We recently had a post where the FDA was starting to question the data from the ORATORIO trial and British Medical Journal suggested that the data was fudged and that the women in the trial got no/less efficacy and that they got a risk of breast cancer which had occurred in the trial. I thought that the ORATORION-Hand Trial would counter this claim. I pinged him an email and “yep” was the answer.
Many years ago ProfG had the idea that rather than simply focusing on lower limb (leg) function as an outcome for trials we should look at the upper limb (arm) as an endpoint as it may not be too late to save function in the arm when leg function has been lost. The “Think-Hand” idea was generated within the team and it was part of the Chariot-MS trials to get drugs into people with advanced MS, with the view that it should never be too late to try and save remaining nerve function. ProfK got support from to do this study but Prof-G took the easier route and encouraged pharma to do the studies and to lobby the regulators to view things other than the EDSS as an outcoem. Oratario-Hand or O-hand as we know it was born from the ideas. We went round the Excel Centre in London at ECTRIMS with ballons that read “95%” it was based on the view that when asked about saving leg or hand function, 95% of the respondants picked hand function. This seems like eons ago but the trial was done and it was a success and if this view had been adopted years ago we would have treatments for progression decades ago. This has been talked about at other meetings but is getting a new viewing in Chicago. Given that it is starting today and it is apt to question the wisdom of the FDA. Here is ProfGs post on MS-selfie
“The banter around yesterday’s Q&A on whether or not ocrelizumab’s license for treating PPMS should be revoked has been quite interesting. It is worth reading the comments and the responses to them. All of this is in response to the news piece, albeit out-of-date, published by the BMJ.
It is quite amazing how some people can’t move forward when new information becomes available that confirms and/or reinforces prior information, creates new information, adds more context and changes the narrative. This prompted me to quote John Maynard Keynes: “When the facts change, I change my mind – what do you do, sir?”
Let’s hope the debate over the effectiveness of ocrelizumab in primary progressive MS will be settled once the O’HAND data are published and submitted to the FDA and other regulators.
The good news for me is that the American Academy of Neurology has just recognised our abstract for the O’HAND study for distinction. At least my colleagues in the American neurological community acknowledge the importance of this study.”
Here is the Abstract from the AAN 2026 meeting
ORATORIO-HAND: Results of the Primary Analysis of Ocrelizumab vs Placebo in Primary Progressive Multiple Sclerosis, Including Older Patients and Those With More Advanced Disease
Gavin Giovannoni1, Laura Airas2, Riley Bove3, Gary Cutter4, Jeremy Hobart5, Jens Kuhle6, Xavier Montalban7, Carmen Tur8, Jerry Wolinsky9, Hans-Martin Schneble10, Anna Baldinotti10, Ulrike Bonati10, Caroline Giacobino10, Qing Wang10, Ke Yang10, Jiwon Oh11
1Department of Neurology, Royal London Hospital, Barts Health NHS Trust, London, UK and Blizard Institute, Queen Mary University, London, UK, 2University of Turku, Turku, Finland, 3UCSF Weill Institute for Neuroscience, Department of Neurology, University of California San Francisco, San Francisco, CA, USA, 4The University of Alabama at Birmingham, School of Public Health, Birmingham, AL, USA, 5Peninsula Medical School, Plymouth University, UK, 6MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel, University of Basel, Basel, Switzerland, 7Centre d’Esclerosi Múltiple de Catalunya, Vall d’Hebron University Hospital, Barcelona, Spain, 8Queen Square MS Centre, Department of Neuroinflammation, Institute of Neurology, Faculty of Brain Sciences, University College London (UCL), London, UK/Neurology-Neuroimmunology Department, Multiple Sclerosis Centre of Catalonia (CEMCAT), Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain, 9Department of Neurology, University of Texas Health Science Center, Houston, TX, USA, 10F. Hoffmann-La Roche Ltd, Basel, Switzerland, 11Division of Neurology, Department of Medicine, St. Michael’s Hospital, University of Toronto, Toronto, Ontario, Canada
Objective:ORATORIO-HAND (NCT04035005) evaluated the efficacy and safety of ocrelizumab in patients with primary progressive multiple sclerosis (pwPPMS), including older pwPPMS and those with more-advanced disease.
Background: ORATORIO (NCT01194570) showed superiority of ocrelizumab vs placebo in delaying disability progression in pwPPMS. The impact of ocrelizumab in older and more-advanced pwPPMS is not fully understood, particularly in preventing hand-function worsening.
Design/Methods:Adult pwPPMS (≤65 years, Expanded Disability Status Scale [EDSS] score: 3.0-8.0) were randomized 1:1 to ocrelizumab 600 mg or placebo every 6 months for 144 weeks or until ≥340 progression events, whichever occurred earlier. The primary endpoint was a composite of time to onset of 12-week confirmed disability progression (12W-cCDP) in 9-Hole Peg Test (CDP-9HPT ≥20% worsening from baseline) or EDSS (CDP-EDSS) in all randomized and a subset of MRI-active patients.
Results:In ocrelizumab (n=505) and placebo (n=508) patients, baseline median (range) age was 48 (18-66) vs 47 (22-66) years and EDSS was 6.0 (3.0-8.0) vs 6.0 (2.5-8.0); median treatment duration was 144.0 and 143.7 weeks. The percentage of ocrelizumab and placebo patients with 12W-cCDP was 32.7% vs 40.4% (hazard ratio [HR] [95% CI]: 0.70 [0.57-0.86]; risk reduction [RR], 30%; P=0.0007); 16.7% vs 24.9% on 9HPT (RR, 41%; P=0.0002) and 23.0% vs 30.8% on EDSS (RR, 33%; P=0.0013). In the MRI-active subset, the percentage of patients with 12W-cCDP was 26.8% vs 45.9% (HR [95% CI]: 0.45 [0.31-0.64], RR, 55%; P<0.0001), with significant RRs observed in CDP-9HPT (62%) and CDP-EDSS (59%). The safety profile was similar between both arms, apart from infusion-related reactions (20.8% ocrelizumab vs 4.3% placebo) and infections (48.4% vs 44.7%). Additional results will be presented.
Conclusions: In pwPPMS including those with more-advanced disease, ocrelizumab was superior to placebo in delaying overall disability progression and upper-limb–function worsening. Adverse events reported were consistent with the known ocrelizumab safety profile.
I am sure ProfG will be asking for the slide that shows that Women respond and there was not a breast cancer signal….Wasting your time FDA?
Part of the O-Hand thought process comes from seeing the meeces they lose tail function first then lower leg function and then upper leg function. In the meeces function of the front legs seldom occurred and it was an “humane” endpoint if that occurred.
COI Multiple
Disclaimer My views and a cut and Paste from ProfG’s website…check it out.
Source: multiple-sclerosis-research.org