New B-Cell Depleting Agent Is Well Tolerated : TRU-015 resulted in ACR20 improvement in half of 36 patients studied; 25% had ACR50 responses.

PARIS — Repeated treatment with a new type of B-cell-depleting agent was well tolerated and reduced signs and symptoms of rheumatoid arthritis, according to an interim analysis of an ongoing open-label study.

Analysis of pooled clinical responses from two dosage groups found that approximately 50% of patients achieved a 20% improvement in American College of Rheumatology parameters (ACR20); 25% had ACR50 responses, and 10%–15% had ACR70 responses, Dr. Richard W. Martin said at the annual European Congress of Rheumatology.

TRU-015 is a small modular immunopharmaceutical (SMIP), a single-chain protein that is approximately one-half to one-third the size of a monoclonal antibody. It is directed against CD20 markers on the surfaces of B cells, Dr. Martin said.

TRU-015 differs from rituximab in that it is human rather than chimeric, and was designed using a custom drug assembly technology that reduces complement activation, which is thought to contribute to some rituximab-associated adverse events, such as infusion reactions, and may play a role in disease activity in RA.

In all, 36 patients have now had at least one retreatment (that is, a second infusion), and 29 have had more than one retreatment (at least three infusions).

At this point, more than 100 courses of the experimental agent have been administered, with some patients receiving up to six courses over 3 years, Dr. Martin said. Patients who had previously received an infusion of at least 5 mg/kg and who completed 24 weeks of follow-up with at least 70% of B-cell recovery were eligible for retreatment with either 5 mg/kg or 15 mg/kg of TRU-015.

The infusions have generally been well tolerated, and there have been no grade 3 or 4 adverse events. Four patients had grade 2 adverse events, including facial flushing, erythema, and pruritus, as well as worsening insomnia.

Whether these events were caused by the study agent or by pretreatment with corticosteroids is not known, said Dr. Martin, professor of medicine and rheumatology at Michigan State University, Grand Rapids.

Six patients withdrew from the study, primarily for administrative reasons. There were no withdrawals because of adverse events, and there have been no opportunistic infections or deaths.

Headache was reported by 28% of patients after their first infusion; this fell to 8% and 7% after the second and third infusions. Other adverse events, such as fatigue and edema, also decreased with repeated treatments.

Nine serious adverse events were seen in seven patients. One patient had two hospitalizations for exacerbations of chronic obstructive pulmonary disease, another patient experienced an episode of cholecystitis, and one reported shortness of breath of unknown cause.

The retreatment pharmacokinetics of TRU-015 following repeated infusions are indistinguishable from those seen with the initial treatment, suggesting that there is no significant early development of neutralizing antibodies. There also was no attenuation in B-cell depletion following retreatment.

Clinical responses have been maintained from the first treatment to the second and beyond, he added.

Dr. Martin did not say when the trial was expected to be complete.

The manufacturer of TRU-015, Trubion Pharmaceuticals Inc., is creating a pipeline of customized therapeutic products, including SMIPs, for the treatment of autoimmune and inflammatory diseases and cancer.

Additionally, Wyeth Pharmaceuticals and Trubion have a worldwide licensing and commercialization agreement for the development of TRU-015 and other CD20-targeted therapies.

Dr. Martin disclosed that he has had contracts for clinical trials with Trubion, but owns no stock in the company and is not a paid consultant.

PARIS — Repeated treatment with a new type of B-cell-depleting agent was well tolerated and reduced signs and symptoms of rheumatoid arthritis, according to an interim analysis of an ongoing open-label study.

Analysis of pooled clinical responses from two dosage groups found that approximately 50% of patients achieved a 20% improvement in American College of Rheumatology parameters (ACR20); 25% had ACR50 responses, and 10%–15% had ACR70 responses, Dr. Richard W. Martin said at the annual European Congress of Rheumatology.

TRU-015 is a small modular immunopharmaceutical (SMIP), a single-chain protein that is approximately one-half to one-third the size of a monoclonal antibody. It is directed against CD20 markers on the surfaces of B cells, Dr. Martin said.

TRU-015 differs from rituximab in that it is human rather than chimeric, and was designed using a custom drug assembly technology that reduces complement activation, which is thought to contribute to some rituximab-associated adverse events, such as infusion reactions, and may play a role in disease activity in RA.

In all, 36 patients have now had at least one retreatment (that is, a second infusion), and 29 have had more than one retreatment (at least three infusions).

At this point, more than 100 courses of the experimental agent have been administered, with some patients receiving up to six courses over 3 years, Dr. Martin said. Patients who had previously received an infusion of at least 5 mg/kg and who completed 24 weeks of follow-up with at least 70% of B-cell recovery were eligible for retreatment with either 5 mg/kg or 15 mg/kg of TRU-015.

The infusions have generally been well tolerated, and there have been no grade 3 or 4 adverse events. Four patients had grade 2 adverse events, including facial flushing, erythema, and pruritus, as well as worsening insomnia.

Whether these events were caused by the study agent or by pretreatment with corticosteroids is not known, said Dr. Martin, professor of medicine and rheumatology at Michigan State University, Grand Rapids.

Six patients withdrew from the study, primarily for administrative reasons. There were no withdrawals because of adverse events, and there have been no opportunistic infections or deaths.

Headache was reported by 28% of patients after their first infusion; this fell to 8% and 7% after the second and third infusions. Other adverse events, such as fatigue and edema, also decreased with repeated treatments.

Nine serious adverse events were seen in seven patients. One patient had two hospitalizations for exacerbations of chronic obstructive pulmonary disease, another patient experienced an episode of cholecystitis, and one reported shortness of breath of unknown cause.

The retreatment pharmacokinetics of TRU-015 following repeated infusions are indistinguishable from those seen with the initial treatment, suggesting that there is no significant early development of neutralizing antibodies. There also was no attenuation in B-cell depletion following retreatment.

Clinical responses have been maintained from the first treatment to the second and beyond, he added.

Dr. Martin did not say when the trial was expected to be complete.

The manufacturer of TRU-015, Trubion Pharmaceuticals Inc., is creating a pipeline of customized therapeutic products, including SMIPs, for the treatment of autoimmune and inflammatory diseases and cancer.

Additionally, Wyeth Pharmaceuticals and Trubion have a worldwide licensing and commercialization agreement for the development of TRU-015 and other CD20-targeted therapies.

Dr. Martin disclosed that he has had contracts for clinical trials with Trubion, but owns no stock in the company and is not a paid consultant.

PARIS — Repeated treatment with a new type of B-cell-depleting agent was well tolerated and reduced signs and symptoms of rheumatoid arthritis, according to an interim analysis of an ongoing open-label study.

Analysis of pooled clinical responses from two dosage groups found that approximately 50% of patients achieved a 20% improvement in American College of Rheumatology parameters (ACR20); 25% had ACR50 responses, and 10%–15% had ACR70 responses, Dr. Richard W. Martin said at the annual European Congress of Rheumatology.

TRU-015 is a small modular immunopharmaceutical (SMIP), a single-chain protein that is approximately one-half to one-third the size of a monoclonal antibody. It is directed against CD20 markers on the surfaces of B cells, Dr. Martin said.

TRU-015 differs from rituximab in that it is human rather than chimeric, and was designed using a custom drug assembly technology that reduces complement activation, which is thought to contribute to some rituximab-associated adverse events, such as infusion reactions, and may play a role in disease activity in RA.

In all, 36 patients have now had at least one retreatment (that is, a second infusion), and 29 have had more than one retreatment (at least three infusions).

At this point, more than 100 courses of the experimental agent have been administered, with some patients receiving up to six courses over 3 years, Dr. Martin said. Patients who had previously received an infusion of at least 5 mg/kg and who completed 24 weeks of follow-up with at least 70% of B-cell recovery were eligible for retreatment with either 5 mg/kg or 15 mg/kg of TRU-015.

The infusions have generally been well tolerated, and there have been no grade 3 or 4 adverse events. Four patients had grade 2 adverse events, including facial flushing, erythema, and pruritus, as well as worsening insomnia.

Whether these events were caused by the study agent or by pretreatment with corticosteroids is not known, said Dr. Martin, professor of medicine and rheumatology at Michigan State University, Grand Rapids.

Six patients withdrew from the study, primarily for administrative reasons. There were no withdrawals because of adverse events, and there have been no opportunistic infections or deaths.

Headache was reported by 28% of patients after their first infusion; this fell to 8% and 7% after the second and third infusions. Other adverse events, such as fatigue and edema, also decreased with repeated treatments.

Nine serious adverse events were seen in seven patients. One patient had two hospitalizations for exacerbations of chronic obstructive pulmonary disease, another patient experienced an episode of cholecystitis, and one reported shortness of breath of unknown cause.

The retreatment pharmacokinetics of TRU-015 following repeated infusions are indistinguishable from those seen with the initial treatment, suggesting that there is no significant early development of neutralizing antibodies. There also was no attenuation in B-cell depletion following retreatment.

Clinical responses have been maintained from the first treatment to the second and beyond, he added.

Dr. Martin did not say when the trial was expected to be complete.

The manufacturer of TRU-015, Trubion Pharmaceuticals Inc., is creating a pipeline of customized therapeutic products, including SMIPs, for the treatment of autoimmune and inflammatory diseases and cancer.

Additionally, Wyeth Pharmaceuticals and Trubion have a worldwide licensing and commercialization agreement for the development of TRU-015 and other CD20-targeted therapies.

Dr. Martin disclosed that he has had contracts for clinical trials with Trubion, but owns no stock in the company and is not a paid consultant.