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NASHVILLE, Tennessee — , according to pharmacokinetic/pharmacodynamic (PK/PD) data from the OPERETTA 1 phase 2 clinical trial. The safety profile was similar to adult patients.
“While we believe the disease to be the same in children and adolescents, [MS] is distinguished by its very inflammatory nature, oftentimes causing two to three times the number of relapses per year as their adult-onset colleagues,” said Teri Schreiner, MD, during a presentation of the results at the annual meeting of the Consortium of Multiple Sclerosis Centers.
Approved therapies for pediatric MS include fingolimod in the United States and Europe, as well as dimethyl fumarate in Europe. “There’s a real need for high-efficacy treatment [in pediatric patients], again referring back to this disease being very inflammatory in children and adolescents. We oftentimes will use medications off label but this is clearly suboptimal as we lack safety data, and oftentimes run into difficulty with insurance approval of off-label use of medicine,” said Dr. Schreiner, who is an associate professor of neurology at University of Colorado School of Medicine, Aurora.
To determine the dose in pediatric patients that would produce comparable PK and PD to adults, the researchers dosed six patients aged 10-18 with 300 mg ocrelizumab, and 17 such patients with 600 mg ocrelizumab during a 24-week dose-exploration period, followed by a 264-week optional extension period. The cohorts were separated based on weight of less than or more than 40 kg. The mean ages were 11.2 years (mean weight, 34.9 kg) and 15.3 years (mean weight, 62.3 kg), respectively.
During the dose-exploration period, seven blood draws were performed to characterize PK. “When the PK data was analyzed, we saw that the proper cut-off point was 35 kilos. At less than 35 kilos, the appropriate dose was half of that adult dose, so 300 milligrams every 6 months, whereas above 35 kilos, the proper dose was actually 600, or the adult dose. Given the rarity of pediatric-onset MS patients less than 35 kilos, most patients will benefit from the adult dose of 600 milligrams twice yearly,” said Dr. Schreiner.
PD data were also encouraging. “The primary PD was the absence of CD-19 B cells, and that was tracked over time. While there were a few patients in both cohorts that had modest reconstitution, there was no patient in our study that crossed the retreatment threshold, and all blood samples were negative for anti-drug antibodies,” said Dr. Schreiner.
Adverse events occurred in five of six patients in the 300 mg group (83%; 4 grade 2, 1 grade 3) and 100% of patients in the 600 mg group (1 grade 1, 9 grade 2, 6 grade 3, 1 grade 4). There was one serious adverse event in the 300 mg group (16.7%) and four serious adverse events in the 600 mg group (23.5%). None led to treatment discontinuation. “This is largely consistent with what was seen in the adult studies of ocrelizumab,” said Dr. Schreiner.
Roche is now recruiting for the phase 3 OPERETTA 2 trial, which will use the 600 mg dose and compare outcomes to a fingolimod arm.
Establishing Safety in the Pediatric Population
“In [pediatric onset MS] it’s an important piece of information to design OPERETTA 2 and to dose ocrelizumab in pediatric-onset MS in general,” said Jeffrey A Cohen, MD, professor of neurology at the Cleveland Clinic, who was asked for comment.
During the Q&A period, Dr. Schreiner was asked whether it is possible to extrapolate experience from rituximab to the pediatric population. “They’re very similar molecules, and we know the mechanisms of action, but I think part of the importance of doing these studies is to get the safety data so that we actually can say with certainty, we are giving you a drug that has this list of side effects and we know about them definitively. We all use other high-efficacy medications, but I don’t think we can exactly extrapolate,” said Dr. Schreiner.
Session moderator Amy Perrin Ross, APN, noted the lack of approved pediatric therapies for MS. “This is an extremely important study, because we at least in the lower 48 are quite limited in our resources for approved pediatric cases. Information like this will make it easier for a potential pediatric indication, which would then make it easier on us to go after [treatment of the disease in this population]. The weight-based dosing, I think, is really a good thing. Patients have been asking for weight-based dosing on everything for many years,” she said.
Ahmed Obeidat, MD, PhD, associate professor at the Medical College of Wisconsin, also praised the study. “While pediatric MS is rare, it is an area of unmet need when it comes to disease-modifying therapies as only fingolimod is FDA-approved, and many use B cell–depleting therapy, such as rituximab, off label to treat children with MS with good outcomes. The need for guidance on the dosing of B cell–depleting therapy is a main priority for research in pediatric MS,” he said.
The study was funded by Roche. Dr. Schreiner has consulted for Roche and Cycle Pharmaceuticals. Dr. Cohen has consulted for Astoria, Bristol Myers Squibb, Convelo, EMD Serono Inc, FiND, INMune, and Sandoz. Dr. Obeidat has financial relationships with Alexion Pharmaceuticals, Banner Life Sciences, BD Biosciences, Biogen, Biologix Solutions, Bristol Myers Squibb, Celgene, EMD Serono, Genentech, GW Pharmaceuticals, Horizon Therapeutics, Jazz Pharmaceuticals, Novartis, Sandoz, Sanofi Genzyme, TG Therapeutics, and Viela Bio. Ms. Ross has consulted for EMD Serono, BMS, Horizon, Alexion, TG Therapeutics, Novartis, Roche, and Sanofi.
NASHVILLE, Tennessee — , according to pharmacokinetic/pharmacodynamic (PK/PD) data from the OPERETTA 1 phase 2 clinical trial. The safety profile was similar to adult patients.
“While we believe the disease to be the same in children and adolescents, [MS] is distinguished by its very inflammatory nature, oftentimes causing two to three times the number of relapses per year as their adult-onset colleagues,” said Teri Schreiner, MD, during a presentation of the results at the annual meeting of the Consortium of Multiple Sclerosis Centers.
Approved therapies for pediatric MS include fingolimod in the United States and Europe, as well as dimethyl fumarate in Europe. “There’s a real need for high-efficacy treatment [in pediatric patients], again referring back to this disease being very inflammatory in children and adolescents. We oftentimes will use medications off label but this is clearly suboptimal as we lack safety data, and oftentimes run into difficulty with insurance approval of off-label use of medicine,” said Dr. Schreiner, who is an associate professor of neurology at University of Colorado School of Medicine, Aurora.
To determine the dose in pediatric patients that would produce comparable PK and PD to adults, the researchers dosed six patients aged 10-18 with 300 mg ocrelizumab, and 17 such patients with 600 mg ocrelizumab during a 24-week dose-exploration period, followed by a 264-week optional extension period. The cohorts were separated based on weight of less than or more than 40 kg. The mean ages were 11.2 years (mean weight, 34.9 kg) and 15.3 years (mean weight, 62.3 kg), respectively.
During the dose-exploration period, seven blood draws were performed to characterize PK. “When the PK data was analyzed, we saw that the proper cut-off point was 35 kilos. At less than 35 kilos, the appropriate dose was half of that adult dose, so 300 milligrams every 6 months, whereas above 35 kilos, the proper dose was actually 600, or the adult dose. Given the rarity of pediatric-onset MS patients less than 35 kilos, most patients will benefit from the adult dose of 600 milligrams twice yearly,” said Dr. Schreiner.
PD data were also encouraging. “The primary PD was the absence of CD-19 B cells, and that was tracked over time. While there were a few patients in both cohorts that had modest reconstitution, there was no patient in our study that crossed the retreatment threshold, and all blood samples were negative for anti-drug antibodies,” said Dr. Schreiner.
Adverse events occurred in five of six patients in the 300 mg group (83%; 4 grade 2, 1 grade 3) and 100% of patients in the 600 mg group (1 grade 1, 9 grade 2, 6 grade 3, 1 grade 4). There was one serious adverse event in the 300 mg group (16.7%) and four serious adverse events in the 600 mg group (23.5%). None led to treatment discontinuation. “This is largely consistent with what was seen in the adult studies of ocrelizumab,” said Dr. Schreiner.
Roche is now recruiting for the phase 3 OPERETTA 2 trial, which will use the 600 mg dose and compare outcomes to a fingolimod arm.
Establishing Safety in the Pediatric Population
“In [pediatric onset MS] it’s an important piece of information to design OPERETTA 2 and to dose ocrelizumab in pediatric-onset MS in general,” said Jeffrey A Cohen, MD, professor of neurology at the Cleveland Clinic, who was asked for comment.
During the Q&A period, Dr. Schreiner was asked whether it is possible to extrapolate experience from rituximab to the pediatric population. “They’re very similar molecules, and we know the mechanisms of action, but I think part of the importance of doing these studies is to get the safety data so that we actually can say with certainty, we are giving you a drug that has this list of side effects and we know about them definitively. We all use other high-efficacy medications, but I don’t think we can exactly extrapolate,” said Dr. Schreiner.
Session moderator Amy Perrin Ross, APN, noted the lack of approved pediatric therapies for MS. “This is an extremely important study, because we at least in the lower 48 are quite limited in our resources for approved pediatric cases. Information like this will make it easier for a potential pediatric indication, which would then make it easier on us to go after [treatment of the disease in this population]. The weight-based dosing, I think, is really a good thing. Patients have been asking for weight-based dosing on everything for many years,” she said.
Ahmed Obeidat, MD, PhD, associate professor at the Medical College of Wisconsin, also praised the study. “While pediatric MS is rare, it is an area of unmet need when it comes to disease-modifying therapies as only fingolimod is FDA-approved, and many use B cell–depleting therapy, such as rituximab, off label to treat children with MS with good outcomes. The need for guidance on the dosing of B cell–depleting therapy is a main priority for research in pediatric MS,” he said.
The study was funded by Roche. Dr. Schreiner has consulted for Roche and Cycle Pharmaceuticals. Dr. Cohen has consulted for Astoria, Bristol Myers Squibb, Convelo, EMD Serono Inc, FiND, INMune, and Sandoz. Dr. Obeidat has financial relationships with Alexion Pharmaceuticals, Banner Life Sciences, BD Biosciences, Biogen, Biologix Solutions, Bristol Myers Squibb, Celgene, EMD Serono, Genentech, GW Pharmaceuticals, Horizon Therapeutics, Jazz Pharmaceuticals, Novartis, Sandoz, Sanofi Genzyme, TG Therapeutics, and Viela Bio. Ms. Ross has consulted for EMD Serono, BMS, Horizon, Alexion, TG Therapeutics, Novartis, Roche, and Sanofi.
NASHVILLE, Tennessee — , according to pharmacokinetic/pharmacodynamic (PK/PD) data from the OPERETTA 1 phase 2 clinical trial. The safety profile was similar to adult patients.
“While we believe the disease to be the same in children and adolescents, [MS] is distinguished by its very inflammatory nature, oftentimes causing two to three times the number of relapses per year as their adult-onset colleagues,” said Teri Schreiner, MD, during a presentation of the results at the annual meeting of the Consortium of Multiple Sclerosis Centers.
Approved therapies for pediatric MS include fingolimod in the United States and Europe, as well as dimethyl fumarate in Europe. “There’s a real need for high-efficacy treatment [in pediatric patients], again referring back to this disease being very inflammatory in children and adolescents. We oftentimes will use medications off label but this is clearly suboptimal as we lack safety data, and oftentimes run into difficulty with insurance approval of off-label use of medicine,” said Dr. Schreiner, who is an associate professor of neurology at University of Colorado School of Medicine, Aurora.
To determine the dose in pediatric patients that would produce comparable PK and PD to adults, the researchers dosed six patients aged 10-18 with 300 mg ocrelizumab, and 17 such patients with 600 mg ocrelizumab during a 24-week dose-exploration period, followed by a 264-week optional extension period. The cohorts were separated based on weight of less than or more than 40 kg. The mean ages were 11.2 years (mean weight, 34.9 kg) and 15.3 years (mean weight, 62.3 kg), respectively.
During the dose-exploration period, seven blood draws were performed to characterize PK. “When the PK data was analyzed, we saw that the proper cut-off point was 35 kilos. At less than 35 kilos, the appropriate dose was half of that adult dose, so 300 milligrams every 6 months, whereas above 35 kilos, the proper dose was actually 600, or the adult dose. Given the rarity of pediatric-onset MS patients less than 35 kilos, most patients will benefit from the adult dose of 600 milligrams twice yearly,” said Dr. Schreiner.
PD data were also encouraging. “The primary PD was the absence of CD-19 B cells, and that was tracked over time. While there were a few patients in both cohorts that had modest reconstitution, there was no patient in our study that crossed the retreatment threshold, and all blood samples were negative for anti-drug antibodies,” said Dr. Schreiner.
Adverse events occurred in five of six patients in the 300 mg group (83%; 4 grade 2, 1 grade 3) and 100% of patients in the 600 mg group (1 grade 1, 9 grade 2, 6 grade 3, 1 grade 4). There was one serious adverse event in the 300 mg group (16.7%) and four serious adverse events in the 600 mg group (23.5%). None led to treatment discontinuation. “This is largely consistent with what was seen in the adult studies of ocrelizumab,” said Dr. Schreiner.
Roche is now recruiting for the phase 3 OPERETTA 2 trial, which will use the 600 mg dose and compare outcomes to a fingolimod arm.
Establishing Safety in the Pediatric Population
“In [pediatric onset MS] it’s an important piece of information to design OPERETTA 2 and to dose ocrelizumab in pediatric-onset MS in general,” said Jeffrey A Cohen, MD, professor of neurology at the Cleveland Clinic, who was asked for comment.
During the Q&A period, Dr. Schreiner was asked whether it is possible to extrapolate experience from rituximab to the pediatric population. “They’re very similar molecules, and we know the mechanisms of action, but I think part of the importance of doing these studies is to get the safety data so that we actually can say with certainty, we are giving you a drug that has this list of side effects and we know about them definitively. We all use other high-efficacy medications, but I don’t think we can exactly extrapolate,” said Dr. Schreiner.
Session moderator Amy Perrin Ross, APN, noted the lack of approved pediatric therapies for MS. “This is an extremely important study, because we at least in the lower 48 are quite limited in our resources for approved pediatric cases. Information like this will make it easier for a potential pediatric indication, which would then make it easier on us to go after [treatment of the disease in this population]. The weight-based dosing, I think, is really a good thing. Patients have been asking for weight-based dosing on everything for many years,” she said.
Ahmed Obeidat, MD, PhD, associate professor at the Medical College of Wisconsin, also praised the study. “While pediatric MS is rare, it is an area of unmet need when it comes to disease-modifying therapies as only fingolimod is FDA-approved, and many use B cell–depleting therapy, such as rituximab, off label to treat children with MS with good outcomes. The need for guidance on the dosing of B cell–depleting therapy is a main priority for research in pediatric MS,” he said.
The study was funded by Roche. Dr. Schreiner has consulted for Roche and Cycle Pharmaceuticals. Dr. Cohen has consulted for Astoria, Bristol Myers Squibb, Convelo, EMD Serono Inc, FiND, INMune, and Sandoz. Dr. Obeidat has financial relationships with Alexion Pharmaceuticals, Banner Life Sciences, BD Biosciences, Biogen, Biologix Solutions, Bristol Myers Squibb, Celgene, EMD Serono, Genentech, GW Pharmaceuticals, Horizon Therapeutics, Jazz Pharmaceuticals, Novartis, Sandoz, Sanofi Genzyme, TG Therapeutics, and Viela Bio. Ms. Ross has consulted for EMD Serono, BMS, Horizon, Alexion, TG Therapeutics, Novartis, Roche, and Sanofi.
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<root generator="drupal.xsl" gversion="1.7"> <header> <fileName>168382</fileName> <TBEID>0C050813.SIG</TBEID> <TBUniqueIdentifier>MD_0C050813</TBUniqueIdentifier> <newsOrJournal>News</newsOrJournal> <publisherName>Frontline Medical Communications</publisherName> <storyname>CMSC: Ocrelizumab pediatric dose</storyname> <articleType>2</articleType> <TBLocation>QC Done-All Pubs</TBLocation> <QCDate>20240612T131220</QCDate> <firstPublished>20240612T161114</firstPublished> <LastPublished>20240612T161114</LastPublished> <pubStatus qcode="stat:"/> <embargoDate/> <killDate/> <CMSDate>20240612T161114</CMSDate> <articleSource>FROM CMSC 2024</articleSource> <facebookInfo/> <meetingNumber>5111-24</meetingNumber> <byline>Jim Kling</byline> <bylineText> JIM KLING </bylineText> <bylineFull> JIM KLING </bylineFull> <bylineTitleText>MDedge News</bylineTitleText> <USOrGlobal/> <wireDocType/> <newsDocType>News</newsDocType> <journalDocType/> <linkLabel/> <pageRange/> <citation/> <quizID/> <indexIssueDate/> <itemClass qcode="ninat:text"/> <provider qcode="provider:imng"> <name>IMNG Medical Media</name> <rightsInfo> <copyrightHolder> <name>Frontline Medical News</name> </copyrightHolder> <copyrightNotice>Copyright (c) 2015 Frontline Medical News, a Frontline Medical Communications Inc. company. All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>In pediatric multiple sclerosis (MS), the optimal dose of ocrelizumab is the same as the 600 mg adult dose for patients weighing more than 35 kg</metaDescription> <articlePDF/> <teaserImage/> <teaser>Pharmacokinetic and pharmacodynamic data show that adult dose is safe and effective for most children.</teaser> <title>Pediatric Ocrelizumab Dose Established for MS</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear>2024</pubPubdateYear> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>nr</publicationCode> <pubIssueName>January 2021</pubIssueName> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> <journalTitle>Neurology Reviews</journalTitle> <journalFullTitle>Neurology Reviews</journalFullTitle> <copyrightStatement>2018 Frontline Medical Communications Inc.,</copyrightStatement> </publicationData> <publicationData> <publicationCode>msrc</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> <journalTitle/> <journalFullTitle/> <copyrightStatement/> </publicationData> </publications_g> <publications> <term canonical="true">22</term> <term>59347</term> </publications> <sections> <term canonical="true">53</term> <term>39313</term> </sections> <topics> <term canonical="true">251</term> </topics> <links/> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Pediatric Ocrelizumab Dose Established for MS</title> <deck/> </itemMeta> <itemContent> <p><span class="dateline">NASHVILLE, Tennessee </span>— <span class="tag metaDescription">In pediatric multiple sclerosis (MS), the optimal dose of ocrelizumab is the same as the 600 mg adult dose for patients weighing more than 35 kg</span>, according to pharmacokinetic/pharmacodynamic (PK/PD) data from the OPERETTA 1 phase 2 clinical trial. The safety profile was similar to adult patients. </p> <p>“While we believe the disease to be the same in children and adolescents, [MS] is distinguished by its very inflammatory nature, oftentimes causing two to three times the number of relapses per year as their adult-onset colleagues,” said Teri Schreiner, MD, during a presentation of the results at the annual meeting of the Consortium of Multiple Sclerosis Centers.<br/><br/>Approved therapies for pediatric MS include fingolimod in the United States and Europe, as well as dimethyl fumarate in Europe. “There’s a real need for high-efficacy treatment [in pediatric patients], again referring back to this disease being very inflammatory in children and adolescents. We oftentimes will use medications off label but this is clearly suboptimal as we lack safety data, and oftentimes run into difficulty with insurance approval of off-label use of medicine,” said Dr. Schreiner, who is an associate professor of neurology at University of Colorado School of Medicine, Aurora. <br/><br/>To determine the dose in pediatric patients that would produce comparable PK and PD to adults, the researchers dosed six patients aged 10-18 with 300 mg ocrelizumab, and 17 such patients with 600 mg ocrelizumab during a 24-week dose-exploration period, followed by a 264-week optional extension period. The cohorts were separated based on weight of less than or more than 40 kg. The mean ages were 11.2 years (mean weight, 34.9 kg) and 15.3 years (mean weight, 62.3 kg), respectively. <br/><br/>During the dose-exploration period, seven blood draws were performed to characterize PK. “When the PK data was analyzed, we saw that the proper cut-off point was 35 kilos. At less than 35 kilos, the appropriate dose was half of that adult dose, so 300 milligrams every 6 months, whereas above 35 kilos, the proper dose was actually 600, or the adult dose. Given the rarity of pediatric-onset MS patients less than 35 kilos, most patients will benefit from the adult dose of 600 milligrams twice yearly,” said Dr. Schreiner. <br/><br/>PD data were also encouraging. “The primary PD was the absence of CD-19 B cells, and that was tracked over time. While there were a few patients in both cohorts that had modest reconstitution, there was no patient in our study that crossed the retreatment threshold, and all blood samples were negative for anti-drug antibodies,” said Dr. Schreiner. <br/><br/>Adverse events occurred in five of six patients in the 300 mg group (83%; 4 grade 2, 1 grade 3) and 100% of patients in the 600 mg group (1 grade 1, 9 grade 2, 6 grade 3, 1 grade 4). There was one serious adverse event in the 300 mg group (16.7%) and four serious adverse events in the 600 mg group (23.5%). None led to treatment discontinuation. “This is largely consistent with what was seen in the adult studies of ocrelizumab,” said Dr. Schreiner. <br/><br/>Roche is now recruiting for the phase 3 <span class="Hyperlink"><a href="https://www.operetta2.com/">OPERETTA 2 trial</a></span>, which will use the 600 mg dose and compare outcomes to a fingolimod arm. <br/><br/></p> <h2>Establishing Safety in the Pediatric Population</h2> <p>“In [pediatric onset MS] it’s an important piece of information to design OPERETTA 2 and to dose ocrelizumab in pediatric-onset MS in general,” said Jeffrey A Cohen, MD, professor of neurology at the Cleveland Clinic, who was asked for comment.</p> <p>During the Q&A period, Dr. Schreiner was asked whether it is possible to extrapolate experience from rituximab to the pediatric population. “They’re very similar molecules, and we know the mechanisms of action, but I think part of the importance of doing these studies is to get the safety data so that we actually can say with certainty, we are giving you a drug that has this list of side effects and we know about them definitively. We all use other high-efficacy medications, but I don’t think we can exactly extrapolate,” said Dr. Schreiner. <br/><br/>Session moderator Amy Perrin Ross, APN, noted the lack of approved pediatric therapies for MS. “This is an extremely important study, because we at least in the lower 48 are quite limited in our resources for approved pediatric cases. Information like this will make it easier for a potential pediatric indication, which would then make it easier on us to go after [treatment of the disease in this population]. The weight-based dosing, I think, is really a good thing. Patients have been asking for weight-based dosing on everything for many years,” she said.<br/><br/>Ahmed Obeidat, MD, PhD, associate professor at the Medical College of Wisconsin, also praised the study. “While pediatric MS is rare, it is an area of unmet need when it comes to disease-modifying therapies as only fingolimod is FDA-approved, and many use B cell–depleting therapy, such as rituximab, off label to treat children with MS with good outcomes. The need for guidance on the dosing of B cell–depleting therapy is a main priority for research in pediatric MS,” he said.<br/><br/>The study was funded by Roche. Dr. Schreiner has consulted for Roche and Cycle Pharmaceuticals. Dr. Cohen has consulted for Astoria, Bristol Myers Squibb, Convelo, EMD Serono Inc, FiND, INMune, and Sandoz. Dr. Obeidat has no relevant financial disclosures. Ms. Ross has consulted for EMD Serono, BMS, Horizon, Alexion, TG Therapeutics, Novartis, Roche, and Sanofi.<span class="end"/></p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> </itemSet></root>
FROM CMSC 2024