Ocrevus May Delay by 7 Years PPMS Patients’ Need for Wheelchair

Ocrevus (ocrelizumab) treatment may delay the need for a wheelchair by seven years in patients with primary progressive multiple sclerosis (PPMS), a study reports. This delay, drawn from clinical trial data on treatment- versus placebo-group patients and supported by real-world findings, likely translates to long-term benefits for PPMS patients,…

Trial to Examine if Ocrevus Eases Cognitive Fatigue in RRMS

Researchers at the Kessler Foundation, with support from Genentech, are opening a study into how Ocrevus (ocrelizumab) affects cognitive fatigue — the feeling of complete exhaustion after focused concentration — in people with relapsing-remitting multiple sclerosis (RRMS). Cognitive fatigue is a frequent problem with MS, reported in…

Ocrevus Use Still Growing in Europe But Challenges on Horizon, Spherix Reports

Prescriptions of Roche’s Ocrevus (ocrelizumab) among multiple sclerosis (MS) patients initiating or switching a disease-modifying therapy (DMT) continue to rise in Europe, according to a survey conducted by Spherix Global Insights. Ocrevus, an anti-CD20 monoclonal antibody administered directly into a vein, was approved in the European Union to treat active forms…

Scottish Medicines Consortium Approves Ocrevus for Treating PPMS

Ocrevus (ocrelizumab) has been approved in Scotland as a treatment for early, inflammatory primary progressive multiple sclerosis (PPMS). The Scottish Medicines Consortium (SMC) has advised that Ocrevus can be prescribed by the National Health Service (NHS) for people with PPMS who have had symptoms for less than 15…

Ocrevus Increases Proportion of PPMS Patients with No Disease Progression or Activity, Phase 3 Trial Shows

Treating primary progressive multiple sclerosis patients with Ocrevus (ocrelizumab) led to a three-fold increase in the proportion of those showing no evidence of disease progression and no signs of inflammatory disease activity over more than two years of treatment, results of a Phase 3 trial show, and support new measures that might better capture disability in PPMS patients. The research, “Evaluation of No Evidence of Progression or Active Disease (NEPAD) in Patients With Primary Progressive Multiple Sclerosis in the ORATORIO Trial,” was published in the journal Annals of Neurology. Measuring disease progression in clinical trials and clinical practice requires reliable and comprehensible measures. Although widely used, the Expanded Disability Status Scale (EDSS, range 0-10) cannot fully capture changes in walking speed and hand or arm function, which are key determinants of overall disability in progressive forms of MS. No evidence of progression (NEP) is a newer measure that reflects the absence of disability progression, including upper limb function and walking speed. Maintaining NEP status means stable disease with no worsening in EDSS, in walking ability (assessed by the Timed 25-Foot Walk (T25FW) test, or the time it takes to walk 25 feet as quickly and safely as possible), and in upper limb function (assessed by the 9-Hole Peg Test (9HPT), a test of arm and hand dexterity). Patients with PPMS have less frequent signs of disease activity, which include relapses and brain lesions (assessed though magnetic resonance imaging or MRI). So scientists proposed a new measure — called “no evidence of progression or active disease” (NEPAD) — to evaluate both NEP and clinical and MRI measures of active disease. The researchers believe that NEPAD may represent a more sensitive and comprehensive measure of disease control in PPMS patients. The randomized, double-blind ORATORIO Phase 3 trial (NCT01194570) analyzed the efficacy and safety of Ocrevus — developed by Genentech, part of the Roche group — in 732 PPMS patients (age range 18–55). Results showed that Ocrevus treatment delayed the relative risk of disability progression by 25% compared to placebo, while also reducing the volume of chronic brain lesions and total brain volume loss. As a result, Ocrevus became the first therapy approved by the U.S. Food and Drug Administration and the European Commission for both PPMS and relapsing MS. Now, researchers assessed Ocrevus’ effect in PPMS patients included in the Roche-funded ORATORIO study using as trial goals changes in NEP and NEPAD. These people received either 600 mg of Ocrevus or placebo by intravenous (IV) infusion every six months for a minimum of 120 weeks (about 2.3 years). The trial’s main goal was time to onset of clinical disability progression (CDP) sustained for at least 12 weeks. CDP was defined as a 1.0 point or greater increase in EDSS score from a baseline (study start) score of 5.5 or less, or a 0.5-point increase from a baseline score greater than 5.5. NEP status, analyzed in 230 placebo- and 461 Ocrevus-treated patients, was defined as no evidence of CDP for 12 weeks, no 20% or more change in hand/arm function as measured by the 9HPT for 12 weeks, and no 20% or more change in walking ability as measured by the T25FW test for 12 weeks. "The 20% cut-off for progression on the T25FW test and the 9HPT has previously been shown to be a clinically meaningful magnitude of disease progression," the study noted. In turn, NEPAD — assessed in 234 placebo- and 465 Ocrevus-treated patients — included NEP, no brain MRI-measured disease activity, and no relapses. Relapses were defined as new or worsening neurological symptoms attributable to MS lasting longer than 24 hours and preceded by neurological stability for a minimum of 30 days. Brain MRI scans were conducted at baseline, and weeks 24, 48, and 120; new or enlarging T2 lesions and/or T1 enhancing lesions were considered evidence of MRI disease activity (T1 MRI imaging offers information about current disease activity by highlighting areas of active inflammation, while a T2 MRI image provides information about disease burden or lesion load). Overall, the majority of the PPMS patients analyzed experienced clinical disease progression or evidence of disease activity. From baseline to week 120, Ocrevus-treated patients who achieved NEP (42.7% of 461 people) or NEPAD (29.9% of 465)  — no disease activity or progression — were found to have lower T2 brain lesion volume and a lower EDSS score (lesser disability) compared to those with evidence of MS progression. They also had a slightly superior performance on the 9HPT and the T25FW test. Patients who reached NEPAD also showed fewer T1 lesions than patients with progressing or active disease. Compared to placebo treatment, the proportion of Ocrevus-treated PPMS patients maintaining NEP or NEPAD from baseline to week 120 was higher — for NEP, 42.7% versus 29.1% in the placebo group; for NEPAD, 29.9% versus 9.4% in the placebo group. These results showed that Ocrevus treatment increased the proportion of PPMS patients with NEPAD throughout the 120 weeks of the study by three-fold. “In conclusion, ocrelizumab (Ocrevus) increased the proportion of patients with PPMS with no evidence of progression and no clinical and subclinical disease activity compared with placebo,” the team wrote. “As such, NEPAD may represent a meaningful and comprehensive disease outcome in patients with PPMS.” However, data from ORATORIO's open-label extension and real-world data are needed to "determine whether NEPAD maintained throughout 120 weeks will translate into sustained NEPAD and enhanced protection against accrual of disability in patients with PPMS over the long term," the researchers concluded. Of note, five of the study’s 11 authors are employees and/or shareholders of Roche or Genentech.

#AAN2018 — Ocrevus Lowers Immune Response to Vaccines in Relapsing MS, Phase 3 Trial Shows

Treatment with Ocrevus (ocrelizumab) is linked to a reduced immune response to vaccinations in patients with relapsing multiple sclerosis (MS), according to a Phase 3 trial. These results were recently presented at the 2018 American Academy of Neurology (AAN) Annual Meeting in Los Angeles in a presentation titled, “Effect of Ocrelizumab on Vaccine Responses in Patients With Multiple Sclerosis.” Genentech’s Ocrevus is an approved MS therapy that targets the CD20 protein located on the surface of B-cells, targeting the cells for destruction. B-cells are immune system cells involved, for example, in the production of antibodies necessary to fight off infection. At the AAN meeting, researchers reported that in MS patients, treatment with Ocrevus decreased the ability of B-cells to activate other immune cells, improving the rate of MS attacks. Penn Medicine neurologist Amit Bar-Or, MD, presented these findings, which showed that interactions between different classes of immune cells, such as B- and T-cells, promote MS attacks. Vaccination against infections is an important part of the management of patients with MS. So, in a second study (NCT02545868), researchers investigated the impact treatment with Ocrevus has on patient response to vaccines. They recruited 102 patients with relapsing MS and randomized them in two groups. In group A, 68 people received a single dose of 600 mg Ocrevus (administered into the blood); in group B, 34 patients received no disease-modifying therapy or interferon-beta. All patients were then administered vaccines for tetanus, seasonal flu, and pneumococcus. Patients in group A received the vaccines 12 weeks after they were treated with Ocrevus, while group B patients received the vaccines on day one. Researchers also tested patients’ response to a novel protein (an antigen) never "seen" by their immune system, called keyhole limpet hemocyanin (KLH) neoantigen. The vaccinations led to an immune system response in all patients, but the level of response in patients treated with Ocrevus was lower. A positive response to the tetanus vaccine at eight weeks after treatment was 23.9% in group A (Ocrevus) compared with 54.5% in group B (no treatment); the response to pneumococcus vaccination was 71.6% in group A and 100% in group B. After four weeks of treatment, the levels of antibodies against the different strains of the flu virus were lower in Ocrevus-treated patients than in the control group, ranging from 55.6% to 80.0% in the Ocrevus group compared with 75.0% to 97.0% in the controls. The immune response to the neoantigen KLH was also decreased in the Ocrevus group. "This study shows that while people with MS treated with ocrelizumab [Ocrevus] can still mount vaccine responses, it's not nearly as strong as prior to treatment," Bar-Or said in a press release. "While antibody responses were reduced in the ocrelizumab treated patients, they still responded to a certain level," he said. "This is valuable information in terms of seasonal vaccines such as the flu — it appears safe for patients taking ocrelizumab to get vaccinated and vaccination is likely to provide them with at least some protection from such infections." These findings correlate with standard guidelines that advise patients to undergo vaccinations six weeks before they start treatment with Ocrevus.

#AAN2018 – Ocrevus Decreases Biomarkers of MS Patients’ Nerve Cell Damage, Phase 3 Trial Shows

Genentech’s Ocrevus (ocrelizumab) reduces levels of cerebrospinal fluid biomarkers that denote nerve cell damage in multiple sclerosis patients, a Phase 3 clinical trial shows. Researchers will present the results at the American Academy of Neurology’s annual meeting in Los Angeles, April 21-27. The presentation will be titled “Interim Analysis of the…

5 MS Patients Across US Talk About How Ocrevus Has Changed Their Lives

It’s been a little over a year since U.S. regulators approved Genentech’s Ocrevus (ocrelizumab) as the first treatment for both relapsing and progressive forms of multiple sclerosis (MS) — a disabling neurological disease now believed to affect nearly one million Americans. While the jury’s still out regarding the therapy’s…

An Ocrevus Update Has Me Cautiously Optimistic

After a delay in treatment in late December thanks to a nasty head cold, and the after-effects of contracting the flu in February necessitating another delay, I finally received my second six-month dose of Ocrevus (ocrelizumab) in mid-March. Much like the first time, the infusion was uneventful. I had no…

Ocrevus a Year After Approval: Views of Some MS Experts

A year after U.S. regulators approved Genentech's Ocrevus 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 a godsend for certain subsets of 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 neurologist, Dr. Robert Lisak, who is past president of the Consortium of Multiple Sclerosis Centers (CMSC), teaches immunology and biology at Detroit’s Wayne State University School of Medicine. 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. 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 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. Dr. Robert Lisak estimates that 500 to 600 of the several thousand MS patients being treated at his Detroit clinic are receiving Ocrevus. But he points out 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.

It Shouldn’t Be This Hard to Get Our MS Medications

I got a phone call from my MS One to One nurse, Lynn, today. One to One is the patient support service provided by Sanofi Genzyme for patients on the biotech company’s MS disease-modifying therapies (DMTs) Lemtrada (alemtuzumab) and Aubagio (teriflunomide). Lynn called to ensure that all…

New Ocrevus Data, Post-FDA Approval, Supports Range of Benefits, Genentech’s Hideki Garren Says

Ocrevus (ocrelizumab), Genentech’s humanized anti-CD20 monoclonal antibody, continues to show clear evidence that it helps to slow disease progression and enable better function — including in the hands and limbs — of relapsing multiple sclerosis (MS) and primary progressive multiple sclerosis (PPMS), latest data reveals. The first FDA-approved therapy — in March…

#ACTRIMS2018 – Relapsing MS Patients With Impaired Vision Improved on Ocrevus, Updated Trial Data Show

Ocrevus improved vision among relapsing multiple sclerosis patients who participated in the Phase 3 clinical trials of the treatment, according to updated analyses recently presented at the ACTRIMS Forum 2018. While Ocrevus-treated patients improved their ability to read low-contrast letters over the course of the two trials, people who received Rebif (interferon beta-1a) did not. Laura J. Balcer, a neurologist at New York University Langone Medical Center, shared the data in a presentation titled, “Effect of Ocrelizumab on Visual Outcomes in Patients with Baseline Visual Impairment in the OPERA Studies in Relapsing Multiple Sclerosis.” Balcer had earlier shared data on the visual outcomes of relapsing patients in the OPERA I and OPERA II Phase 3 clinical trials of Ocrevus at the 7th Joint ECTRIMS-ACTRIMS Meeting in Paris, last year. The two studies — sponsored by Ocrevus developer Genentech, a member of the Roche group —  compared Ocrevus and Rebif in patients with relapsing MS. This time, her presentation focused only on patients who had visual impairment when they enrolled in the trials. Among a total of 1,656 participants, 375 of those treated with Ocrevus and 373 in the Rebif group had visual impairment. Researchers tested vision using a low-contrast letter acuity test. The test is similar to an ordinary vision test, with letters of different sizes on a chart. But the low-contrast test uses gray letters — instead of black — on a white background. Researchers included charts with two shades of gray to test different contrast levels. These tests can detect reduced visual function. At the beginning of the trials, both groups performed in a similar manner — correctly identifying about 35 letters on a chart with somewhat higher contrast. After 96 weeks, those receiving Ocrevus identified on average 3.4 more letters, while Rebif-treated patients worsened by 0.5 letters — a significant difference, Balcer said. Researchers tested vision every 12 weeks. At the end of the trials, they found that 39 percent more patients in the Ocrevus groups had a cumulative improvement of at least 10 letters, compared to those treated with Rebif. At this time, 26.4 percent of Ocrevus-treated patients improved 10 letters or more, compared to 19.8 percent in the Rebif group. The difference between the groups for at least seven letters was 54 percent, with Ocrevus-treated patients performing better. Researchers believe that a seven-letter change is the minimal clinically important difference for the test. Based on the results, researchers believe that the findings demonstrate Ocrevus’ ability to reverse visual impairment in relapsing MS. The ACTRIMS Forum 2018 is being held in San Diego, California, Feb. 1–3.

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