PHILLIPSBURG, NJ, USA I July 1, 2013 I Celldex Therapeutics, Inc. (CLDX) today reported that the first patient has been dosed in the Company‘s pilot study of CDX-1135 (a soluble form of human complement receptor type 1) in dense deposit disease (DDD). DDD is an ultra-rare, progressive kidney disease that ultimately results in kidney failure in the majority of affected individuals. DDD is caused by dysregulation of the C3 Convertase, a major early component of the alternative pathway of complement. CDX-1135 has been shown to inhibit complement activation and has yielded promising results in an animal model of DDD and in a single patient with DDD that was treated under a compassionate use protocol.
The open-label study will enroll up to five patients (ages four and older) from clinical centers across the United States to determine the CDX-1135 dose level required to normalize alternative complement activity on an individual patient basis. Potential effects on renal function will also be assessed. Patients will initially be treated at the University of Iowa under the leadership of Richard J.H. Smith, MD and Carla M. Nester, MD. If selected complement levels normalize on therapy, patients may be able to return to their local treatment center to continue in the study. Dr. Smith, a widely recognized expert in DDD, is Professor of Otolaryngology and Internal Medicine and the Director of the Molecular Otolaryngology and Renal Research Laboratories (MORL) at the University of Iowa. MORL maintains the largest DDD patient database in the world. Dr. Nester, also a member of MORL, is an Assistant Professor at the University of Iowa, trained in adult and pediatric nephrology.
“CDX-1135 is a much needed and exciting entrant to the dense deposit disease field,” said Dr. Smith. “There are currently no treatments and nearly half of all patients progress to end-stage renal disease within 10 years of presentation, often spending the rest of their lives on dialysis. In a mouse model of dense deposit disease, CDX-1135 has been shown to control the abnormal complement activity and to reduce deposits in the kidneys. Short term use of CDX-1135 in a patient with dense deposit disease and end-stage renal disease was well-tolerated and normalized the activity of the alternative complement pathway. We are optimistic that if we can control complement activation earlier in the disease course and at a critical step in the complement pathway, CDX-1135 may be able to restore kidney function and provide long term disease control—a long-awaited outcome for patients, their families and physicians.”
Dr. Thomas Davis, Chief Medical Officer of Celldex, added, “Based on research to date in dense deposit disease and other indications, we believe CDX-1135 has the potential to play an important role in complement mediated diseases, uniquely in indications where the C3 Convertase is very active leading to a consumption of C3 and deposition of harmful breakdown products onto the kidney. We look forward to completing this study in dense deposit disease and, with positive results, given the unmet need for these patients, we will seek to expand the CDX-1135 program into a larger study in dense deposit disease as quickly as possible.”
About Dense Deposit Disease:
Dense Deposit Disease (DDD) is a rare kidney disease affecting two persons per million. DDD is caused by uncontrolled activation of the alternative pathway of complement, which leads to the consumption of the circulating complement component C3, deposition of C3 and other proteins in the kidneys, and subsequent damage to kidney function. Approximately 50% of patients with dense deposit disease progress to end stage renal disease (ESRD) within 10 years of diagnosis. Patients diagnosed at a younger age (≤ 12 years old) are more likely to progress to ESRD and progress more rapidly (typically within 4 years). Kidney transplantation is not a viable option because DDD recurs in virtually all patients who receive a transplant. There are no treatments at this time for DDD.
About CDX-1135:
CDX-1135 is soluble complement receptor type 1 (sCR1), a recombinant human protein made in mammalian cell cultures that is a potent inhibitor of complement activation, including the classical, lectin and alternative complement pathways, both at the early (C3) and late (C5) activation steps in these pathways. Previous clinical studies of CDX-1135 in more than 500 patients in other indications have suggested that CDX-1135 has a favorable safety profile and is a potent inhibitor of the complement pathway. In dense deposit disease, CDX-1135 has been shown to control the activation of alternative pathway complement in patient serum samples in vitro. In a mouse model of DDD, the administration of CDX-1135 was shown to control complement activation in vivo, preventing the damaging deposition of C3 in the kidneys. Short term compassionate use of CDX-1135 in a patient with DDD also showed control of complement abnormalities. This patient was already in renal failure requiring dialysis and so reversal of disease was not expected. The newly initiated pilot study is exploring the potential for clinical benefit in patients with earlier stage DDD, where C3 consumption and deposition play an important role in disease progression, and where the greatest potential to restore kidney function and provide long term disease control exists.
About Celldex Therapeutics, Inc.:
Celldex is developing targeted therapeutics to address devastating diseases for which available treatments are inadequate. Our pipeline is built from a proprietary portfolio of antibodies and immunomodulators used alone and in strategic combinations to create novel, disease-specific therapies that induce, enhance or suppress the body’s immune response. Visit http://www.celldextherapeutics.com.
SOURCE: Celldex Therapeutics
Post Views: 30
PHILLIPSBURG, NJ, USA I July 1, 2013 I Celldex Therapeutics, Inc. (CLDX) today reported that the first patient has been dosed in the Company‘s pilot study of CDX-1135 (a soluble form of human complement receptor type 1) in dense deposit disease (DDD). DDD is an ultra-rare, progressive kidney disease that ultimately results in kidney failure in the majority of affected individuals. DDD is caused by dysregulation of the C3 Convertase, a major early component of the alternative pathway of complement. CDX-1135 has been shown to inhibit complement activation and has yielded promising results in an animal model of DDD and in a single patient with DDD that was treated under a compassionate use protocol.
The open-label study will enroll up to five patients (ages four and older) from clinical centers across the United States to determine the CDX-1135 dose level required to normalize alternative complement activity on an individual patient basis. Potential effects on renal function will also be assessed. Patients will initially be treated at the University of Iowa under the leadership of Richard J.H. Smith, MD and Carla M. Nester, MD. If selected complement levels normalize on therapy, patients may be able to return to their local treatment center to continue in the study. Dr. Smith, a widely recognized expert in DDD, is Professor of Otolaryngology and Internal Medicine and the Director of the Molecular Otolaryngology and Renal Research Laboratories (MORL) at the University of Iowa. MORL maintains the largest DDD patient database in the world. Dr. Nester, also a member of MORL, is an Assistant Professor at the University of Iowa, trained in adult and pediatric nephrology.
“CDX-1135 is a much needed and exciting entrant to the dense deposit disease field,” said Dr. Smith. “There are currently no treatments and nearly half of all patients progress to end-stage renal disease within 10 years of presentation, often spending the rest of their lives on dialysis. In a mouse model of dense deposit disease, CDX-1135 has been shown to control the abnormal complement activity and to reduce deposits in the kidneys. Short term use of CDX-1135 in a patient with dense deposit disease and end-stage renal disease was well-tolerated and normalized the activity of the alternative complement pathway. We are optimistic that if we can control complement activation earlier in the disease course and at a critical step in the complement pathway, CDX-1135 may be able to restore kidney function and provide long term disease control—a long-awaited outcome for patients, their families and physicians.”
Dr. Thomas Davis, Chief Medical Officer of Celldex, added, “Based on research to date in dense deposit disease and other indications, we believe CDX-1135 has the potential to play an important role in complement mediated diseases, uniquely in indications where the C3 Convertase is very active leading to a consumption of C3 and deposition of harmful breakdown products onto the kidney. We look forward to completing this study in dense deposit disease and, with positive results, given the unmet need for these patients, we will seek to expand the CDX-1135 program into a larger study in dense deposit disease as quickly as possible.”
About Dense Deposit Disease:
Dense Deposit Disease (DDD) is a rare kidney disease affecting two persons per million. DDD is caused by uncontrolled activation of the alternative pathway of complement, which leads to the consumption of the circulating complement component C3, deposition of C3 and other proteins in the kidneys, and subsequent damage to kidney function. Approximately 50% of patients with dense deposit disease progress to end stage renal disease (ESRD) within 10 years of diagnosis. Patients diagnosed at a younger age (≤ 12 years old) are more likely to progress to ESRD and progress more rapidly (typically within 4 years). Kidney transplantation is not a viable option because DDD recurs in virtually all patients who receive a transplant. There are no treatments at this time for DDD.
About CDX-1135:
CDX-1135 is soluble complement receptor type 1 (sCR1), a recombinant human protein made in mammalian cell cultures that is a potent inhibitor of complement activation, including the classical, lectin and alternative complement pathways, both at the early (C3) and late (C5) activation steps in these pathways. Previous clinical studies of CDX-1135 in more than 500 patients in other indications have suggested that CDX-1135 has a favorable safety profile and is a potent inhibitor of the complement pathway. In dense deposit disease, CDX-1135 has been shown to control the activation of alternative pathway complement in patient serum samples in vitro. In a mouse model of DDD, the administration of CDX-1135 was shown to control complement activation in vivo, preventing the damaging deposition of C3 in the kidneys. Short term compassionate use of CDX-1135 in a patient with DDD also showed control of complement abnormalities. This patient was already in renal failure requiring dialysis and so reversal of disease was not expected. The newly initiated pilot study is exploring the potential for clinical benefit in patients with earlier stage DDD, where C3 consumption and deposition play an important role in disease progression, and where the greatest potential to restore kidney function and provide long term disease control exists.
About Celldex Therapeutics, Inc.:
Celldex is developing targeted therapeutics to address devastating diseases for which available treatments are inadequate. Our pipeline is built from a proprietary portfolio of antibodies and immunomodulators used alone and in strategic combinations to create novel, disease-specific therapies that induce, enhance or suppress the body’s immune response. Visit http://www.celldextherapeutics.com.
SOURCE: Celldex Therapeutics
Post Views: 30
