Pharma Live
Swedish drug development company OxyPharma today announced the preliminary results of its phase II clinical trial of Rabeximod, an orally administered disease-modifying anti-rheumatic drug (DMARD) for treatment of moderate or severe active rheumatoid arthritis. The study demonstrated clear therapeutic effects of Rabeximod in patients with rheumatoid arthritis, resulting in a significant effect on key biological and disease variables after 16 weeks.
The study was designed to reveal an effect of Rabeximod at 12 weeks (primary endpoint), based on the assumption of a similar onset of action as other disease-modifying anti-rheumatic drugs. Treatment with Rabeximod was given during 12 weeks to 224 patients with moderate or severe active rheumatoid arthritis that were not fully responsive to prior treatment withmethotrexate , with clinical follow-up visits through week 16. Patients, all on a stable dose of methotrexate, were randomized to one of three dosing regimens of Rabeximod (6.25 mg, 15 mg, or 37.5 mg once daily) or placebo. Principal Investigator was Professor Lars Klareskog, Head of Rheumatology Unit at Karolinska University Hospital, Stockholm, Sweden.
Rabeximod showed a delayed onset of action, which resulted in a significant therapeutic effect of the dosing regimen seen at 16 weeks rather than at the 12 week endpoint. At 16 weeks, the 15 mg Rabeximod dose group exhibited statistically significant (p<0.05) effects for seven of the key secondary endpoints of treatment: ACR20, DAS28 response rate, pain, subject global assessment, physician global assessment, number of swollen joints and number of tender joints. At 12 weeks, none of the treatment groups demonstrated a significant effect on the ACR20 response rate, which was the primary endpoint of the study.
The study also demonstrated a good safety profile of Rabeximod. The incidence of adverse events in the Rabeximod 6.25 mg, 15 mg and placebo groups were similar. Skin disorders were the most frequently reported adverse event, with the highest incidence in the 37.5 mg Rabeximod group, all rated mild to moderate in severity. No adverse synergistic effect was seen with methotrexate.
Based on the efficacy and safety results, 15 mg Rabeximod administered once daily appears to be the most optimal dose. These results indicate that the treatment duration of 12 weeks in the study was too short to reach an optimal clinical effect of Rabeximod in combination with methotrexate. The full potential of Rabeximod in the treatment of patients with rheumatoid arthritis will be revealed in studies designed with a longer duration of treatment.
“This is the first clinical trial evaluating the effect of Rabeximod for the treatment of moderate or severe rheumatoid arthritis”, said Ulf Björklund, CEO, OxyPharma. “The study suggests that Rabeximod causes a beneficial modification of disease activity with a delayed onset of its therapeutic benefits. The results thus indicate that a three month treatment period was not sufficient to observe the full therapeutic effect of the drug. This outcome is what can be expected with a disease-modifying anti-rheumatic drug where the effect appears slowly and lasts longer, especially since the compound has a long half-life. As the main variables are statistically significant at week 16, OxyPharma is confident that studies with longer treatment duration will prove oral Rabeximod to be an effective, convenient and safe drug for commercialization”.
Partnering Strategy “The management and the board of OxyPharma consider the results very encouraging for further development of Rabeximod. We have therefore decided to invite pharmaceutical companies for partnering discussions. OxyPharma is in the process of appointing an advisor to assist in this process”, said Mr. Björklund.
Rheumatoid Arthritis Market Estimates of the value of the global rheumatoid arthritis market vary between USD 6 and 13 billion annually. The market growth is significant. There are presently no effective, safe and oral drugs for rheumatoid arthritis treatments.
About Rabeximod: Rabeximod is an orally available small molecule that is first-in-class and classified as a disease-modifying anti-rheumatic drug. Its mechanism of action is an interaction with the inflammatory tissue type A cells, often described as macrophages. In vitro data on human peripheral blood cells show that Rabeximod suppresses the differentiation of monocytes into pro-inflammatory macrophages but not anti-inflammatory macrophages. The inflammatory macrophage is the central orchestrator of the inflammatory response leading to tissue destruction and clinical symptoms. Thus, the macrophages is a key cell in immune presentation of antigens and plays a role in both the initiating phase of the inflammation as well as in perpetuating the inflammatory process.
The commercial use of Rabeximod and related compounds as a rheumatoid arthritis medication is covered by strong patents.
The study was designed to reveal an effect of Rabeximod at 12 weeks (primary endpoint), based on the assumption of a similar onset of action as other disease-modifying anti-rheumatic drugs. Treatment with Rabeximod was given during 12 weeks to 224 patients with moderate or severe active rheumatoid arthritis that were not fully responsive to prior treatment withmethotrexate , with clinical follow-up visits through week 16. Patients, all on a stable dose of methotrexate, were randomized to one of three dosing regimens of Rabeximod (6.25 mg, 15 mg, or 37.5 mg once daily) or placebo. Principal Investigator was Professor Lars Klareskog, Head of Rheumatology Unit at Karolinska University Hospital, Stockholm, Sweden.
Rabeximod showed a delayed onset of action, which resulted in a significant therapeutic effect of the dosing regimen seen at 16 weeks rather than at the 12 week endpoint. At 16 weeks, the 15 mg Rabeximod dose group exhibited statistically significant (p<0.05) effects for seven of the key secondary endpoints of treatment: ACR20, DAS28 response rate, pain, subject global assessment, physician global assessment, number of swollen joints and number of tender joints. At 12 weeks, none of the treatment groups demonstrated a significant effect on the ACR20 response rate, which was the primary endpoint of the study.
The study also demonstrated a good safety profile of Rabeximod. The incidence of adverse events in the Rabeximod 6.25 mg, 15 mg and placebo groups were similar. Skin disorders were the most frequently reported adverse event, with the highest incidence in the 37.5 mg Rabeximod group, all rated mild to moderate in severity. No adverse synergistic effect was seen with methotrexate.
Based on the efficacy and safety results, 15 mg Rabeximod administered once daily appears to be the most optimal dose. These results indicate that the treatment duration of 12 weeks in the study was too short to reach an optimal clinical effect of Rabeximod in combination with methotrexate. The full potential of Rabeximod in the treatment of patients with rheumatoid arthritis will be revealed in studies designed with a longer duration of treatment.
“This is the first clinical trial evaluating the effect of Rabeximod for the treatment of moderate or severe rheumatoid arthritis”, said Ulf Björklund, CEO, OxyPharma. “The study suggests that Rabeximod causes a beneficial modification of disease activity with a delayed onset of its therapeutic benefits. The results thus indicate that a three month treatment period was not sufficient to observe the full therapeutic effect of the drug. This outcome is what can be expected with a disease-modifying anti-rheumatic drug where the effect appears slowly and lasts longer, especially since the compound has a long half-life. As the main variables are statistically significant at week 16, OxyPharma is confident that studies with longer treatment duration will prove oral Rabeximod to be an effective, convenient and safe drug for commercialization”.
Partnering Strategy “The management and the board of OxyPharma consider the results very encouraging for further development of Rabeximod. We have therefore decided to invite pharmaceutical companies for partnering discussions. OxyPharma is in the process of appointing an advisor to assist in this process”, said Mr. Björklund.
Rheumatoid Arthritis Market Estimates of the value of the global rheumatoid arthritis market vary between USD 6 and 13 billion annually. The market growth is significant. There are presently no effective, safe and oral drugs for rheumatoid arthritis treatments.
About Rabeximod: Rabeximod is an orally available small molecule that is first-in-class and classified as a disease-modifying anti-rheumatic drug. Its mechanism of action is an interaction with the inflammatory tissue type A cells, often described as macrophages. In vitro data on human peripheral blood cells show that Rabeximod suppresses the differentiation of monocytes into pro-inflammatory macrophages but not anti-inflammatory macrophages. The inflammatory macrophage is the central orchestrator of the inflammatory response leading to tissue destruction and clinical symptoms. Thus, the macrophages is a key cell in immune presentation of antigens and plays a role in both the initiating phase of the inflammation as well as in perpetuating the inflammatory process.
The commercial use of Rabeximod and related compounds as a rheumatoid arthritis medication is covered by strong patents.
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