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Ubrogepant, an oral calcitonin gene–related peptide (CGRP)–receptor antagonist, may relieve patients’ migraine pain and their most bothersome associated symptom, such as photophobia, phonophobia, or nausea, at 2 hours after acute treatment, according to phase 3 trial results published Nov. 19 in JAMA.
“Among adults with migraine, acute treatment with ubrogepant, compared with placebo, led to significantly greater rates of pain freedom at 2 hours with the 50-mg and 25-mg doses, and absence of the most bothersome migraine-associated symptom at 2 hours only with the 50-mg dose,” wrote first author Richard B. Lipton, MD, director of the Montefiore Headache Center at Albert Einstein College of Medicine, New York, and his colleagues. “Further research is needed to assess the effectiveness of ubrogepant against other acute treatments for migraine and to evaluate the long-term safety of ubrogepant among unselected patient populations.”
A researcher who commented on the results said that the drug appears “modestly better than placebo” and called for a trial comparing ubrogepant, aspirin, and oral sumatriptan.
The Food and Drug Administration is reviewing an application for ubrogepant. Allergan, the company developing the drug, has said it expects a regulatory decision in December.
ACHIEVE II
To evaluate the efficacy and tolerability of ubrogepant versus placebo for the acute treatment of a migraine attack, investigators conducted ACHIEVE II, a randomized, double-blind, placebo-controlled, single-attack clinical trial. The study was conducted at 99 primary care and research clinics during 2016-2018.
The trial included adults with migraine with or without aura who experienced two to eight migraine attacks per month. Participants had a mean age of 41.5 years, and 90% were female. The safety analysis included data from 1,465 participants, and the efficacy analysis included data from 1,355 participants. The primary efficacy outcomes were pain freedom and the absence of participants’ most bothersome migraine-associated symptom at 2 hours after taking the medication. Patients received ubrogepant 50 mg, ubrogepant 25 mg, or placebo to treat a migraine attack of moderate or severe pain intensity.
At 2 hours, pain freedom was reported by 101 of 464 participants in the ubrogepant 50-mg group (21.8%), 90 of 435 in the ubrogepant 25-mg group (20.7%), and 65 of 456 in the placebo group (14.3%). Absence of the most bothersome symptom was reported by 180 of 463 participants in the ubrogepant 50-mg group (38.9%), 148 of 434 in the ubrogepant 25-mg group (34.1%), and 125 of 456 in the placebo group (27.4%).
The most common adverse events within 48 hours were nausea and dizziness. Nausea occurred in 2.0% of the 50-mg group, 2.5% of the 25-mg group, and 2.0% of the placebo group. Dizziness occurred in 1.4% of the 50-mg group, 2.1% of the 25-mg group, and 1.6% of the placebo group.
At conferences, researchers have presented results from the phase 3 ACHIEVE I trial as well as an analysis that suggests ubrogepant may be effective in patients for whom triptans have been ineffective. In addition, studies have supported the safety of “gepants” after earlier concerns about potential liver toxicity. Physicians have called the safety data reassuring.
The ACHIEVE II trial was sponsored by Allergan. Several authors are Allergan employees. Dr. Lipton is a consultant, advisory board member, or has received honoraria from Allergan and other companies.
Number needed to treat
“The study was large, appears to have been well conducted, is clearly reported, and used appropriate outcome measures,” said Elizabeth Loder, MD, commenting on the trial.
A year ago, Dr. Loder, chief of the division of headache at Brigham and Women’s Hospital and professor of neurology at Harvard Medical School in Boston, coauthored a paper with Peer Tfelt-Hansen, MD, DMSc, of the University of Copenhagen, that said the phase 3 trials of gepants so far have found the drugs to have small effect sizes and low efficacy (Headache. 2019 Jan;59[1]:113-7. doi: 10.1111/head.13444).
Their publication included preliminary figures from ACHIEVE II, which are consistent with those published in JAMA. “The effect size for both doses of ubrogepant is small and of debatable clinical significance,” Dr. Loder said. “The therapeutic gain over placebo is 7.5% for the 50-mg dose and 6.4% for the 25-mg dose for the outcome of pain freedom at 2 hours. That corresponds to a number needed to treat of 13 and 15.6 people, respectively, in order to have one person achieve pain freedom at 2 hours that is attributable to the active treatment.”
For a secondary outcome of pain relief at 2 hours, defined as reduction of headache pain severity from moderate or severe to mild or none, the therapeutic gain versus placebo is 14.5% for the 50-mg dose and 12.3% for the 25-mg dose. “That corresponds to a number needed to treat of 6.8 and 8.1 people, respectively, to have one person achieve pain relief at 2 hours attributable to the drug,” Dr. Loder said.
“Although there are no head to head studies comparing ubrogepant to triptans, for reference the [number needed to treat] for a 100-mg oral dose of sumatriptan is on the order of 3.5 for pain relief at 2 hours, meaning that one needs to treat just 3.5 people with sumatriptan in order to have one person achieve pain relief at 2 hours attributable to the drug,” she said (Cochrane Database Syst Rev. 2014;5:CD009108. doi: 10.1002/14651858.CD009108.pub2).
“The bottom line is that in the ACHIEVE II study, ubrogepant appears, on average, to be modestly better than placebo to treat migraine. It does not appear to be in the same league as sumatriptan. Instead, as Dr. Tfelt-Hansen and I said in our article, the results look comparable to those likely to be achieved with inexpensive nonprescription medications such as NSAIDs.”
Dr. Loder called for a trial comparing ubrogepant and other therapies. “I challenge the authors and the company to conduct a large, placebo-controlled trial comparing ubrogepant to 100 mg of oral sumatriptan and to 650 mg of aspirin,” Dr. Loder said.
Dr. Loder has no financial connections with any pharmaceutical or device companies and is paid for her work as the head of research for the British Medical Journal.
SOURCE: Lipton RB et al. JAMA. 2019;322(19):1887-98. doi: 10.1001/jama.2019.16711.
Ubrogepant, an oral calcitonin gene–related peptide (CGRP)–receptor antagonist, may relieve patients’ migraine pain and their most bothersome associated symptom, such as photophobia, phonophobia, or nausea, at 2 hours after acute treatment, according to phase 3 trial results published Nov. 19 in JAMA.
“Among adults with migraine, acute treatment with ubrogepant, compared with placebo, led to significantly greater rates of pain freedom at 2 hours with the 50-mg and 25-mg doses, and absence of the most bothersome migraine-associated symptom at 2 hours only with the 50-mg dose,” wrote first author Richard B. Lipton, MD, director of the Montefiore Headache Center at Albert Einstein College of Medicine, New York, and his colleagues. “Further research is needed to assess the effectiveness of ubrogepant against other acute treatments for migraine and to evaluate the long-term safety of ubrogepant among unselected patient populations.”
A researcher who commented on the results said that the drug appears “modestly better than placebo” and called for a trial comparing ubrogepant, aspirin, and oral sumatriptan.
The Food and Drug Administration is reviewing an application for ubrogepant. Allergan, the company developing the drug, has said it expects a regulatory decision in December.
ACHIEVE II
To evaluate the efficacy and tolerability of ubrogepant versus placebo for the acute treatment of a migraine attack, investigators conducted ACHIEVE II, a randomized, double-blind, placebo-controlled, single-attack clinical trial. The study was conducted at 99 primary care and research clinics during 2016-2018.
The trial included adults with migraine with or without aura who experienced two to eight migraine attacks per month. Participants had a mean age of 41.5 years, and 90% were female. The safety analysis included data from 1,465 participants, and the efficacy analysis included data from 1,355 participants. The primary efficacy outcomes were pain freedom and the absence of participants’ most bothersome migraine-associated symptom at 2 hours after taking the medication. Patients received ubrogepant 50 mg, ubrogepant 25 mg, or placebo to treat a migraine attack of moderate or severe pain intensity.
At 2 hours, pain freedom was reported by 101 of 464 participants in the ubrogepant 50-mg group (21.8%), 90 of 435 in the ubrogepant 25-mg group (20.7%), and 65 of 456 in the placebo group (14.3%). Absence of the most bothersome symptom was reported by 180 of 463 participants in the ubrogepant 50-mg group (38.9%), 148 of 434 in the ubrogepant 25-mg group (34.1%), and 125 of 456 in the placebo group (27.4%).
The most common adverse events within 48 hours were nausea and dizziness. Nausea occurred in 2.0% of the 50-mg group, 2.5% of the 25-mg group, and 2.0% of the placebo group. Dizziness occurred in 1.4% of the 50-mg group, 2.1% of the 25-mg group, and 1.6% of the placebo group.
At conferences, researchers have presented results from the phase 3 ACHIEVE I trial as well as an analysis that suggests ubrogepant may be effective in patients for whom triptans have been ineffective. In addition, studies have supported the safety of “gepants” after earlier concerns about potential liver toxicity. Physicians have called the safety data reassuring.
The ACHIEVE II trial was sponsored by Allergan. Several authors are Allergan employees. Dr. Lipton is a consultant, advisory board member, or has received honoraria from Allergan and other companies.
Number needed to treat
“The study was large, appears to have been well conducted, is clearly reported, and used appropriate outcome measures,” said Elizabeth Loder, MD, commenting on the trial.
A year ago, Dr. Loder, chief of the division of headache at Brigham and Women’s Hospital and professor of neurology at Harvard Medical School in Boston, coauthored a paper with Peer Tfelt-Hansen, MD, DMSc, of the University of Copenhagen, that said the phase 3 trials of gepants so far have found the drugs to have small effect sizes and low efficacy (Headache. 2019 Jan;59[1]:113-7. doi: 10.1111/head.13444).
Their publication included preliminary figures from ACHIEVE II, which are consistent with those published in JAMA. “The effect size for both doses of ubrogepant is small and of debatable clinical significance,” Dr. Loder said. “The therapeutic gain over placebo is 7.5% for the 50-mg dose and 6.4% for the 25-mg dose for the outcome of pain freedom at 2 hours. That corresponds to a number needed to treat of 13 and 15.6 people, respectively, in order to have one person achieve pain freedom at 2 hours that is attributable to the active treatment.”
For a secondary outcome of pain relief at 2 hours, defined as reduction of headache pain severity from moderate or severe to mild or none, the therapeutic gain versus placebo is 14.5% for the 50-mg dose and 12.3% for the 25-mg dose. “That corresponds to a number needed to treat of 6.8 and 8.1 people, respectively, to have one person achieve pain relief at 2 hours attributable to the drug,” Dr. Loder said.
“Although there are no head to head studies comparing ubrogepant to triptans, for reference the [number needed to treat] for a 100-mg oral dose of sumatriptan is on the order of 3.5 for pain relief at 2 hours, meaning that one needs to treat just 3.5 people with sumatriptan in order to have one person achieve pain relief at 2 hours attributable to the drug,” she said (Cochrane Database Syst Rev. 2014;5:CD009108. doi: 10.1002/14651858.CD009108.pub2).
“The bottom line is that in the ACHIEVE II study, ubrogepant appears, on average, to be modestly better than placebo to treat migraine. It does not appear to be in the same league as sumatriptan. Instead, as Dr. Tfelt-Hansen and I said in our article, the results look comparable to those likely to be achieved with inexpensive nonprescription medications such as NSAIDs.”
Dr. Loder called for a trial comparing ubrogepant and other therapies. “I challenge the authors and the company to conduct a large, placebo-controlled trial comparing ubrogepant to 100 mg of oral sumatriptan and to 650 mg of aspirin,” Dr. Loder said.
Dr. Loder has no financial connections with any pharmaceutical or device companies and is paid for her work as the head of research for the British Medical Journal.
SOURCE: Lipton RB et al. JAMA. 2019;322(19):1887-98. doi: 10.1001/jama.2019.16711.
Ubrogepant, an oral calcitonin gene–related peptide (CGRP)–receptor antagonist, may relieve patients’ migraine pain and their most bothersome associated symptom, such as photophobia, phonophobia, or nausea, at 2 hours after acute treatment, according to phase 3 trial results published Nov. 19 in JAMA.
“Among adults with migraine, acute treatment with ubrogepant, compared with placebo, led to significantly greater rates of pain freedom at 2 hours with the 50-mg and 25-mg doses, and absence of the most bothersome migraine-associated symptom at 2 hours only with the 50-mg dose,” wrote first author Richard B. Lipton, MD, director of the Montefiore Headache Center at Albert Einstein College of Medicine, New York, and his colleagues. “Further research is needed to assess the effectiveness of ubrogepant against other acute treatments for migraine and to evaluate the long-term safety of ubrogepant among unselected patient populations.”
A researcher who commented on the results said that the drug appears “modestly better than placebo” and called for a trial comparing ubrogepant, aspirin, and oral sumatriptan.
The Food and Drug Administration is reviewing an application for ubrogepant. Allergan, the company developing the drug, has said it expects a regulatory decision in December.
ACHIEVE II
To evaluate the efficacy and tolerability of ubrogepant versus placebo for the acute treatment of a migraine attack, investigators conducted ACHIEVE II, a randomized, double-blind, placebo-controlled, single-attack clinical trial. The study was conducted at 99 primary care and research clinics during 2016-2018.
The trial included adults with migraine with or without aura who experienced two to eight migraine attacks per month. Participants had a mean age of 41.5 years, and 90% were female. The safety analysis included data from 1,465 participants, and the efficacy analysis included data from 1,355 participants. The primary efficacy outcomes were pain freedom and the absence of participants’ most bothersome migraine-associated symptom at 2 hours after taking the medication. Patients received ubrogepant 50 mg, ubrogepant 25 mg, or placebo to treat a migraine attack of moderate or severe pain intensity.
At 2 hours, pain freedom was reported by 101 of 464 participants in the ubrogepant 50-mg group (21.8%), 90 of 435 in the ubrogepant 25-mg group (20.7%), and 65 of 456 in the placebo group (14.3%). Absence of the most bothersome symptom was reported by 180 of 463 participants in the ubrogepant 50-mg group (38.9%), 148 of 434 in the ubrogepant 25-mg group (34.1%), and 125 of 456 in the placebo group (27.4%).
The most common adverse events within 48 hours were nausea and dizziness. Nausea occurred in 2.0% of the 50-mg group, 2.5% of the 25-mg group, and 2.0% of the placebo group. Dizziness occurred in 1.4% of the 50-mg group, 2.1% of the 25-mg group, and 1.6% of the placebo group.
At conferences, researchers have presented results from the phase 3 ACHIEVE I trial as well as an analysis that suggests ubrogepant may be effective in patients for whom triptans have been ineffective. In addition, studies have supported the safety of “gepants” after earlier concerns about potential liver toxicity. Physicians have called the safety data reassuring.
The ACHIEVE II trial was sponsored by Allergan. Several authors are Allergan employees. Dr. Lipton is a consultant, advisory board member, or has received honoraria from Allergan and other companies.
Number needed to treat
“The study was large, appears to have been well conducted, is clearly reported, and used appropriate outcome measures,” said Elizabeth Loder, MD, commenting on the trial.
A year ago, Dr. Loder, chief of the division of headache at Brigham and Women’s Hospital and professor of neurology at Harvard Medical School in Boston, coauthored a paper with Peer Tfelt-Hansen, MD, DMSc, of the University of Copenhagen, that said the phase 3 trials of gepants so far have found the drugs to have small effect sizes and low efficacy (Headache. 2019 Jan;59[1]:113-7. doi: 10.1111/head.13444).
Their publication included preliminary figures from ACHIEVE II, which are consistent with those published in JAMA. “The effect size for both doses of ubrogepant is small and of debatable clinical significance,” Dr. Loder said. “The therapeutic gain over placebo is 7.5% for the 50-mg dose and 6.4% for the 25-mg dose for the outcome of pain freedom at 2 hours. That corresponds to a number needed to treat of 13 and 15.6 people, respectively, in order to have one person achieve pain freedom at 2 hours that is attributable to the active treatment.”
For a secondary outcome of pain relief at 2 hours, defined as reduction of headache pain severity from moderate or severe to mild or none, the therapeutic gain versus placebo is 14.5% for the 50-mg dose and 12.3% for the 25-mg dose. “That corresponds to a number needed to treat of 6.8 and 8.1 people, respectively, to have one person achieve pain relief at 2 hours attributable to the drug,” Dr. Loder said.
“Although there are no head to head studies comparing ubrogepant to triptans, for reference the [number needed to treat] for a 100-mg oral dose of sumatriptan is on the order of 3.5 for pain relief at 2 hours, meaning that one needs to treat just 3.5 people with sumatriptan in order to have one person achieve pain relief at 2 hours attributable to the drug,” she said (Cochrane Database Syst Rev. 2014;5:CD009108. doi: 10.1002/14651858.CD009108.pub2).
“The bottom line is that in the ACHIEVE II study, ubrogepant appears, on average, to be modestly better than placebo to treat migraine. It does not appear to be in the same league as sumatriptan. Instead, as Dr. Tfelt-Hansen and I said in our article, the results look comparable to those likely to be achieved with inexpensive nonprescription medications such as NSAIDs.”
Dr. Loder called for a trial comparing ubrogepant and other therapies. “I challenge the authors and the company to conduct a large, placebo-controlled trial comparing ubrogepant to 100 mg of oral sumatriptan and to 650 mg of aspirin,” Dr. Loder said.
Dr. Loder has no financial connections with any pharmaceutical or device companies and is paid for her work as the head of research for the British Medical Journal.
SOURCE: Lipton RB et al. JAMA. 2019;322(19):1887-98. doi: 10.1001/jama.2019.16711.
FROM JAMA