Meeting News

Tanezumab safe, effective against OA

CHICAGO — A recent study showed that tanezumab was well-tolerated and superior to placebo in patients with osteoarthritis.

This analysis is the first completed clinical trial examining the investigational monoclonal antibody, which targets the nerve growth factor (NGF), since the FDA lifted its partial clinical hold on research of the drug.

Previous studies with tanezumab, when it was administered intravenously, demonstrated efficacy in OA and chronic low back pain,” Thomas J. Schnitzer, MD, PhD, professor of physical medicine and rehabilitation, anesthesiology and medicine at Northwestern University, Feinberg School of Medicine, said during a presentation at the ACR/ARHP 2018 Annual Meeting. “These trials, along with other trials of anti-NGF monoclonal antibodies, were put on a partial clinical hold by the FDA in 2010 because of concerns about joint safety. The trials were later put on another clinical hold because of some preclinical concerns about sympathetic safety.”

Upon further review, the FDA decided to lift its partial clinical hold, and co-manufacturers Pfizer Inc. and Eli Lilly and Company relaunched their phase 3 clinical program of tanezumab in March 2015. Last year, the FDA granted tanezumab fast track designation.

For the current study, Schnitzer and colleagues assessed the safety and efficacy of tanezumab in 696 patients with moderate-to-severe hip or knee OA who did not respond to or could not tolerate standard pain treatment. The participants were randomly assigned to receive one of three treatment groups: 2.5 mg of subcutaneous tanezumab at baseline and week 8 (standard tanezumab group; n = 231); 2.5 mg of subcutaneous tanezumab at baseline and 5 mg at week 8 (titrated tanezumab group; n = 233); or placebo (n = 232).

The primary endpoints included changes in pain, physical function and patient global assessments (PGA) of OA from baseline to week 16. A follow-up safety analysis was conducted for an additional 24 weeks. All joint safety events were reviewed by a blinded adjudication committee. Neurological exams were conducted at each patient visit, and specialists were consulted based on protocol-specified parameters.

At week 16, tanezumab significantly improved WOMAC pain scores, WOMAC physical function scores and PGA of OA. These improvements were slightly greater among patients who received the 5-mg dose at week 8.

Overall, there was a 30% or more reduction in WOMAC pain scores among 70.4% of patients in the titrated tanezumab group, 68% of patients in the standard tanezumab group, and 54.7% of patients in the placebo group. Meanwhile, there was a 50% or more reduction in pain scores among 57.1% of patients in the titrated tanezumab group, 54.5% in the standard tanezumab group, and 37.9% in the placebo group.

Approximately half of patients in each group had at least one adverse event. Treatment-related adverse events occurred among 10.3% of patients who received placebo, 12.6% who received standard tanezumab and 9.4% who received titrated tanezumab. Less than 1% of patients in each group withdrew from the study due to adverse events, none of which were related to tanezumab.

Sixteen patients in the titrated tanezumab group, eight patients in the standard tanezumab group and four patients in the placebo group underwent a total joint replacement (TJR). Most TJR events (93%) were adjudicated as normal OA progression, and 75% were considered elective surgeries. Nearly 70% of TJR events occurred after the end of the treatment period.

The overall incidence of adjudicated rapidly progressive OA was 1.3% among patients who received tanezumab, 0.4% of which resulted in TJR. There were 14 joint safety events among patients in the standard tanezumab group, 18 events in the titrated tanezumab group and five events in the placebo group. Most joint safety events were attributed to normal progression of OA, Schnitzer reported.

“There obviously is an imbalance in the incidence of TJR in the active treatment group vs. placebo group,” Schnitzer said. “The reason for this is unknown, but this is not consistent with prior data. Earlier studies with tanezumab showed that the rate of TJR was similar in the placebo groups, active treatment groups, and groups treated with nonsteroidals. This was true even with higher doses of tanezumab.”

In a neurological safety analysis, Schnitzer said there was no indication of any sympathetic nervous system events.

“In conclusion, tanezumab at both 2.5 mg and 2.5 mg titrated to 5 mg demonstrated superior efficacy compared to placebo in patients with OA,” he said. “Tanezumab was generally safe and well-tolerated at both doses. Two larger, longer-duration trials with tanezumab that are ongoing will provide more data to better characterize the safety profile of tanezumab.” – by Stephanie Viguers

References:

Schnitzer TJ, et al. Abstract L20. Presented at: ACR/ARHP Annual Meeting, Oct. 20-24, 2018; Chicago.

Pfizer. Pfizer and Lilly Preparing to Resume Phase 3 Chronic Pain Program for Tanezumab. https://www.pfizer.com/news/press-release/press-release-detail/pfizer_and_lilly_preparing_to_resume_phase_3_chronic_pain_program_for_tanezumab. Accessed Nov. 20, 2018.

Disclosure: Schnitzer reports performing clinical research for AbbVie, Eli Lilly & Company, Grunenthal, Pfizer and Radius and receiving consulting fees from AbbVie, Aptinyx, Eli Lilly & Company, Genzyme, Pfizer, Regeneron, and Vertex.

CHICAGO — A recent study showed that tanezumab was well-tolerated and superior to placebo in patients with osteoarthritis.

This analysis is the first completed clinical trial examining the investigational monoclonal antibody, which targets the nerve growth factor (NGF), since the FDA lifted its partial clinical hold on research of the drug.

Previous studies with tanezumab, when it was administered intravenously, demonstrated efficacy in OA and chronic low back pain,” Thomas J. Schnitzer, MD, PhD, professor of physical medicine and rehabilitation, anesthesiology and medicine at Northwestern University, Feinberg School of Medicine, said during a presentation at the ACR/ARHP 2018 Annual Meeting. “These trials, along with other trials of anti-NGF monoclonal antibodies, were put on a partial clinical hold by the FDA in 2010 because of concerns about joint safety. The trials were later put on another clinical hold because of some preclinical concerns about sympathetic safety.”

Upon further review, the FDA decided to lift its partial clinical hold, and co-manufacturers Pfizer Inc. and Eli Lilly and Company relaunched their phase 3 clinical program of tanezumab in March 2015. Last year, the FDA granted tanezumab fast track designation.

For the current study, Schnitzer and colleagues assessed the safety and efficacy of tanezumab in 696 patients with moderate-to-severe hip or knee OA who did not respond to or could not tolerate standard pain treatment. The participants were randomly assigned to receive one of three treatment groups: 2.5 mg of subcutaneous tanezumab at baseline and week 8 (standard tanezumab group; n = 231); 2.5 mg of subcutaneous tanezumab at baseline and 5 mg at week 8 (titrated tanezumab group; n = 233); or placebo (n = 232).

The primary endpoints included changes in pain, physical function and patient global assessments (PGA) of OA from baseline to week 16. A follow-up safety analysis was conducted for an additional 24 weeks. All joint safety events were reviewed by a blinded adjudication committee. Neurological exams were conducted at each patient visit, and specialists were consulted based on protocol-specified parameters.

At week 16, tanezumab significantly improved WOMAC pain scores, WOMAC physical function scores and PGA of OA. These improvements were slightly greater among patients who received the 5-mg dose at week 8.

Overall, there was a 30% or more reduction in WOMAC pain scores among 70.4% of patients in the titrated tanezumab group, 68% of patients in the standard tanezumab group, and 54.7% of patients in the placebo group. Meanwhile, there was a 50% or more reduction in pain scores among 57.1% of patients in the titrated tanezumab group, 54.5% in the standard tanezumab group, and 37.9% in the placebo group.

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Approximately half of patients in each group had at least one adverse event. Treatment-related adverse events occurred among 10.3% of patients who received placebo, 12.6% who received standard tanezumab and 9.4% who received titrated tanezumab. Less than 1% of patients in each group withdrew from the study due to adverse events, none of which were related to tanezumab.

Sixteen patients in the titrated tanezumab group, eight patients in the standard tanezumab group and four patients in the placebo group underwent a total joint replacement (TJR). Most TJR events (93%) were adjudicated as normal OA progression, and 75% were considered elective surgeries. Nearly 70% of TJR events occurred after the end of the treatment period.

The overall incidence of adjudicated rapidly progressive OA was 1.3% among patients who received tanezumab, 0.4% of which resulted in TJR. There were 14 joint safety events among patients in the standard tanezumab group, 18 events in the titrated tanezumab group and five events in the placebo group. Most joint safety events were attributed to normal progression of OA, Schnitzer reported.

“There obviously is an imbalance in the incidence of TJR in the active treatment group vs. placebo group,” Schnitzer said. “The reason for this is unknown, but this is not consistent with prior data. Earlier studies with tanezumab showed that the rate of TJR was similar in the placebo groups, active treatment groups, and groups treated with nonsteroidals. This was true even with higher doses of tanezumab.”

In a neurological safety analysis, Schnitzer said there was no indication of any sympathetic nervous system events.

“In conclusion, tanezumab at both 2.5 mg and 2.5 mg titrated to 5 mg demonstrated superior efficacy compared to placebo in patients with OA,” he said. “Tanezumab was generally safe and well-tolerated at both doses. Two larger, longer-duration trials with tanezumab that are ongoing will provide more data to better characterize the safety profile of tanezumab.” – by Stephanie Viguers

References:

Schnitzer TJ, et al. Abstract L20. Presented at: ACR/ARHP Annual Meeting, Oct. 20-24, 2018; Chicago.

Pfizer. Pfizer and Lilly Preparing to Resume Phase 3 Chronic Pain Program for Tanezumab. https://www.pfizer.com/news/press-release/press-release-detail/pfizer_and_lilly_preparing_to_resume_phase_3_chronic_pain_program_for_tanezumab. Accessed Nov. 20, 2018.

Disclosure: Schnitzer reports performing clinical research for AbbVie, Eli Lilly & Company, Grunenthal, Pfizer and Radius and receiving consulting fees from AbbVie, Aptinyx, Eli Lilly & Company, Genzyme, Pfizer, Regeneron, and Vertex.

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