In 2017, drug maker Genentech completed a Phase 3 trial with their drug Ocrevus for treating primary progressive multiple sclerosis (PPMS). They named the Study “ORATORIO”. As the name implies, PPMS worsens continually in the patient, without remissions, which are present in the more common relapse/remitting form of MS (RRMS).
For the trial, a group of 244 patients visited medical offices around the world for two treatments every six months. They had been diagnosed with PPMS for an average of 1.5 years, though they’d had symptoms for 5 or 6 years on average.
For each treatment, an IV needle was inserted into the patient’s arm, and medicine dripped for hours into their veins. To pass the time, they read, snoozed, or surfed the web on their cell phones. The lucky ones were served snacks or lunch. Most were given steroids to prevent reactions from the treatment.
They were treated for an average of 2.7 years. At the end of the trial, an astonishing 61% of patients had suffered no symptom progression. Imagine how that 61% must have felt. Hopeful? Lucky? Excited? Ocrevus was a miracle drug!
I’ve left out a small detail. Those 244 patients were the placebo group of the study, and their “drug” infusions were saline solutions.
The patients weren’t aware of this, of course, since the Study was “double blind”, meaning neither they nor their doctors and nurses knew what was in the liquid that they were being injected with.
Now, let’s turn to the group of 487 patients who actually received Ocrevus during the trial. 67% of this group were lucky enough not to encounter disease progression during the Study. So, we can estimate Ocrevus was effective for 6% of those, while the other 61% would not have progressed anyway, just like the placebo group.
Why did so many people fail to progress in both groups? Well, PPMS is in some ways a slow moving disease. It takes 2-3 years, depending on the data set you look at, for disability to increase by one point on the 10-point EDSS (Expanded Disability Status Scale). And for disease progression to count in the Study, a patient must have increased by 1 point on the EDSS if he or she started with an EDSS of less than 5.5, or .5 points if starting with an EDSS above 5.5. The median patient EDSS was 4.5, so the majority of patients had to increase their score by a full point to “qualify” for progression.
The moral here, is that if you’ve been taking Ocrevus for PPMS for two or three years, and your progression hasn’t increased significantly, it’s worth remembering that 61% of people on the placebo in the ORATORIO study had the same experience. If you’re feeling better, it may well be the Ocrevus. But the Study tells is that odds are it’s just the placebo effect.