Author Topic: Lemtrada (alemtuzumab) to be available on the NHS for active RRMS  (Read 210 times)

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Offline agate

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Lemtrada, which the US FDA rejected, has been approved for the NHS in the UK. Below is an excerpt of an article in Medical News Today, May 29, 2014:

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NICE recommends Lemtrada® (alemtuzumab) for use on the NHS for the treatment of active relapsing remitting multiple sclerosis


The National Institute for Health and Care Excellence (NICE) has issued final guidance recommending that Lemtrada should be reimbursed on the NHS, as an option for treating adults with active RRMS, within its marketing authorisation. Lemtrada has been shown to significantly reduce annualised relapse rates in both treatment-naïve and treatment-experienced adult patients with active RRMS versus an active comparator. [ii],[iii]

Lemtrada, a humanised monoclonal antibody therapy, is the first MS therapy to demonstrate superior reduction in the risk of disability accumulation in treatment-experienced people, when compared to subcutaneous interferon beta 1a (SC IFNB-1a).3 "We are delighted that after many years in development, Lemtrada is now available on the NHS. Treatments which have the potential to improve the lives of those living with MS should be available to all who might benefit. Lemtrada offers an important additional treatment option which will be welcomed by the MS community," said Amy Bowen, Director of Service Development at the MS Trust. Unlike other MS treatments currently available, Lemtrada is administered in two short treatment courses, one year apart.[iv]

Lemtrada is the second of Genzyme's treatments for MS to receive approval for use from NICE and become available on the NHS.1 Lemtrada has been in clinical development for MS for more than 10 years and the development programme involved more than 1,500 patients.

...

Approximately 100,000 people in the UK have MS and about 2,500 people are newly diagnosed with it each year.[v] Eighty-five percent of people with MS are initially diagnosed with RRMS, and people with RRMS experience approximately one or two relapses per year.[vi], [vii] Around half of all relapses may leave people with lingering problems, and symptoms may worsen over time.

About Lemtrada (alemtuzumab)

Lemtrada is a humanised monoclonal antibody therapy which selectively 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 transient impact on other immune cells. The reduction in the level of circulating T and B cells by alemtuzumab and subsequent repopulation may reduce the potential for relapse, which ultimately delays disease progression. Patients treated with Lemtrada had fewer relapses compared to patients treated with a beta-interferon injected multiple times per week, and treatment experienced patients were less likely to experience worsening of their disability. Lemtrada is administered in two short treatment courses.

The first treatment course includes one infusion per day for five days (course one). A year later a second course is administered one infusion per day for three days (course two). Lemtrada had been in clinical development for MS for more than 10 years and is supported by an extensive multicentre, multi-country clinical programme. Lemtrada was developed as part of research at the University of Cambridge and more than 1,500 patients received Lemtrada treatment course as part of these clinical trials.

EU Indication and Usage

Lemtrada is indicated in the European Union for the treatment of adult patients with relapsing remitting multiple sclerosis with active disease defined by clinical or imaging features.[viii] Genzyme have introduced a risk management plan to ensure that Lemtrada is used as safely as possible. Based on this plan, safety information has been included in the Summary of Product Characteristics (SmPC) and the Patient Information Leaflet for Lemtrada, including the appropriate precautions to be followed by healthcare professionals and patients.

For full prescribing information about Lemtrada, the Summary of Product Characteristics can be found here, which includes the data that has supported the license indication: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/003718/WC500150521.pdf



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References

National Institute for Health and Care Excellence. Final appraisal determination (FAD). Alemtuzumab for treating relapsing–remitting multiple sclerosis. March 2014

[ii] Cohen et al. Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a RCT phase III trial. The Lancet 2012; 380: 1069-1078

[iii] Coles et al. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a RCT phase III trial. The Lancet 2012; 380: 1829-1839

[iv] Genzyme. Alemtuzumab Summary of Product Characteristics (SmPC) December 2013

[v] NICE Proposed Health Technology Appraisal. Alemtuzumab, dimethyl fumarate, laquinimod and teriflunomide for the treatment of relapsing forms of multiple sclerosis. Draft scope. http://www.nice.org.uk/nicemedia/live/14061/63485/63485.pdf [Accessed October 2013]

[vi] MS Society. Relapsing Remitting (RRMS). http://www.mssociety.org.uk/what-is-ms/types-of-ms/relapsing-remitting-rrms [Accessed May 2014]

[vii] Multiple Sclerosis Trust. Types of MS. http://www.mstrust.org.uk/atoz/types.jsp [Accessed May 2014]

[viii] EPAR Summary for the public. Lemtrada (alemtuzumab) European Medicines Agency. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Summary_for_the_public/human/003718/WC500150523.pdf [Last accessed May 2014]




The entire article is available here.
MS Speaks--online for 17 years

SPMS, diagnosed 1980. Avonex 2001-2004. Copaxone 2007-2010. Glatopa (glatiramer acetate 40mg 3 times/week) since 12/16/20.

Offline agate

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Lemtrada now approved in Scotland
« Reply #1 on: July 21, 2014, 08:32:05 am »
Excerpted from MS Weekly News (BioNews Services), July 21, 2014:

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Lemtrada For RRMS Still Under Revision in the U.S., Now Approved in Scotland

 Leonor Mateus Ferreira

The Scottish Medicines Consortium (SMC)  announced the approval of the drug Lemtrada, produced by Genzyme, for the treatment of adult patients with relapsing-remitting multiple sclerosis (RRMS) and active disease defined by clinical or imaging features, within the national health system (NHS) in Scotland.

Lemtrada (alemtuzumab), a humanised monoclonal antibody therapy, has been proven effective in the depletion of circulating T and B cells, which are responsible for the damaging inflammatory process in MS. Reducing the levels of circulation of T and B cells using the medication is believed to reduce the potential for relapse, as well as the disease progression.

“Scotland has one of the highest rates of multiple sclerosis in the world, and the approval of Lemtrada in Scotland is an important step forward for people with active RRMS who remain in need of new treatment options,” said Dr. Belinda Weller, Consultant Neurologist, Western General Hospital, Edinburgh. ”MS treatments have come a long way in the past twenty years and the availability of Lemtrada provides an opportunity for neurologists to offer a new therapy to people with multiple sclerosis.”

Throughout the course of numerous clinical trials conducted over the past ten years, Genzyme has verified that patients treated with Lemtrada reduced annualized relapse rates compared to patients treated with subcutaneous beta-interferon injected three times per week. Patients also revealed less possibilities of experiencing disability. As a result of research developed in collaboration with the University of Cambridge, more than 1,500 patients were administrated the drug in two short treatment courses. The first course included one infusion per day for five days and, one year later, the second course included one infusion per day for three days.

“RRMS accounts for eighty-five percent of all initial diagnoses in MS. We are pleased that after many years in development, Lemtrada is now available to patients in Scotland. This provides people with MS with an important and innovative treatment option to consider in partnership with their MS specialists,“ said Amy Bowen, Director of Service Development at the MS Trust.

This is second therapy from Genzyme to receive approval from the SMC and to be made available in Scotland. The drug has already been approved for NHS patients both in England and Wales, after having been approved by the National Institute for Health and Care Excellence (NICE).

...


The drug, which is still under review in the United States, was recently approved in Argentina as well, by the National Administration of Drugs, Food and Medical Techology (ANMAT).

MS Speaks--online for 17 years

SPMS, diagnosed 1980. Avonex 2001-2004. Copaxone 2007-2010. Glatopa (glatiramer acetate 40mg 3 times/week) since 12/16/20.

Offline agate

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Alemtuzumab for RRMS (Lancet)
« Reply #2 on: August 19, 2014, 02:31:46 pm »
From Lancet Neurology, August 19, 2014:

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Alemtuzumab for relapsing-remitting multiple sclerosis

Richard A Diaz a, Sally Doss a, Martyn J Burke a, Elisabeth George a, Amanda I Adler a

On May 28, 2014, the UK National Institute of Health and Care Excellence (NICE) published guidance recommending alemtuzumab as an option, within its licence, for the treatment of relapsing-remitting multiple sclerosis (RRMS).

Alemtuzumab, a monoclonal antibody directed against lymphocytes, was appraised under the Single Technology Appraisal process. The appraisal's remit was to assess the clinical and cost effectiveness of alemtuzumab, within its licensed indication, for the treatment of RRMS. Genzyme, who manufacture alemtuzumab under the brand name Lemtrada, submitted clinical evidence and a health economic model that was critiqued by an independent Evidence Review Group from the University of Southampton. A NICE Appraisal Committee met twice on Oct 22, 2013, and Feb 18, 2014, to consider the evidence, to hear from clinical specialists, patient experts, and Genzyme, and to develop the guidance.

The key clinical evidence for the appraisal included results from three randomised, controlled clinical trials that compared intravenous alemtuzumab with subcutaneous interferon beta-1a (brand name Rebif): CARE-MS I (n=581), CARE-MS II (n=1046), and CAMMS223 (n=334). The evidence also included results from an extension study: CAMMS03409 (n=1322, median follow-up of 7·1 years), which enrolled people from the above-listed trials. In CAMMS223, patients from CARE-MS I and CARE-MS II were randomly given either subcutaneous interferon beta-1a 44 μg three times per week or intravenous alemtuzumab 12 mg once per day for 5 days, followed 12 months later by a 3-day course. Some participants were given alemtuzumab beyond two courses.

Alemtuzumab compared with interferon beta-1a significantly reduced the risk of disability lasting for at least 6 months, the trials’ co-primary outcome, in CARE-MS II by 42% and in CAMMS223 by 75%. In CARE-MS I, the risk of disability lasting for 6 months or longer was lower with alemtuzumab compared with interferon beta-1a, but the difference was not statistically significant. Alemtuzumab significantly reduced the relapse rate compared with interferon beta-1a by 55% in CARE-MS I, by 49% in CARE-MS II, and by 69% in CAMMS223. On the basis of these studies, the Committee concluded that alemtuzumab was more effective in the short term than interferon beta-1a for the treatment of RRMS, but that its long-term effectiveness was uncertain.

Alemtuzumab permanently changes the immune system and is associated with some severe adverse effects, notably autoimmune thyroid-related disease, nephropathy, and idiopathic thrombocytopenic purpura.

The Committee concluded that some people with RRMS (even with moderate disease) might accept the disadvantages of alemtuzumab, that clinicians should monitor patients, and that Genzyme should accurately document the risks, including any deaths that had occurred during the trials. The committee considered the European Public Assessment report, which includes a discussion about clinical safety presented by the manufacturer to the European Medicines Agency.

To compare alemtuzumab with current disease-modifying treatments for RRMS other than interferon beta-1a, Genzyme presented a mixed-treatment comparison including trials of alemtuzumab, subcutaneous interferon beta-1a, intramuscular interferon beta-1a, interferon beta-1b (brand name Betaferon), glatiramer acetate, natalizumab, and fingolimod. Compared with the interferons, treatment with alemtuzumab resulted in a significantly lower risk of disability. Compared with glatiramer acetate, alemtuzumab lowered the risk of disability, but the difference was not statistically significant. Genzyme focused on disability lasting for 3 months in its mixed-treatment comparison, whereas the Committee heard from clinical specialists that the outcome of disability lasting for at least 6 months is more appropriate and specific. The Committee also heard that Genzyme had excluded trials undertaken before 2000.

To address the effectiveness of alemtuzumab in two subgroups of patients, those with rapidly evolving severe RRMS and those with highly active-RRMS despite interferon beta treatment, Genzyme did two indirect comparisons. For patients with highly active-RRMS, the results showed a lower risk of disability lasting for 3 months with alemtuzumab compared with fingolimod, but the difference was not statistically significant. 6 month data were not available for fingolimod. For patients with rapidly evolving severe-RRMS, the risk of disability lasting for 6 months was lower with alemtuzumab compared with natalizumab, but again the difference was not statistically significant. While acknowledging the uncertainty of these results, the Committee concluded that alemtuzumab was at least as effective as fingolimod and natalizumab for these subgroups.

To determine whether alemtuzumab for RRMS represents a cost-effective use of UK National Health Service (NHS) resources, Genzyme estimated the cost per quality-adjusted life year (QALY) gained for alemtuzumab compared with other disease-modifying therapies. The economic model incorporated ambulatory patients and defined disability using the Expanded Disability Status Scale (EDSS) and included progression to secondary progressive MS. In the model, effective therapies slowed disease progression, but the model did not include the possibility that an individual's EDSS score could improve and therefore might not show the true course of disease. Genzyme assumed that the effectiveness of alemtuzumab did not wane over time, which was deemed implausible by the Committee. The analyses used an NHS and personal social services perspective, and a 3·5% discount rate for costs and health effects.

Genzyme's estimates of the incremental cost-effectiveness ratios (ICERs) showed that alemtuzumab was more effective at a lower cost compared with interferon beta-1b, fingolimod, and natalizumab, and that a combination of other treatments were more effective and cost less than interferon beta-1a 44 μg and 22 μg. The probabilistic ICER for alemtuzumab compared with glatiramer acetate was £7017 per QALY gained, whereas the deterministic ICER was similar at £8924. Through the use of indirect comparisons as an estimate of relative effectiveness of alemtuzumab in patients with highly active-RRMS despite interferon beta treatment or rapidly evolving severe-RRMS, alemtuzumab was more effective at a lower cost than fingolimod or natalizumab, respectively.

To test whether the results of the cost-effectiveness analyses were robust, Genzyme undertook one-way sensitivity analyses. These analyses showed that the cost effectiveness of alemtuzumab was most sensitive to how well alemtuzumab slows disease progression, disease costs, and how frequently patients discontinued subcutaneous interferon beta-1a 44 μg. According to Genzyme, alemtuzumab dominated over all comparators except glatiramer acetate, unless the manufacturer varied its assumptions around effectiveness.

During its first meeting, the NICE Appraisal Committee identified several issues and uncertainties with Genzyme's submission. The Committee agreed that alemtuzumab was not a cost-effective use of NHS resources on the basis of the evidence presented at that stage and asked Genzyme to provide further evidence and analyses. Among other requests, it asked the manufacturer to: incorporate a more realistic natural history of disease; adjust relapse rates; include trials before the year 2000 in its mixed-treatment comparison; include details of within-trial deaths; incorporate a waning of effectiveness of alemtuzumab over time in its analyses; model retreatment with alemtuzumab over time; and use utility values, which are based on health-related quality of life values collected before, during, and after clinical studies and can be incorporated into cost-effectiveness analyses, that were collected within the alemtuzumab trials.

At its second meeting, the Committee considered responses to its preliminary guidance from consultees, commentators, and the general public, and the additional evidence and economic analyses from Genzyme. The Committee considered Genzyme's revised case, which combined each of the Committee's preferred assumptions and included several scenarios (eg, incorporating a 3-year or 5-year waning effect into the model). The Committee concluded that the most plausible ICER for alemtuzumab compared with glatiramer acetate for people with active RRMS was probably between £13 600 and £24 500 per QALY gained, and depended on assumptions about the waning of treatment effect. For patients with active RMSS for whom current treatment included either an interferon or glatiramer acetate, the Committee concluded that alemtuzumab could be considered cost-effective.
The Committee reviewed the revised analyses from Genzyme for patients with highly active RRMS despite interferon treatment or with rapidly evolving severe RRMS. When the manufacturer combined the Committee's preferred assumptions and an estimate of the cost effectiveness of alemtuzumab relative to the comparators, alemtuzumab was better than each comparator. The previous analyses from Genzyme had concluded that within these disease subgroups alemtuzumab was at least as effective as fingolimod and natalizumab; for the new analysis, assuming equal efficacy in the economic model, the most plausible ICER for patients with highly active RRMS despite interferon beta treatment was £8900 per QALY gained for alemtuzumab compared with fingolimod. Additionally, the analysis showed that alemtuzumab was better than natalizumab for patients with rapidly evolving severe-RRMS.

The Committee concluded that alemtuzumab could be considered a cost-effective treatment for both disease subgroups and an effective use of NHS resources. The Committee recommended alemtuzumab as an option, within its licence, for treatment of RRMS. NICE received no appeals against the guidance.

We declare no competing interests.

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a National Institute for Health and Care Excellence, City Tower, Piccadilly Plaza, Manchester, M1 4BT, UK

The article can be seen here.
MS Speaks--online for 17 years

SPMS, diagnosed 1980. Avonex 2001-2004. Copaxone 2007-2010. Glatopa (glatiramer acetate 40mg 3 times/week) since 12/16/20.