One of the next new kids on the block is going to be Ofatumumab (Anti-CD20). There were positive data on the MRI scans and on relapse rate that puts it in the league of the big hitters. This is hardly surprsing as it is a Me-Too drug and does the same as rituximab and ocrelizumab. This data was shown at Ectrims2019 in the ASSCLEPIOS (Greek god of healing) trials. OPERA was the trial name for ocrelizumab (anti-CD20).
So it seems we are going classical with the trial names as they are not an acronymn. But next year we will ge the phase III results of ublituximab (Anti-CD20) in the ULTIMATE trial…I wonder if this is the Greek god of Banking, as I am sure I can hear “Show me the money” as Pharma can scent the cash of following in the footsteps of others. We are now having a glut of Mods, we will soon have a glut of anti-CD20 antibodies.
Ofatumumab will be the first fully human antibody to hit the stands and is given monthly by subcutaneous injection. When asked what would Prof Hauser advise being the leader of the pack with ocrelizumab and now ofatumumab, he seemed to indicate it depends how forgetful you are:-). Do you fancy that hospital outing or stay at home for a self-injection?
However, whilst the data was impressive compared to teriflunomide, it is hardly surprising that ofatumumab beats teriflunomide. It was markedly effective at blocking relapses (ARR = 0.1) and MRI inhibited.
However, this is where Prof G pipes up what about the brain atrophy data and here it didn’t win. Prof Hauser says that’s because teriflunomide outperforms on brain atrophy but hey look at the neurofilament data there is highly significant benefit in neurofilament light loss with ofatutumumab.
Now you ask why select a competitor that you think you could lose against? That’s a question for the manufacturer.
You could also ask. Why not go head to head against the licensed anti-CD20? However, that would be commercial suicide if you lost.
Now I must say something. You can’t have it both ways. Teriflunomide was not that effective on neurofilament light loss…..so how can it be claimed it is so effective in brain atrophy change, if a common mechanim is at work here?
This I think occurs, because neurofilament is responding to inflammation induced nerve damage rather than the nerve loss driving the progressive atrophy. Therefore the brain atrophy and the neurofilament is measuring differnt things. Therefore neurofilament light is a surrogate of MRI activity and not progressive neurodegeneration that is not associated with active disease. We know that natalizumab is great at dropping neurofilament light levels too. This was also supported by that seen in the PROXIMUS trial of sodium channel blocker + disease odifying drug.
If you are a neurologist and want neurofilament levels tested contact NDG for details
I suspect that ProfG will have something to say on this and again the brain atrophy seen with ofatumumab is not in the ball park seen with alemtuzumab in its pivotal trial. Many neurologists will just see this headline result. Indeed maybe the extra depletion of T cells is the key. However, in this trial the median time from diadgnosis was about 8-9 years, which is about the same as cladribine, but 5-7 years later than the alemtuzumab trials. Is this the difference? I think this is possible. The brain atrophy data was about -0.6 in the CLARITY trails (8-9 years from diagnosis) compared to 0.2 in the ORACLE trial (0.5 year from diagnosis), which is about the rate of natrual aging and the same as seen with alemtuzumab (CARE-MS I. 2 years from diagnosis)
Maybe they need to do some studies in early MS and get to the bottom of this. Maybe if ProfG can do a DoDo ocrelizumab trial where you compare a high dose to a standard dose, it should be done ASAP after diagnosis and work it out if age and disease-duration is the difference. This could be well be the battle ground where you try and decide which treatment to use as they are very similar in their ability to inhibit relapse. Which anti-CD20 best inhibits brain atrophy. Will a low-dose injected into the skin, get into the brain verses a much higher dose given as an infusion. Is this where ocrelizumab takes on rituximab?
You can watch the session on the ECTRIMS2019 website
Much of what I learned about anti-CD20 was from talking to neurologists using the different formulations and dosing regimes. I didn’t know that some people were already using ofatumumab (human Ig) when rituximab (Chimeric mouse/human) had failed because of neutralizing antibodies. However, I know wonder if the cancer formulation has a limited lifespan when will it be canned to make way for the expensive MS drug. Would that be in the spirt of Assclepios or is that why he appears with a snake?