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, data from a new phase 3 study showed.
After 6 weeks of treatment, patients reported nearly 60% sustained improvement in daily activities and a rapid onset of action from batoclimab, a neonatal crystallizable fragment receptor (FcRn) antagonist.
The clinical effects and the extent of immunoglobulin G (IgG) reduction in this study were similar to those previously reported for efgartigimod and rozanolixizumab, two other FcRn antagonists, the investigators noted, adding that larger studies are needed to better understand the safety profile of batoclimab.
“While most generalized myasthenia gravis patients can achieve good disease control through conventional immunotherapy, there are still unmet needs with this disease,” said study investigator Chongbo Zhao, MD, National Center for Neurological Disorders, Huashan Rare Disease Centre, Department of Neurology, Huashan Hospital of Fudan University, Shanghai, China.
The findings were published online in JAMA Neurology.
Unmet Need
A rare chronic disease, myasthenia gravis is caused by autoantibodies that disrupt the neuromuscular junction, most commonly against the nicotinic acetylcholine receptor (AChR). This can cause a variety of symptoms, including difficulty swallowing, chewing, and talking, as well as severe, sometimes life-threatening, muscle weakness.
The estimated global prevalence of myasthenia gravis is 15-25 per 100,000, with cases doubling in the past 20 years.
Treatment for myasthenia gravis typically includes immune-suppressing drugs. But research suggests almost half of patients with generalized myasthenia gravis don’t achieve an adequate response or are intolerant to these treatments, and some therapies are costly or not readily accessible.
“Our treatment goal has evolved from saving patients to improving their quality of life, so we still need to explore safer and more effective novel treatment methods,” Dr. Zhao said.
Batoclimab is a fully humanized monoclonal IgG antibody that binds to FcRn and accelerates clearance of harmful IgG. A phase 2 trial provided preliminary evidence to support the efficacy of this agent in Chinese patients with generalized myasthenia gravis.
The current double-blind phase 3 trial included 132 adult patients (mean age, 44 years; 67% female) of Chinese Han ethnicity with generalized myasthenia gravis at 27 centers in China. Participants had a mean Myasthenia Gravis Activities of Daily Living (MG-ADL) score of 8.4 at baseline, and all but one was positive for AChR or muscle-specific kinase (MuSK) antibodies.
The treatment group received weekly subcutaneous injections of batoclimab at 680 mg for 6 weeks, followed by 4 weeks of observation. The control group received a placebo with the same treatment and follow-up schedule.
All patients received standard of care in addition to the assigned treatment, but changes in dosage and/or dosing frequency were not permitted. Patients received a second cycle if they still required treatment.
Bests Placebo
Overall, 90% of participants completed all six doses in cycle 1. The second treatment cycle was conducted in 115 patients, with 88% completing all six doses.
Patients were evaluated at baseline and then weekly for MG-ADL, Quantitative Myasthenia Gravis (QMG), Myasthenia Gravis Composite, and the 15-item revised version of the Myasthenia Gravis Quality of Life.
Sustained MG-ADL improvement — the primary outcome — was significantly higher in the batoclimab group compared with placebo (58% vs 31%, respectively; odds ratio, 3.45; P = .001).
While the rate of sustained MG-ADL improvement with batoclimab was lower than that reported for efgartigimod (68%) in a previous trial, that was primarily because of the more stringent definition of sustained MG-ADL improvement (three-point reduction vs two-point reduction from baseline), investigators said.
In the current trial, batoclimab had a rapid onset of action, with scores diverging between the treatment and placebo groups as early as the second week of therapy.
In the second treatment cycle, batoclimab once again outperformed placebo in sustained MG-ADL improvement (63% vs 36%, respectively; P = .002).
Batoclimab also bested placebo on secondary outcomes, including sustained QMG improvement (64% vs 41%; P = .008) and percent of patients achieving minimal symptom expression (25% vs 5%; P = .004).
Results of all subgroup analyses, including by age groups, sex, body weight, body mass index, and MG Foundation of America clinical classification, were consistent with those of the main analysis. The efficacy of batoclimab was also supported by all sensitivity analyses, underscoring the robustness of results.
Batoclimab led to a rapid and sustained reduction in serum AChR antibody levels, with a median reduction of 81% at week 6.
Well Tolerated
On discontinuation of batoclimab, serum total IgG returned to a level comparable with the baseline after 4 weeks. Reversibility of the drug’s effect is important considering the risk for infection from prolonged immune suppression, the authors noted.
The rate of peripheral edema was significantly higher in the treatment than in the placebo groups (39% vs 5%), but all cases were mild or moderate and deemed not clinically significant. The treatment group also had higher rates of upper respiratory tract infections (36% vs 22%) and of urinary tract infections (19% vs 15%).
“Although the incidence of upper respiratory tract and urinary tract infections was higher in the batoclimab group numerically, these were mild infections that did not require special treatment, so this is not a concern,” said Dr. Zhao.
Plasma albumin levels in the batoclimab group decreased significantly throughout the treatment cycle, starting at week 1 and reaching a decline of up to 31% at week 6. These levels increased rapidly toward baseline after treatment discontinuation.
High cholesterol levels were noted in the batoclimab group, plateauing by week 6. But levels returned to near baseline levels within 4 weeks after the final dose, and there were no serious related adverse reactions.
The rate of headache was slightly higher in the treatment group (6% vs 5% for placebo). “This finding may seem minor but could potentially translate into improved adherence in daily practice settings,” the authors wrote.
In previous studies, the efficacy of FcRn inhibitors in the Asian population was only examined in subgroup analyses with limited subjects. Finding an effective FcRn antagonist for China and surrounding regions is particularly important “considering the high mortality rate in hospitalized generalized myasthenia gravis patients in China,” the researchers noted.
The trial included only two treatment cycles, although results of an open-label extension trial examining longer-term efficacy of batoclimab should be available by the end of this year, said Dr. Zhao.
The trial was also not designed to investigate long-term safety, particularly infections and cardiovascular events. Only one study subject was negative for AChR or MuSK antibodies, which prevented researchers from assessing the drug’s efficacy in this subpopulation.
Questions Remain
Commenting on the study, Fredrik Piehl, MD, PhD, professor of neurology, Karolinska Institute, Stockholm, Sweden , said that recent studies of the two other FcRn antagonists were short-term and had limited long-term data. “We don’t know how valuable they may be for continued treatment,” Dr. Piehl said.
It’s also unclear how this new treatment modality compares with existing and emerging drug strategies in terms of the long-term benefit-risk balance, he added.
The rate of adverse events with batoclimab was high compared with placebo in this study and higher than in earlier studies of efgartigimod, Dr. Piehl noted.
“In this study, almost twice as many reported adverse events in the active arm compared with controls, while these differences tended to be smaller in previously reported trials,” he said.
The trial was funded by Nona Biosciences (Suzhou). Dr. Zhao reported being a full-time employee of Nona Biosciences (Suzhou), a subsidiary of Harbour BioMed Inc. He also reported receiving advisory board/consultant fees from Nona Biosciences, Roche, Sanofi, and Zailab outside the submitted work. Dr. Piehl has received research grants from Janssen, Merck KGaA, and UCB; and fees for serving on DMC in clinical trials with Chugai, Lundbeck, and Roche; and preparation of expert witness statement for Novartis.
A version of this article first appeared on Medscape.com.
, data from a new phase 3 study showed.
After 6 weeks of treatment, patients reported nearly 60% sustained improvement in daily activities and a rapid onset of action from batoclimab, a neonatal crystallizable fragment receptor (FcRn) antagonist.
The clinical effects and the extent of immunoglobulin G (IgG) reduction in this study were similar to those previously reported for efgartigimod and rozanolixizumab, two other FcRn antagonists, the investigators noted, adding that larger studies are needed to better understand the safety profile of batoclimab.
“While most generalized myasthenia gravis patients can achieve good disease control through conventional immunotherapy, there are still unmet needs with this disease,” said study investigator Chongbo Zhao, MD, National Center for Neurological Disorders, Huashan Rare Disease Centre, Department of Neurology, Huashan Hospital of Fudan University, Shanghai, China.
The findings were published online in JAMA Neurology.
Unmet Need
A rare chronic disease, myasthenia gravis is caused by autoantibodies that disrupt the neuromuscular junction, most commonly against the nicotinic acetylcholine receptor (AChR). This can cause a variety of symptoms, including difficulty swallowing, chewing, and talking, as well as severe, sometimes life-threatening, muscle weakness.
The estimated global prevalence of myasthenia gravis is 15-25 per 100,000, with cases doubling in the past 20 years.
Treatment for myasthenia gravis typically includes immune-suppressing drugs. But research suggests almost half of patients with generalized myasthenia gravis don’t achieve an adequate response or are intolerant to these treatments, and some therapies are costly or not readily accessible.
“Our treatment goal has evolved from saving patients to improving their quality of life, so we still need to explore safer and more effective novel treatment methods,” Dr. Zhao said.
Batoclimab is a fully humanized monoclonal IgG antibody that binds to FcRn and accelerates clearance of harmful IgG. A phase 2 trial provided preliminary evidence to support the efficacy of this agent in Chinese patients with generalized myasthenia gravis.
The current double-blind phase 3 trial included 132 adult patients (mean age, 44 years; 67% female) of Chinese Han ethnicity with generalized myasthenia gravis at 27 centers in China. Participants had a mean Myasthenia Gravis Activities of Daily Living (MG-ADL) score of 8.4 at baseline, and all but one was positive for AChR or muscle-specific kinase (MuSK) antibodies.
The treatment group received weekly subcutaneous injections of batoclimab at 680 mg for 6 weeks, followed by 4 weeks of observation. The control group received a placebo with the same treatment and follow-up schedule.
All patients received standard of care in addition to the assigned treatment, but changes in dosage and/or dosing frequency were not permitted. Patients received a second cycle if they still required treatment.
Bests Placebo
Overall, 90% of participants completed all six doses in cycle 1. The second treatment cycle was conducted in 115 patients, with 88% completing all six doses.
Patients were evaluated at baseline and then weekly for MG-ADL, Quantitative Myasthenia Gravis (QMG), Myasthenia Gravis Composite, and the 15-item revised version of the Myasthenia Gravis Quality of Life.
Sustained MG-ADL improvement — the primary outcome — was significantly higher in the batoclimab group compared with placebo (58% vs 31%, respectively; odds ratio, 3.45; P = .001).
While the rate of sustained MG-ADL improvement with batoclimab was lower than that reported for efgartigimod (68%) in a previous trial, that was primarily because of the more stringent definition of sustained MG-ADL improvement (three-point reduction vs two-point reduction from baseline), investigators said.
In the current trial, batoclimab had a rapid onset of action, with scores diverging between the treatment and placebo groups as early as the second week of therapy.
In the second treatment cycle, batoclimab once again outperformed placebo in sustained MG-ADL improvement (63% vs 36%, respectively; P = .002).
Batoclimab also bested placebo on secondary outcomes, including sustained QMG improvement (64% vs 41%; P = .008) and percent of patients achieving minimal symptom expression (25% vs 5%; P = .004).
Results of all subgroup analyses, including by age groups, sex, body weight, body mass index, and MG Foundation of America clinical classification, were consistent with those of the main analysis. The efficacy of batoclimab was also supported by all sensitivity analyses, underscoring the robustness of results.
Batoclimab led to a rapid and sustained reduction in serum AChR antibody levels, with a median reduction of 81% at week 6.
Well Tolerated
On discontinuation of batoclimab, serum total IgG returned to a level comparable with the baseline after 4 weeks. Reversibility of the drug’s effect is important considering the risk for infection from prolonged immune suppression, the authors noted.
The rate of peripheral edema was significantly higher in the treatment than in the placebo groups (39% vs 5%), but all cases were mild or moderate and deemed not clinically significant. The treatment group also had higher rates of upper respiratory tract infections (36% vs 22%) and of urinary tract infections (19% vs 15%).
“Although the incidence of upper respiratory tract and urinary tract infections was higher in the batoclimab group numerically, these were mild infections that did not require special treatment, so this is not a concern,” said Dr. Zhao.
Plasma albumin levels in the batoclimab group decreased significantly throughout the treatment cycle, starting at week 1 and reaching a decline of up to 31% at week 6. These levels increased rapidly toward baseline after treatment discontinuation.
High cholesterol levels were noted in the batoclimab group, plateauing by week 6. But levels returned to near baseline levels within 4 weeks after the final dose, and there were no serious related adverse reactions.
The rate of headache was slightly higher in the treatment group (6% vs 5% for placebo). “This finding may seem minor but could potentially translate into improved adherence in daily practice settings,” the authors wrote.
In previous studies, the efficacy of FcRn inhibitors in the Asian population was only examined in subgroup analyses with limited subjects. Finding an effective FcRn antagonist for China and surrounding regions is particularly important “considering the high mortality rate in hospitalized generalized myasthenia gravis patients in China,” the researchers noted.
The trial included only two treatment cycles, although results of an open-label extension trial examining longer-term efficacy of batoclimab should be available by the end of this year, said Dr. Zhao.
The trial was also not designed to investigate long-term safety, particularly infections and cardiovascular events. Only one study subject was negative for AChR or MuSK antibodies, which prevented researchers from assessing the drug’s efficacy in this subpopulation.
Questions Remain
Commenting on the study, Fredrik Piehl, MD, PhD, professor of neurology, Karolinska Institute, Stockholm, Sweden , said that recent studies of the two other FcRn antagonists were short-term and had limited long-term data. “We don’t know how valuable they may be for continued treatment,” Dr. Piehl said.
It’s also unclear how this new treatment modality compares with existing and emerging drug strategies in terms of the long-term benefit-risk balance, he added.
The rate of adverse events with batoclimab was high compared with placebo in this study and higher than in earlier studies of efgartigimod, Dr. Piehl noted.
“In this study, almost twice as many reported adverse events in the active arm compared with controls, while these differences tended to be smaller in previously reported trials,” he said.
The trial was funded by Nona Biosciences (Suzhou). Dr. Zhao reported being a full-time employee of Nona Biosciences (Suzhou), a subsidiary of Harbour BioMed Inc. He also reported receiving advisory board/consultant fees from Nona Biosciences, Roche, Sanofi, and Zailab outside the submitted work. Dr. Piehl has received research grants from Janssen, Merck KGaA, and UCB; and fees for serving on DMC in clinical trials with Chugai, Lundbeck, and Roche; and preparation of expert witness statement for Novartis.
A version of this article first appeared on Medscape.com.
, data from a new phase 3 study showed.
After 6 weeks of treatment, patients reported nearly 60% sustained improvement in daily activities and a rapid onset of action from batoclimab, a neonatal crystallizable fragment receptor (FcRn) antagonist.
The clinical effects and the extent of immunoglobulin G (IgG) reduction in this study were similar to those previously reported for efgartigimod and rozanolixizumab, two other FcRn antagonists, the investigators noted, adding that larger studies are needed to better understand the safety profile of batoclimab.
“While most generalized myasthenia gravis patients can achieve good disease control through conventional immunotherapy, there are still unmet needs with this disease,” said study investigator Chongbo Zhao, MD, National Center for Neurological Disorders, Huashan Rare Disease Centre, Department of Neurology, Huashan Hospital of Fudan University, Shanghai, China.
The findings were published online in JAMA Neurology.
Unmet Need
A rare chronic disease, myasthenia gravis is caused by autoantibodies that disrupt the neuromuscular junction, most commonly against the nicotinic acetylcholine receptor (AChR). This can cause a variety of symptoms, including difficulty swallowing, chewing, and talking, as well as severe, sometimes life-threatening, muscle weakness.
The estimated global prevalence of myasthenia gravis is 15-25 per 100,000, with cases doubling in the past 20 years.
Treatment for myasthenia gravis typically includes immune-suppressing drugs. But research suggests almost half of patients with generalized myasthenia gravis don’t achieve an adequate response or are intolerant to these treatments, and some therapies are costly or not readily accessible.
“Our treatment goal has evolved from saving patients to improving their quality of life, so we still need to explore safer and more effective novel treatment methods,” Dr. Zhao said.
Batoclimab is a fully humanized monoclonal IgG antibody that binds to FcRn and accelerates clearance of harmful IgG. A phase 2 trial provided preliminary evidence to support the efficacy of this agent in Chinese patients with generalized myasthenia gravis.
The current double-blind phase 3 trial included 132 adult patients (mean age, 44 years; 67% female) of Chinese Han ethnicity with generalized myasthenia gravis at 27 centers in China. Participants had a mean Myasthenia Gravis Activities of Daily Living (MG-ADL) score of 8.4 at baseline, and all but one was positive for AChR or muscle-specific kinase (MuSK) antibodies.
The treatment group received weekly subcutaneous injections of batoclimab at 680 mg for 6 weeks, followed by 4 weeks of observation. The control group received a placebo with the same treatment and follow-up schedule.
All patients received standard of care in addition to the assigned treatment, but changes in dosage and/or dosing frequency were not permitted. Patients received a second cycle if they still required treatment.
Bests Placebo
Overall, 90% of participants completed all six doses in cycle 1. The second treatment cycle was conducted in 115 patients, with 88% completing all six doses.
Patients were evaluated at baseline and then weekly for MG-ADL, Quantitative Myasthenia Gravis (QMG), Myasthenia Gravis Composite, and the 15-item revised version of the Myasthenia Gravis Quality of Life.
Sustained MG-ADL improvement — the primary outcome — was significantly higher in the batoclimab group compared with placebo (58% vs 31%, respectively; odds ratio, 3.45; P = .001).
While the rate of sustained MG-ADL improvement with batoclimab was lower than that reported for efgartigimod (68%) in a previous trial, that was primarily because of the more stringent definition of sustained MG-ADL improvement (three-point reduction vs two-point reduction from baseline), investigators said.
In the current trial, batoclimab had a rapid onset of action, with scores diverging between the treatment and placebo groups as early as the second week of therapy.
In the second treatment cycle, batoclimab once again outperformed placebo in sustained MG-ADL improvement (63% vs 36%, respectively; P = .002).
Batoclimab also bested placebo on secondary outcomes, including sustained QMG improvement (64% vs 41%; P = .008) and percent of patients achieving minimal symptom expression (25% vs 5%; P = .004).
Results of all subgroup analyses, including by age groups, sex, body weight, body mass index, and MG Foundation of America clinical classification, were consistent with those of the main analysis. The efficacy of batoclimab was also supported by all sensitivity analyses, underscoring the robustness of results.
Batoclimab led to a rapid and sustained reduction in serum AChR antibody levels, with a median reduction of 81% at week 6.
Well Tolerated
On discontinuation of batoclimab, serum total IgG returned to a level comparable with the baseline after 4 weeks. Reversibility of the drug’s effect is important considering the risk for infection from prolonged immune suppression, the authors noted.
The rate of peripheral edema was significantly higher in the treatment than in the placebo groups (39% vs 5%), but all cases were mild or moderate and deemed not clinically significant. The treatment group also had higher rates of upper respiratory tract infections (36% vs 22%) and of urinary tract infections (19% vs 15%).
“Although the incidence of upper respiratory tract and urinary tract infections was higher in the batoclimab group numerically, these were mild infections that did not require special treatment, so this is not a concern,” said Dr. Zhao.
Plasma albumin levels in the batoclimab group decreased significantly throughout the treatment cycle, starting at week 1 and reaching a decline of up to 31% at week 6. These levels increased rapidly toward baseline after treatment discontinuation.
High cholesterol levels were noted in the batoclimab group, plateauing by week 6. But levels returned to near baseline levels within 4 weeks after the final dose, and there were no serious related adverse reactions.
The rate of headache was slightly higher in the treatment group (6% vs 5% for placebo). “This finding may seem minor but could potentially translate into improved adherence in daily practice settings,” the authors wrote.
In previous studies, the efficacy of FcRn inhibitors in the Asian population was only examined in subgroup analyses with limited subjects. Finding an effective FcRn antagonist for China and surrounding regions is particularly important “considering the high mortality rate in hospitalized generalized myasthenia gravis patients in China,” the researchers noted.
The trial included only two treatment cycles, although results of an open-label extension trial examining longer-term efficacy of batoclimab should be available by the end of this year, said Dr. Zhao.
The trial was also not designed to investigate long-term safety, particularly infections and cardiovascular events. Only one study subject was negative for AChR or MuSK antibodies, which prevented researchers from assessing the drug’s efficacy in this subpopulation.
Questions Remain
Commenting on the study, Fredrik Piehl, MD, PhD, professor of neurology, Karolinska Institute, Stockholm, Sweden , said that recent studies of the two other FcRn antagonists were short-term and had limited long-term data. “We don’t know how valuable they may be for continued treatment,” Dr. Piehl said.
It’s also unclear how this new treatment modality compares with existing and emerging drug strategies in terms of the long-term benefit-risk balance, he added.
The rate of adverse events with batoclimab was high compared with placebo in this study and higher than in earlier studies of efgartigimod, Dr. Piehl noted.
“In this study, almost twice as many reported adverse events in the active arm compared with controls, while these differences tended to be smaller in previously reported trials,” he said.
The trial was funded by Nona Biosciences (Suzhou). Dr. Zhao reported being a full-time employee of Nona Biosciences (Suzhou), a subsidiary of Harbour BioMed Inc. He also reported receiving advisory board/consultant fees from Nona Biosciences, Roche, Sanofi, and Zailab outside the submitted work. Dr. Piehl has received research grants from Janssen, Merck KGaA, and UCB; and fees for serving on DMC in clinical trials with Chugai, Lundbeck, and Roche; and preparation of expert witness statement for Novartis.
A version of this article first appeared on Medscape.com.
FROM JAMA NEUROLOGY