based on the primary endpoint that was statistically significant at each time point. XERECEPT® demonstrated a highly statistically significant improvement compared to placebo over the twelve weeks of study duration in reducing dexamethasone dose levels. Fifteen percent of patients on XERECEPT® were able to reach 0 mg of dexamethasone (p= 0.04) within the twelve week period.
Approximately 20 percent of the patients enrolled in NTI-0303 had metastatic brain tumors (secondary to primary tumors in the breast, lung or elsewhere). In this patient population, the primary and all secondary endpoints achieved a statistically significant advantage for XERECEPT® treated patients, exceeding the results observed in the overall patient cohort. This is an important finding given the 360,000 patients diagnosed annually with metastatic brain tumors in North America and Europe; moreover, patient prognosis is very poor and the treatment options are very limited.
In addition, the NTI-0303 trial showed that use of XERECEPT® leads to statistically significant reductions in steroid-related adverse events of myopathy (muscle weakness) and Cushingoid syndrome. Specifically, patients demonstrated a statistically significant increase in Ileopsoas muscle strength. These findings show a medically important clinical benefit for patients on XERECEPT®.
NTI-0501 Results from NTI-0501, a Phase III open label extension study of patients rolling over from the 0302 and 0303 studies, demonstrated the long-term tolerability of XERECEPT®. Of the 113 patients enrolled, a total of 32 patients have completed one year or more of treatment in the study. Dexamethasone dosing of all patients on study was reduced progressively over time.
