Data from New Drug Trial Offers Prospect for Enhanced Quality of Life for Children with Late Stage Brain Tumors

Results of Phase I/II study of Xerecept® in Pediatric Patients with Peritumoral Cerebral Edema presented at International Symposium for Pediatric Neuro-Oncology in Toronto, Canada

Key Points

• Phase I/II data from a 15 patient study shows Xerecept® is safe and can reduce or eliminate the need for steroids in pediatric patients with cerebral tumors, thus reducing or eliminating debilitating steroid-associated side effects, while yielding significant quality of life improvements

• Patients dosed with Xerecept® showed that 35% of patients able to completely cease using steroids and 70% decreased their steroids by 50%, despite progressive disease in all patients

• Xerecept® has been administered to over 400 patients in the course of its clinical development and is in Phase III development for adults with brain tumors

• An end of Phase II meeting has already been held with the FDA to discuss the pathway for a pivotal trial towards registration of Xerecept® in this pediatric indication

 

Bermuda, London and New York, June 27, 2012 – Data presented today by Dr. Stewart Goldman M.D of the Children’s Memorial Hospital, Chicago at the International Symposium for Pediatric Neuro-Oncology being held in Toronto, Canada showed encouraging positive results from a Phase I/II study of Xerecept in Pediatric Patients with Peritumoral Cerebral Edema (brain tumors).

Xerecept® is an investigational new drug for use in pediatric patients who are dependent on the steroid Decadron (dexamethasone) to treat peritumoral brain edema associated with cerebral tumors. Approximately 4,000 cases of pediatric brain tumors are diagnosed each year in the United States. Data from this Phase I/II study showed that Xerecept® was safe and well tolerated at all doses levels in these patients. Initial indications are that the drug can reduce or eliminate the need for Decadron, and the steroid-associated side effects, providing significant quality of life improvements.

The latest study, involving 15 children, was conducted by Stewart Goldman M.D. at Children's Memorial Hospital in Chicago, IL and Mark Kieran M.D. at Dana-Farber Cancer Institute in Boston, MA. All of the children enrolled on the study had severe steroid-induced side effects and had been unable to decrease dexamethasone dosing in spite of two attempts to do so by the attending physicians.

Corticosteroids (predominantly dexamethasone), the current standard treatment of peritumoral brain edema associated with cerebral tumors, have severe side effects such as severe myopathies, muscle wasting, morbid weight gain, osteoporosis, gastritis, gastrointestinal bleeding, hypertension and personality changes. These side effects are accentuated in pediatric patients, with substantial impact on the patient’s ability to function in daily life.

“For those of us who treat children with brain tumors in our daily practice, the prospect of a safe and effective alternative to corticosteroids to control edema in these patients is indeed exciting”, said Dr. Stewart Goldman, Children’s Memorial in Chicago.

Of the 14 evaluable patients, all were able to reduce dexamethasone usage including 10 who reduced their dose by more than 50%, and five of the 10 were able to completely cease using steroids. 88% of patients on Xerecept® for at least six weeks reduced dexamethasone to less than 1mg. Those patients treated with Xerecept® at the daily maximum dose of 60µg/kg/day for longer than six weeks stopped decadron completely for over twelve weeks on average. These reductions in steroid dosing occurred despite progressive disease in all patients.

Xerecept® dosing not only had positive effects on the steroid-associated side effects, but was also associated with significant improvements in physical and emotional functioning and fatigue, as measured by use of the PedsQL™, a quality of life instrument which has been validated for use in pediatric patients with cerebral tumors.

The PedsQL™ Measurement Model comprises a validated tool of developmentally appropriate generic core scales and disease-specific modules that measure quality of life for children and adolescents. While their dexamethasone dose was being reduced, a defined cohort of the evaluable patients improved their sleep/rest and total fatigue scores such that by Week 18 their status was comparable to healthy children. Similar compelling changes were seen for emotional functioning; at baseline patients tested at a level comparable to pediatric patients with chronic psychiatric disease but scores improved during the study and by Week 22 patients again tested similarly to a healthy population.

There was a consistent improvement in social and physical functioning and other measures indicative of how a patient feels and functions. These improvements, together with the overall reduction in steroid usage, were impressive as they occurred against the background of tumor progression that is normally expected to negatively impact quality of life and require increased dexamethasone dosing.

The study demonstrated that Xerecept® is safe at daily doses of 60µg/kg/day administered subcutaneously twice daily in divided doses with no Dose Limiting Toxicities and no reported drug related Grade III or IV toxicities. No clinically significant Xerecept® drug-related side effects were observed in any of the patients.

The development of Xerecept® (corticorelin acetate) is being funded by Celtic Pharmaceutical Holdings L.P. (“Celtic Pharma”), a global private equity firm focused on late stage pharmaceutical assets. Xerecept® is already in Phase III development for the treatment of cerebral edema associated with primary and metastatic brain tumors in adults.

Dr. O'Connor, head of clinical development for Celtic Pharma, stated: “It is exciting to observe that dosing with Xerecept® is associated with sharply decreased or eliminated use of dexamethasone in pediatric patients. In this study, all of the key stakeholders including patients, parents and investigators were impressed with the study outcome and supported further development of Xerecept® for a pediatric indication.”

Subsequent to completion of the study, Celtic Pharma has held an end of Phase II meeting with the FDA’s Oncology Division, to discuss the pathway for registration of Xerecept® in this pediatric indication and the appropriate primary end-point for a follow on pivotal study. The FDA has provided guidance on these points, and it was agreed that Celtic Pharma would submit a detailed protocol for a pivotal study in pediatric patients for review by the Agency in the near future.

“Xerecept clearly has the potential to significantly improve the quality of life for children with brain tumors for as long as they are able to survive the underlying disease” said Stephen Evans-Freke, Managing General Partner of Celtic Pharma. “We remain committed to doing whatever we can to accelerate bringing the benefits of Xerecept to clinical care of pediatric brain tumor patients, and all patients with primary and metastatic brain tumors.”

About Xerecept®

Xerecept® is a synthetic version of the natural peptide hormone ‘corticotrophin releasing factor’. Xerecept® is in Phase III development for the treatment of cerebral edema associated with primary and metastatic brain tumors in adults, and has been demonstrated in prior trials to be an effective alternative to the use of chronic, high-dose corticosteroids in this large patient population, while offering a benign side-effect profile even over several years of chronic administration. Recent preclinical studies from leading cancer centers have indicated that Xerecept® may also have direct anti-tumor effects, and may be synergistic with Avastin in certain solid tumors.

About Celtic Pharmaceutical Holdings L.P.

Celtic Pharmaceutical Holdings L.P. (Celtic Pharma) is a global private equity investment firm focused on the biotechnology and pharmaceutical industries. Celtic Pharma was founded by Stephen Evans-Freke and John Mayo, CBE and is based in Bermuda, with offices in New York and London. Celtic Pharma has acquired and invested in late stage pharmaceutical programs and manages these programs through their development for ultimate sale to established pharmaceutical companies. Celtic Pharma is fully invested at this time. Celtic Pharma’s aim has b

Results of Phase I/II study of Xerecept® in Pediatric Patients with Peritumoral Cerebral Edema presented at International Symposium for Pediatric Neuro-Oncology in Toronto, Canada

Key Points

• Phase I/II data from a 15 patient study shows Xerecept® is safe and can reduce or eliminate the need for steroids in pediatric patients with cerebral tumors, thus reducing or eliminating debilitating steroid-associated side effects, while yielding significant quality of life improvements

• Patients dosed with Xerecept® showed that 35% of patients able to completely cease using steroids and 70% decreased their steroids by 50%, despite progressive disease in all patients

• Xerecept® has been administered to over 400 patients in the course of its clinical development and is in Phase III development for adults with brain tumors

• An end of Phase II meeting has already been held with the FDA to discuss the pathway for a pivotal trial towards registration of Xerecept® in this pediatric indication

 

Bermuda, London and New York, June 27, 2012 – Data presented today by Dr. Stewart Goldman M.D of the Children’s Memorial Hospital, Chicago at the International Symposium for Pediatric Neuro-Oncology being held in Toronto, Canada showed encouraging positive results from a Phase I/II study of Xerecept in Pediatric Patients with Peritumoral Cerebral Edema (brain tumors).

Xerecept® is an investigational new drug for use in pediatric patients who are dependent on the steroid Decadron (dexamethasone) to treat peritumoral brain edema associated with cerebral tumors. Approximately 4,000 cases of pediatric brain tumors are diagnosed each year in the United States. Data from this Phase I/II study showed that Xerecept® was safe and well tolerated at all doses levels in these patients. Initial indications are that the drug can reduce or eliminate the need for Decadron, and the steroid-associated side effects, providing significant quality of life improvements.

The latest study, involving 15 children, was conducted by Stewart Goldman M.D. at Children's Memorial Hospital in Chicago, IL and Mark Kieran M.D. at Dana-Farber Cancer Institute in Boston, MA. All of the children enrolled on the study had severe steroid-induced side effects and had been unable to decrease dexamethasone dosing in spite of two attempts to do so by the attending physicians.

Corticosteroids (predominantly dexamethasone), the current standard treatment of peritumoral brain edema associated with cerebral tumors, have severe side effects such as severe myopathies, muscle wasting, morbid weight gain, osteoporosis, gastritis, gastrointestinal bleeding, hypertension and personality changes. These side effects are accentuated in pediatric patients, with substantial impact on the patient’s ability to function in daily life.

“For those of us who treat children with brain tumors in our daily practice, the prospect of a safe and effective alternative to corticosteroids to control edema in these patients is indeed exciting”, said Dr. Stewart Goldman, Children’s Memorial in Chicago.

Of the 14 evaluable patients, all were able to reduce dexamethasone usage including 10 who reduced their dose by more than 50%, and five of the 10 were able to completely cease using steroids. 88% of patients on Xerecept® for at least six weeks reduced dexamethasone to less than 1mg. Those patients treated with Xerecept® at the daily maximum dose of 60µg/kg/day for longer than six weeks stopped decadron completely for over twelve weeks on average. These reductions in steroid dosing occurred despite progressive disease in all patients.

Xerecept® dosing not only had positive effects on the steroid-associated side effects, but was also associated with significant improvements in physical and emotional functioning and fatigue, as measured by use of the PedsQL™, a quality of life instrument which has been validated for use in pediatric patients with cerebral tumors.

The PedsQL™ Measurement Model comprises a validated tool of developmentally appropriate generic core scales and disease-specific modules that measure quality of life for children and adolescents. While their dexamethasone dose was being reduced, a defined cohort of the evaluable patients improved their sleep/rest and total fatigue scores such that by Week 18 their status was comparable to healthy children. Similar compelling changes were seen for emotional functioning; at baseline patients tested at a level comparable to pediatric patients with chronic psychiatric disease but scores improved during the study and by Week 22 patients again tested similarly to a healthy population.

There was a consistent improvement in social and physical functioning and other measures indicative of how a patient feels and functions. These improvements, together with the overall reduction in steroid usage, were impressive as they occurred against the background of tumor progression that is normally expected to negatively impact quality of life and require increased dexamethasone dosing.

The study demonstrated that Xerecept® is safe at daily doses of 60µg/kg/day administered subcutaneously twice daily in divided doses with no Dose Limiting Toxicities and no reported drug related Grade III or IV toxicities. No clinically significant Xerecept® drug-related side effects were observed in any of the patients.

The development of Xerecept® (corticorelin acetate) is being funded by Celtic Pharmaceutical Holdings L.P. (“Celtic Pharma”), a global private equity firm focused on late stage pharmaceutical assets. Xerecept® is already in Phase III development for the treatment of cerebral edema associated with primary and metastatic brain tumors in adults.

Dr. O'Connor, head of clinical development for Celtic Pharma, stated: “It is exciting to observe that dosing with Xerecept® is associated with sharply decreased or eliminated use of dexamethasone in pediatric patients. In this study, all of the key stakeholders including patients, parents and investigators were impressed with the study outcome and supported further development of Xerecept® for a pediatric indication.”

Subsequent to completion of the study, Celtic Pharma has held an end of Phase II meeting with the FDA’s Oncology Division, to discuss the pathway for registration of Xerecept® in this pediatric indication and the appropriate primary end-point for a follow on pivotal study. The FDA has provided guidance on these points, and it was agreed that Celtic Pharma would submit a detailed protocol for a pivotal study in pediatric patients for review by the Agency in the near future.

“Xerecept clearly has the potential to significantly improve the quality of life for children with brain tumors for as long as they are able to survive the underlying disease” said Stephen Evans-Freke, Managing General Partner of Celtic Pharma. “We remain committed to doing whatever we can to accelerate bringing the benefits of Xerecept to clinical care of pediatric brain tumor patients, and all patients with primary and metastatic brain tumors.”

About Xerecept®

Xerecept® is a synthetic version of the natural peptide hormone ‘corticotrophin releasing factor’. Xerecept® is in Phase III development for the treatment of cerebral edema associated with primary and metastatic brain tumors in adults, and has been demonstrated in prior trials to be an effective alternative to the use of chronic, high-dose corticosteroids in this large patient population, while offering a benign side-effect profile even over several years of chronic administration. Recent preclinical studies from leading cancer centers have indicated that Xerecept® may also have direct anti-tumor effects, and may be synergistic with Avastin in certain solid tumors.

About Celtic Pharmaceutical Holdings L.P.

Celtic Pharmaceutical Holdings L.P. (Celtic Pharma) is a global private equity investment firm focused on the biotechnology and pharmaceutical industries. Celtic Pharma was founded by Stephen Evans-Freke and John Mayo, CBE and is based in Bermuda, with offices in New York and London. Celtic Pharma has acquired and invested in late stage pharmaceutical programs and manages these programs through their development for ultimate sale to established pharmaceutical companies. Celtic Pharma is fully invested at this time. Celtic Pharma’s aim has been to bridge the gap between the established pharmaceutical companies’ new product pipeline crisis and the biotech industry’s capital drought. For further information, please visit Celtic Pharma’s website at www.celticpharma.com.

ENQUIRIES

Media Relations

College Hill Life Sciences

Rebecca Skye Dietrich (US): +1 857 241 0795

Sue Charles/Gemma Howe/Rebecca Caygill: +44 (0)20 7866 7863

celtic@collegehill.com

At the Company

Celtic Pharma Management L.P.

Investor Relations

Ms. Kathy Armstrong: +1 (212) 616 4042

kathy@celticpharma.com

 

een to bridge the gap between the established pharmaceutical companies’ new product pipeline crisis and the biotech industry’s capital drought. For further information, please visit Celtic Pharma’s website at www.celticpharma.com.

ENQUIRIES

Media Relations

College Hill Life Sciences

Rebecca Skye Dietrich (US): +1 857 241 0795

Sue Charles/Gemma Howe/Rebecca Caygill: +44 (0)20 7866 7863

celtic@collegehill.com

At the Company

Celtic Pharma Management L.P.

Investor Relations

Ms. Kathy Armstrong: +1 (212) 616 4042

kathy@celticpharma.com

 

Posted: June 2012

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