A year after U.S. regulators approved Genentech’s Ocrevus (ocrelizumab) as the first treatment for both the relapsing and progressive forms of multiple sclerosis, a prominent neurologist involved in the Phase 3 clinical trials that led to its authorization says it has been beneficial for some MS patients.
But it’s simply too early to tell if the infusion therapy is the game changer its developers predicted it could be for the MS population in general, he said.
The U.S. Food and Drug Administration approved Ocrevus on March 28, 2017 — a milestone, considering that MS is now believed to affect nearly one million people in the U.S., according to the CMSC.
“It’s too soon to say anything. We usually look at patients who were followed for two years in the blinded portion [of a trial] and then in open-label extensions,” Lisak told MS News Today in a phone interview.
“Given that, I can say that quite a few patients, in my experience, who were doing poorly on other medications and then switched to ocrelizumab seem to be doing well,” he said. “Among patients who were not doing well with breakthrough attacks or imaging abnormalities, a lot of them seem to have stopped having attacks.”
Hope for PPMS patients
In clinical trials, Ocrevus — which is administered as an intravenous infusion once every six months — slowed MS progression. This has given hope to the thousands who suffer from primary progressive multiple sclerosis (PPMS) and the more common relapsing-remitting (RRMS) form of the disease.
About 15 percent of all MS patients are believed to have PPMS, which in general is more difficult than RRMS to diagnose and treat. People with PPMS also tend to have more difficulty walking, and usually require more assistance with everyday activities.
“We have a huge number of patients that have sort of been waiting in the wings for some therapy for PPMS,” Lisak said. “But one year of progression is very difficult to judge, and to say before two years what’s going on is impossible.”
He added, however, that “you don’t really know how a therapy is doing in an individual patient unless they were doing terribly and are now doing very well, or they’re now doing poorly.
“With in-between patients, it’s difficult to know whether you’re getting a partial response,” he said.
“The patient who seems to be stable may have a mild attack every two or three years, or no new [brain] lesions. In that case, you don’t know what they would have done had you not put them on any new therapy,” Lisak said. “Suppose you had decided to switch them off Rebif. If they do spectacularly well, then Ocrevus has been a big improvement. But if they were doing OK on Rebif or Copaxone, and you then switch them to Ocrevus and they’re still doing the same or a little better, you can’t tell.”
Brain lesions are areas where the myelin sheath that protects nerve cells has deteriorated. It’s a hallmark of MS.
Another group of patients that have done well on Ocrevus are those who were previously doing well with Tysabri, but switched because of concerns with or evidence of JC virus, which can lead to a potentially fatal brain inflammation known as progressive multifocal leukoencephalopathy (PML). Tysabri treatment is known to increase the risk of PML.
Insurance not a major problem
Lisak said access to the $65,000-a-year Ocrevus varies according to a patient’s insurance company, but most insurers have covered it after other therapies failed.
“The only problem we’ve had occasionally is when a patient has such active disease and such poor indicators that you’d like to put them on Ocrevus or Tysabri right from the beginning,” he said. “We have had a lot of resistance from insurance companies. But as a second- or third-line treatment, when a patient has failed or doesn’t tolerate another drug, we’ve done pretty well.”
“Knock on wood,” was Lisak’s response when asked about safety issues linked to Ocrevus.
“So far, there have been no tumors or opportunistic infections, but it’s only a year,” he said. “You don’t know you’re out of the woods yet. The extension study of ORATORIO and OPERA 1 and 2 have looked reasonably good, but you don’t know what’s going to come five years out.”
The biggest worry, he said, is a possibly heightened risk of breast cancer among women on Ocrevus. In clinical trials, half a percent of patients with relapsing MS and 2.3 percent of PPMS patients developed cancer. Genentech urges women on therapy to undergo routine breast cancer screening based on age and family history of cancer.
“It’s a concern until we see statistics one way or another,” Lisak said, noting that none of the patients on a placebo during the Ocrevus trials developed the disease.
“Unless you think placebo prevents breast cancer, you’ve got to worry about it,” he said. “We have a lot of patients who, when they hear that there’s a risk and they have a family history, they shy away from it. So you’re sort of self-selecting out the patients who might be more likely to get breast cancer.”
Twice-a-year infusions and stability
Lori Mayer is director of medical research at Central Texas Neurology Consultants in Austin.
A registered nurse, she was involved in clinical trials of Ocrevus. She works with Edward Fox, a top neurologist studying MS.
“I think the efficacy data speaks for itself in that what you see in the clinical trials is what we see in real life,” Mayer said. “Many are patients who were on treatments maybe every day — either a pill or an injectable — or maybe a couple of times a week.”
The infusion method of delivery causes some patients to feel as if they’re not doing anything to fight their disease, she said. But Ocrevus is effective for six months.
“Patients have to readjust their mindset that they’re still doing something for their MS, but that they don’t have to think about it for six months. It’s kind of psychological, but it’s a very important component,” Mayer said.
“Every MS patient has his or own variety of symptoms, and these fluctuate from day to day, from morning to night, and from month to month. There’s no continuity of anything.
“What I see with these patients on Ocrevus is that they don’t [have to] deal with this,” she said. “They have more stability, and for them, that makes a significant difference. When patients don’t need to think about their MS on a daily basis, their whole life changes.”
That translates into an improved quality of life for that patient, Mayer said. About 200 of the 1,400 patients being treated at her clinic are receiving Ocrevus.
“The PPMS population is small, compared to RRMS, but those progressive patients that are on Ocrevus are really excited because there hasn’t been a disease-modifying therapy available for them in the past. This is the first FDA-approved treatment for progressive MS.”
She said the four-hour infusion required for Ocrevus is tolerated “really well,” and that its disadvantages are limited.
“There is some concern about breast cancer issues, since so many of our patients are women,” she said, echoing Lisak’s concerns. “That’s where your long-term safety evaluations really come in, and we need to follow them over time.”
Mayer said her clinic recommends that women follow the American College of Obstretricians and Gynecologists’ mammogram advice, and tells patients that vaccines need to be done at least six weeks before an Ocrevus treatment begins.
The CMSC will soon issue specific guidelines to patients considering this therapy, she added.