Tysabri, a fifth disease modifying drug (DMT) for MS, had been approved by provinces of Quebec, Alberta and now Saskatchewan (as July 1, 2009) for reimbursement by provincial drug plans. Due to the expense of the therapy ($40 000 per year) some conditions were included by the various provincial funding plans before funding was approved. Mostly these conditions consisted of failure under 2 previous uses of currently approved drugs was required before Tysabri could be approved in these 3 provinces.
The advocacy occured with MPPs all across Ontario. In Durham Region letters were sent to all 5 Durham MPPs with this additional information and a letter (see below) to lobby Honourable David Caplan, Minister of Health and Long-Term Care, requesting that the Committee to Evaluate Drugs (CED) approve funding for reimbursement the Ontario Trillium Drug plan.
The letter included was from Yves Savoie, President Ontario Division and from Mark Freedman, Director MS Research Ottawa Hospital and internationally renowned research neurologist, requesting funding approval with no conditions be attached. The gist of the letter is neurologists should be allowed the freedom to prescribe what they feel is the best therapy for their patients. A copy of this letter is provided at the very end of this article.
Finally, approval was given by the Exceptional Access Program on September 30th for individuals whose condition worsens after 6 months while under treatment with one of the other EAP approved drugs for MS. The Ontario Drug Benefit Program will approve an initial treatment period of 6 months for patients requiring the administration of Tysabri for the treatment of Rapidly Evolving Severe Relapsing-Remitting Multiple Sclerosis (RES-RRMS) with renewal upon application by patient’s neurologist.
RES-RRMS means 2 or more disabling relapses with incomplete recovery in previous year, failure to improve with one other DMT (like Copaxone or Rebif) over a period of 6 months and MRIs showing lesions on the brain or increasing number lesions on brain compared to a previous MRI.
The following is from a letter dated December 16, 2009 from Deb Matthews, Minister of Health and Long Term Care giving more detail about its approval process for Tysabri:
In response] to your letter to the Honourable David Caplan, former Minister of Health and Long-Term Care, regarding coverage of the drug Tysabri used in the treatment of Multiple Sclerosis.
I am pleased to tell you that Tysabri may be considered for funding under the Exceptional Access Program (EAP) according to specific criteria for the treatment of Multiple Sclerosis.
As you may know, Ontario has an established process for reviewing requests for drug funding under the public drug program. For manufacturer initiated submissions, the ministry's expert advisory committee, the Committee to Evaluate Drugs (CED), reviews and considers the drug's clinical value and conducts a thorough assessment of the scientific and clinical evidence contained in the manufacturer's submission, as well as the impact on health services compared to existing treatments. The CED then makes a recommendation to the Executive Officer on whether or not the drug should be listed in the Ontario Drug Benefit Formulary or considered for funding on a case-by-case basis through the EAP. The Executive Officer will make the final decision as to whether a drug should be funded based on the CED's recommendation, the overall budget and public interest.
In March and May 2009, the CED reviewed a submission from the manufacturer of Tysabri. The CED reviewed the clinical evidence contained in the submission and noted that Tysabri appears to have an effect in the treatment of Rapidly Evolving Severe Relapsing-Remitting Multiple Sclerosis (RES-RRMS). The CED also recognized that RES-RRMS is a very debilitating disease where there is limited alternative therapy available. However, the CED was concerned with the true cost-effectiveness of funding Tysabri as there were many limitations to the economic analysis provided in the submission. As a result, the CED recommended that Tysabri be considered for funding on a case-by-case basis through the EAP for Multiple Sclerosis.
For your information, as part of the background for this article, the following is the letter sent as part last summer’s advocacy by Social Action Directors from Yves Savoie, President, Ontario Division, and Mark Freedman, Director MS Research Clinic Ottawa Hospital
As well two very clinical papers supporting this proposal were sent as well but are not included here due their length and technical nature.
April 23, 2009
Ms. Helen Stevenson
Assistant Deputy Minister & Executive Officer
Ontario Public Drug Programs Division Hepburn Block, 9th Flr. 80 Grosvenor St Toronto ON M7A1R3
Dear Ms. Stevenson:
We are writing on behalf of the Multiple Sclerosis Society of Canada, Ontario Division. We are writing on behalf of the Multiple Sclerosis Society of Canada, Ontario Division. We are aware that you and your officials are considering the inclusion of natalizumab (Tysabri) for reimbursement by the Ontario Drug Benefit Program.
The MS Society is very pleased this review is underway. We believe that this new therapy should be available to people with MS who may benefit from it as soon as possible. As you are aware, Health Canada approved Tysabri in September 2006. In February 2009, the Canadian Expert Advisory Committee of the Common Drug Review recommended that publicly funded drug programs add Tysabri to their formularies, under certain criteria.
The MS Society welcomes the CDR recommendation. However, we would like to point out that the treatment of MS is highly individualized, and people with MS and their physicians need to have the widest choice possible to manage this often disabling disease. We note the CDR recommendation requires, among other criteria, that people not qualify for reimbursement of Tysabri until they have failed on treatment with two other disease-modifying therapies.
The definition of “failure” has been a difficult one, prompting Canadian neurologists to adopt a different definition of “sub-optimal” response to therapy (please see the attached papers published in the Canadian Journal of Neurosciences, 2004; 31: 157-168 and 2008;35: 127-129). In the CDR recommendation, failure is based on two criteria. The first is the appearance of “disabling” relapses; however, “disabling” is never defined. Second, failure is described as the appearance of new MRI activity. This is problematic given that adequate access to MRI scanning is an ongoing issue in Ontario. This approach to “failure” within the CDR recommendation defeats, to a large extent, the otherwise cautious and responsible recommendations of the CDR.
Leading MS neurologists generally agree that early intervention with effective therapy to control the disease poses the best chance for long term benefit. Delaying access to effective therapy could result in potentially avoidable disease progression and disability. Most MS neurologists consider there to be a “window of optimal anti-inflammatory based therapy” based on time, and once people with MS advance beyond the window, such treatments become less effective. There is little evidence that a person otherwise tolerating a first line disease-modifying therapy (i.e. interferon-beta or glatiramer acetate) who experiences a significant “sub-optimal” response will respond to a different first line therapy. The concern is that these people with MS might be advancing quickly out of their “window”, and the best treatment might very well be a course of therapy with natalizumab.
Currently the alternative, escalating treatment for people with MS who are no longer responding to interferon-beta or glatiramer acetate, is chemotherapy such as mitoxantrone. Delaying this “escalation” by requiring another 6-12 month treatment period with another first line agent could easily put people with MS into a situation where the escalation therapy, when it is finally used, is ineffective at staving off disease progression.
Additionally, as mentioned, there is inadequate access to MRI, particularly with gadolinium enhancement, in many parts of the province of Ontario. Thus, requiring access to ascertain the status of MRI activity in patients may add yet more delay. We feel that putting natalizumab in the hands of our experienced neurologists to be used as an important treatment option is imperative. The MS Society is also cognizant of the worries concerning the long term treatment with natalizumab. Nevertheless, until new recommendations regarding its safety are available, we do not feel that this should further delay the availability of natalizumab for all of our patients.
The MS Society therefore urges you to move quickly to include Tysabri among the MS therapies that are reimbursed, and that criteria for reimbursement be developed based on input from our expert MS neurologists. Specifically, we urge that expert advice be sought on the CDR recommendations based on “failure” so that patients who experience a sub-optimal response to first line therapy have available to them natalizumab for use at a time when it is apt to have its maximal benefit.
In addition, we urge the criteria include people who are currently doing well on Tysabri and have to move from an employer-paid extended benefits plan to the publicly-funded drug program because of reasons outside of their control. This would ensure that these individuals need not discontinue treatment due to financial circumstances.
In a clinical trial of two years' duration, (the AFFIRM study), 942 individuals received either Tysabri or inactive placebo. The treated group experienced a 42 percent reduced risk of progression of disability, a 68 percent reduction of clinical relapses, and an 83 percent reduction in the development of new or newly enlarging MRI-detected brain lesions. Tysabri also reduced the mean number of enhancing (active) MRI lesions by 92 percent after the first and second year. These results were published in The New England Journal of Medicine 2006;354:899-910.
In addition, it is important to note to date, all countries in Western Europe, many in Eastern Europe, Australia and the United States (through Medicare and Medicaid) have agreed that Tysabri should be reimbursed as an appropriate treatment for multiple sclerosis. Quebec has also agreed to reimburse the cost of Tysabri under certain criteria.
In a country with one of the highest rates of MS in the world and internationally recognized and experienced MS clinicians leading the way in MS research it is imperative that physicians have in their hands all the options necessary to optimally treat people with MS and that includes the choice of therapy and access to proper imaging. All provinces, including Ontario, should strive to make these options available to people with MS.
A representative of the MS Society will follow up with you to schedule a meeting at your earliest convenience.
Yves Savoie Mark Freedman, MD, FRCP(C)
President and Chief Executive Officer Director, MS Research Clinic
President, Ontario Division Ottawa Hospital
Cc Paul O’Connor, MD, Scientific & Clinical Advisor, Multiple Sclerosis Society of Canada
Enc. The Use of Disease-Modifying Agents in Multiple Sclerosis
Treatment Optimization in Multiple Sclerosis