Genzyme, a Sanofi company, has announced that the Canadian province of Québec’s Institut national d’excellence en santé et services sociaux (INESSS) has recommended that the company’s multiple sclerosis (MS) drug Lemtrada (alemtuzumab) 12 mg be included on the provincial drug formulary under “Médicament d’exception” as a second-line treatment for people living with relapsing-remitting multiple sclerosis (RRMS). This announcement follows decisions by international Health Technology Assessment Agencies, such as NICE in the UK in May and PBAC in Australia in August 2014.
“We are pleased that the province of Québec is leading the way in accelerating access to treatments for Canadians living with MS,” says Yves Savoie, president and CEO of the Multiple Sclerosis Society of Canada. “This announcement highlights the importance of having more treatment choices for individuals with MS to manage their disease.”
Lemtrada was approved by Health Canada in December 2013. The approval was based on data from the Lemtrada clinical development program comparing treatment of Lemtrada to high-dose subcutaneous interferon beta-1a (Rebif), which is dosed three times per week in patients with RRMS who had active disease. Lemtrada is a recombinant humanized monoclonal antibody that is a recombinant humanized monoclonal antibody and a selective immunomodulator that targets CD52, a protein abundant on T and B cells. Treatment with alemtuzumab results in the depletion of circulating T and B cells thought to be responsible for the damaging inflammatory process in MS. Alemtuzumab has minimal impact on other immune cells. The acute anti-inflammatory effect of alemtuzumab is immediately followed by the onset of a distinctive pattern of T and B cell repopulation that continues over time, altering the immune system in a way that potentially reduces MS disease activity.
Indicated for management of adult patients with RRMS, defined by clinical factors and imaging results, who have had an inadequate response to interferon beta or other disease-modifying therapies. Lemtrada is a monotherapy delivered by intravenous infusion for management of RRMS in adults with active disease defined by clinical and imaging features, to reduce the frequency of clinical exacerbations (relapses) and to delay progression of physical disability.
According to a Multiple Sclerosis Society Of Canada (MSSoC) drug profile, clinical trial results from a study assessing the safety and efficacy of alemtuzumab compared with interferon beta 1a as a first line therapy in previously untreated people with relapsing-remitting MS, demonstrated treatment with alemtuzumab to be more effective at the end of the study period than treatment with interferon beta 1a.
Additionally, they say findings from a separate study assessing the safety and efficacy of alemtuzumab compared with interferon beta 1a in people with relapsing-remitting MS who have relapsed despite first-line treatment (interferon beta or glatiramer acetate) suggest that alemtuzumab was more effective in reducing relapse rate and disability progression compared with interferon beta 1a.
Interim results from the first year of the extension study of Lemtrada were presented March 21, 2013 at the American Academy of Neurology meeting in San Diego, California.
Lemtrada is supported by a comprehensive and extensive clinical development program that involved 1,188 patients, resulting in 2,363 patient-years of safety follow-up.
The Phase III trials of Lemtrada were randomized, two-year pivotal studies comparing treatment with Lemtrada to Rebif (subcutaneous interferon beta-1a 44 mcg) in patients with relapsing-remitting MS who were either new to treatment (CARE-MS I) or who had relapsed while on prior therapy (CARE-MS II).
The CARE-MS trials were Phase III, global, randomized clinical trials designed to evaluate whether the investigational MS therapy Lemtrada could achieve meaningful efficacy and safety improvements over the approved, active comparator Rebif (subcutaneous interferon beta-1a 44 mcg), a standard treatment for relapsing-remitting MS.
The CARE-MS I study evaluated 581 patients naïve to prior MS treatment, except for steroids. The CARE-MS II study evaluated 840 patients who have had at least one relapse occurring while on MS therapy, including standard injectable disease modifying therapies. Genzyme announced publication of results of these studies in The Lancet in November 2012.
In the both trials, Lemtrada was given as an IV administration a total of eight times over the course of the two-year study. The first treatment course was administered on five consecutive days, and the second course was administered on three consecutive days 12 months later. Rebif (interferon beta-1a) 44 mcg was administered by subcutaneous injection three times per week, each week, throughout the two years of study.
As Lemtrada patients require monitoring at regular intervals between treatment courses and for 48 months following the final infusion, Genzyme is providing every patient with a unique, comprehensive and free patient support program. The MS One to One program will offer comprehensive support services, including: counseling, pre-treatment testing, coordination of infusion appointment and location, post-treatment monitoring at the patients preferred location (lab, infusion centre or in-home), delivery of test results directly to patients healthcare provider, patient education and compliance services, as well as reimbursement navigation and other financial assistance. Staffed by dedicated MS nurses and highly trained representatives, MS One to One can provide support for individuals living with MS who are receiving Genzyme MS therapies, their health care providers, family and loved ones.
In the third-year following initial treatment, starting the extension phase of the trials, patients who experienced resumed disease activity were retreated with Lemtrada once daily for three days. Patients who took Rebif in the pivotal study phase and crossed over to receive Lemtrada in the extension phase received Lemtrada once daily for five days and then once daily for three days one year later.
Genzyme reports that more than 90 percent of patients participating in the Phase III pivotal trials enrolled in the extension study. Patients who originally received Lemtrada were eligible to receive additional treatment in the extension study if they had experienced at least one relapse or at least two new or enlarging brain or spinal lesions.
These interim results are from the first year of the extension study for patients who previously received Lemtrada in the two-year studies. Findings cited are based on patients who enrolled in the extension study:
More than half of patients (67 percent in CARE-MS I and 55 percent in CARE-MS II) who received Lemtrada in the pivotal trials and enrolled in the extension study were still relapse-free through the first year of the extension study.
In the first year of the extension phase, the annualized relapse rate for patients who received Lemtrada in the pivotal trials was 0.24 and 0.25, comparable to the annualized relapse rate for those patients in CARE MS I and CARE-MS II, respectively.
Through year three, 72.4 percent of patients in CARE MS I and 70.0 percent in CARE MS II had improved or stable disability as measured by EDSS.
At three years, 88 percent and 80 percent of patients who received Lemtrada in the pivotal trials, respectively, did not experience six-month confirmed sustained accumulation of disability.
During an extensive, ongoing clinical development program, 80 percent of RRMS patients who received two treatment courses of Lemtrada required no further therapy, and 55 percent remained relapse-free through the first year of the extension study. Unlike other current disease modifying therapies (DMTs) in which stopping treatment usually results in resumed disease activity, Lemtrada continues to have a durable effect far beyond the two annual treatment courses. In fact, in more than 70 per cent of clinical trial patients, disability scores improved or remained stable over three years.
“These results underscore the tremendous promise that Lemtrada holds for MS patients,” commented David Meeker, M.D., Genzyme’s President and Chief Executive Officer. “We’re pleased to be able to present these three-year results that provide us with important new information about Lemtrada and are consistent with the published results from our Phase II extension study.”
Genzyme says safety results from the first year of the extension study were reported for patients who received Lemtrada in the Phase III pivotal studies. No new risks were identified. The frequency and type of common and serious adverse events in the first year of the extension study were generally similar to those in the Phase III pivotal studies. The most common adverse events during this period of time were infections, including predominantly mild to moderate upper respiratory and urinary tract infections.
There were two deaths. One, as previously reported, was from sepsis. The other death was presumed accidental and deemed unrelated to study treatment. The cumulative incidence of autoimmune thyroid disease over three years was 29.9 percent, as expected based on the Phase II study experience. Additionally, over three years, approximately 1 percent of patients developed immune thrombocytopenia (ITP) and 0.3 percent developed nephropathy, all of whom responded to treatment. These cases were detected early through routine monitoring. Patient monitoring for autoimmune disorders is incorporated in all Genzyme-sponsored trials of Lemtrada.
The most common side effects of Lemtrada are infusion-associated reactions (headache, rash, pyrexia, nausea, urticaria, pruritus, insomnia, chills and flushing) and infections (nasopharyngitis, urinary tract and upper respiratory tract). Serious infections and autoimmune conditions, including thyroid disease, cytopenias, and kidney disease can occur in patients receiving Lemtrada. A comprehensive risk management program incorporating education and monitoring will support early detection and management of these identified risks.
Québec’s reimbursement criteria for Lemtrada are:
• For the monotherapy treatment of people with relapsing-remitting multiple sclerosis (RRMS),
• Diagnosed according to the McDonald criteria (2010)
• Experiencing at least two relapses in the previous 2 years, of which one must have taken place during the past year. In addition, one of them must have occurred while the patient was taking a DMT listed under RAMQ list of drugs for the treatment of this disease for at least six months under certain conditions
• EDSS must be equal to or lower than 5.
The authorization of the initial request is for a cycle of five consecutive days of treatment at a daily dose of 12 mg to cover the first year of treatment.
To continue treatment after the first year, the physician must provide evidence of a beneficial effect on annual relapse rate in addition to a stabilization of the result on the EDSS or an increase of less than 2 points without exceeding 5.
Authorization of the second request is for a cycle of 3 consecutive days of treatment at a daily dose of 12 mg given 12 months after the first cycle. Thus, the total allowed duration of treatment is 24 months.”
“The Multiple Sclerosis Society of Québec welcomes the INESSS recommendation to add Lemtrada under Médicament d’Exception to Quebec’s drug formulary. We are delighted with this news since access to treatments for people with MS is paramount,” says Louis Adam, General Manager, Multiple Sclerosis Society of Canada, Québec Division.
The INESSS recommendation is based on the Phase III study CARE MS II (Coles 2012) to evaluate the therapeutic value of Lemtrada and according to the Health Canada indication. The CARE MS II trial has shown that, as a second-line treatment, Lemtrada is more effective than interferon beta-1a in reducing the annual relapse rate and the time to onset of sustained accumulation of disability. Lemtrada with its novel mechanism of action will complement the range of therapeutic options for the patients suffering from RRMS.
“We are very pleased to learn that the transformative potential of Lemtrada will be available to all Québecers living with relapsing MS,” says Peter Brenders, CEO of Genzyme Canada. “We applaud the Québec government for its leadership in health care, as this approval underscores Lemtrada’s capability to have a positive impact on the lives of MS patients.”
As part of its commitment to those living with MS, Genzyme has developed the MS One to One program which provides comprehensive and effective support, particularly with regard to the procedures for reimbursement and administration, as well as providing educational resources. Staffed by dedicated MS nurses and highly trained representatives, MS One to One provides support for individuals living with MS, their healthcare providers, family and loved ones.
With 100,000 Canadians living with MS and three people newly diagnosed every day, Canada has one of the highest MS prevalence rates in the world. As most people are diagnosed with relapsing MS in their twenties and thirties, MS is the most common neurological disease affecting young adults in Canada.
As a debilitating disease, MS symptoms can include: blurred or loss of vision, poor coordination, slurred speech, extreme fatigue, diminished mobility of the arms or legs, problems with memory and concentration, and bladder and bowel dysfunction
As a Sanofi company, Genzyme benefits from the reach and resources of one of the world’s largest pharmaceutical companies, with a shared commitment to improving the lives of patients. Learn more at:
Multiple Sclerosis Society of Canada