Longer-term data indicate the effects of Lemtrada are long-lasting in patients with relapsing-remitting multiple sclerosis (RRMS).
An extension study showed patients treated with the drug remained free of new MRI disease activity for up to four years, even though most of them had not had a treatment for 3 years.
The rate of brain atrophy also remained low in these patients at the end of four years.
The drug, which targets the CD52 antigen found in abundance on B cells and T cells, received US Food and Drug Administration approval in November to treat patients with MS in whom two other therapies had failed. The drug depletes these B and T cells, which are thought to cause the damaging inflammatory process in MS, before these cells "come back and repopulate," said MS expert Ann Bass, MD, Neurology Center of San Antonio, Texas.
It's believed this distinctive pattern of B and T cell repopulation may rebalance the immune system.
But the drug carries risks for significant adverse effects, which can include infusion-associated reactions such as itchiness, gastrointestinal adverse effects, kidney disease, infections, and thyroid disorders, that require "heavy" laboratory monitoring, said Dr Bass.
For this reason, Lemtrada is typically used only in patients with highly active disease. "Candidates for this treatment include those who have already had a relapse on their current therapy, those who have MRI activity that's breaking through on the current therapy, and those who have disability progression that's worsening even on current therapy," said Dr Bass.
The two-year multicenter, rater-blinded study, CARE-MS II, one of two pivotal trials for the drug, showed that compared with patients with RRMS taking subcutaneous interferon β-1a, 44 μg, those who had received a baseline Lemtrada treatment (12 mg) and another treatment at 12 months had a 49 per cent decreased annualised relapse rate and a 42 per cent decrease in six-month sustained accumulation of disability.
The drug seems to have "this nice control of the disease in the absence of ongoing treatment, which is quite novel," commented Anthony Traboulsee, MD, University of British Columbia, Canada.
"One of the important questions is how long will this last before there is some breakthrough disease activity."
That, he said, was the point of the open-label extension study.
At the end of the original two-year trial, patients who were receiving interferon could opt to begin taking the drug, and those who were already taking it could receive additional treatments — a third and fourth cycle — as needed.
For this analysis, MRI outcomes included gadolinium (Gd)-enhancing, new or enlarging T2 hyperintense and new T1 hypointense lesion activity; freedom from MRI activity (absence of Gd-enhancing and new or enlarging T2 lesions); and brain volume loss measured by change in brain parenchymal fraction (BPF).
Of the original study cohort, 393 (92.9 per cent) patients entered the extension phase. At four years, 67.7 per cent of these patients had received only the initial two courses of treatment, 24.2 per cent had needed one additional course, and 7.4 per cent had received two additional courses.
The proportions of patients free of Gd-enhancing lesions were 86.5 per cent and 89.1 per cent at years three and four respectively. The numbers of new or enlarging T2 (69.0 per cent and 70.3 per cent) or new T1 lesions (87.5 per cent and 86.3 per cent) remained stable.
Most patients were free of MRI activity at year three (68.4 per cent) and year four (69.9 per cent).
"What makes it novel is the fact you can go for years and years after your treatment without having new MRI activity," commented Dr Traboulsee.
The durable effects of the drug may be due to the distinct pattern of lymphocyte depletion and repopulation following treatment, said Dr Traboulsee.
Source: Medsape Multispeciality © 1994-2015 by WebMD LLC (04/06/15)
Speaking at the 2015 Annual Meeting of the Consortium of Multiple Sclerosis Centers in Indianapolis, Indiana, Mr Samuel F. Hunter, MD, PhD, president of the Advanced Neurosciences Institute in Franklin, Tennessee, gave a presentation on outcomes in patients with relapsing multiple sclerosis (MS) treated with Lemtrada (alemtuzumab).
He said the first trial began 24 years ago, so primary care physicians may want to share this with their MS patients who are concerned about trying a “new” drug.
Hunter said Lemtrada is thought of as a “permanent” disease-modifying therapy.
“It cleans the immune system up, both the B and T cells. Transiently, it removes a lot of these cells and lets the immune system reconstitute. No one knows how it can make MS better yet, but the immune system is different,” he said.
At the same time, there is a risk of autoimmunity, infusion reactions, and malignancies, including thyroid cancer, melanoma, and lymphoproliferative disorders in patients who receive treatment.
He said Lemtrada was the first drug that was tested head-to-head with interferon beta-1a, which is the standard treatment. In the two trials that were done, he said it was clear Lemtrada was much more effective than interferon beta-1a.
“The longer it goes, the better it looks because you’re changing the immune system with Lemtrada,” he said.
Hunter added that Lemtrada is good in the short term and even better in the long term for relapsing-remitting MS.
“This is a big stick for treating relapsing MS,” he said. “It has a little more risk than other treatments, but you get something for it that any internist could manage.”
This includes monthly laboratory testing for kidney problems at the manufacturer’s expense to watch for blood, thyroid, or kidney problems.
Hunter conducted a phase I non-randomised open label study of 60 patients, using them as their own control. Most patients who switched to Lemtrada had been on the injectable drugs interferon beta-1a or Copaxone.
He said most patients stayed stable for up to two years after one treatment and then got even better with more treatments. “It’s clear Lemtrada works for a while, then it wears off and then we retreat those patients,” he said.
“MRI is really boring after treatment because it stays calm,” Hunter added. “At the same time, some will also get worse. You just have to find the treatment responders.”
Source: MD All Specialities Copyright MD Magazine 2006-2015 Intellisphere, LLC (01/06/15)
Genzyme has announced new magnetic resonance imaging (MRI) data from the Lemtrada clinical development program.
In relapsing remitting multiple sclerosis (RRMS) patients treated with Lemtrada in the Phase III pivotal studies, MRI effects observed in the two-year trials were maintained through two additional years in the extension study (years three and four). After the initial two courses of treatment in the pivotal studies, which were given at month zero and at month 12, approximately 70 percent of Lemtrada patients did not receive additional Lemtrada treatment during the following three years, through month 48.
The Phase III trials of Lemtrada were randomized, two-year pivotal studies comparing treatment with Lemtrada to high-dose subcutaneous interferon beta-1a (Rebif) in patients with RRMS who had active disease and were either new to treatment (CARE-MS I) or who had an inadequate response to another therapy (CARE-MS II).
Through year four, the adverse event profile of Lemtrada was consistent with that observed during the pivotal studies. The new data includes:
The rate of brain atrophy, as measured by brain parenchymal fraction (BPF), decreased progressively over four years among Lemtrada patients in CARE-MS I. Among CARE-MS II Lemtrada patients, the rate of brain atrophy decreased progressively over three years and remained low in year four. In both studies, the median yearly brain volume loss was less than -0.20% in years three and four, which was lower than what was observed during the two-year pivotal studies.
In CARE-MS I and II, treatment with Lemtrada significantly reduced the risk of developing new lesions compared to interferon beta-1a. In the extension study, most of the Lemtrada-treated patients from CARE-MS I and II were free of new lesions and MRI activity in years three and four (approximately 70%).
Brain atrophy is a measure of the most destructive pathological processes that occur in MS.1 It is seen from the earliest stages of disease and may lead to irreversible neurological and cognitive impairment. Given its association with disability, control or prevention of brain atrophy is an important target for MS treatment. In addition, MRI measures including lesion activity are considered useful tools when evaluating the effect of MS therapies, and lesion activity is among several prognostic factors for unfavorable clinical outcomes.
“It is very promising that most Lemtrada patients experienced slowing of brain atrophy and remained free of new lesions despite receiving their last treatment course three years previously,” said Dr. Alasdair Coles, Professor, Department of Clinical Neurosciences, University of Cambridge. “These new MRI data are consistent with the clinical data from the extension study that provide additional evidence of the sustained efficacy of Lemtrada on both relapses and disability.”
Safety results from the second year of the extension study were previously reported. No new risks were identified. The most common side effects of Lemtrada are rash, headache, pyrexia, nasopharyngitis, nausea, urinary tract infection, fatigue, insomnia, upper respiratory tract infection, herpes viral infection, urticaria, pruritus, thyroid gland disorders, fungal infection, arthralgia, pain in extremity, back pain, diarrhea, sinusitis, oropharyngeal pain, paresthesia, dizziness, abdominal pain, flushing, and vomiting. Other serious side effects associated with Lemtrada include autoimmune thyroid disease, autoimmune cytopenias, infections and pneumonitis. A risk management program incorporating education and monitoring helps support early detection and management of these identified risks.
“The four-year MRI data support the prolonged efficacy of Lemtrada,” said Genzyme President and CEO, David Meeker, M.D. “These results are encouraging, as they provide further evidence of Lemtrada’s potential to change the treatment approach for people living with relapsing forms of MS.”
More than 90 percent of the patients who were treated with Lemtrada in the CARE-MS Phase III trials enrolled in the extension study. These patients were eligible to receive additional treatment with Lemtrada in the extension study if they experienced at least one relapse or at least two new or enlarging brain or spinal cord lesions. MRI scans were taken at CARE-MS baseline, and at 12, 24, 36 and 48 months.
In CARE-MS I, Lemtrada was significantly more effective than interferon beta-1a at reducing annualized relapse rates; the difference observed in slowing disability progression did not reach statistical significance. In CARE-MS II, Lemtrada was significantly more effective than interferon beta-1a at reducing annualized relapse rates, and accumulation of disability was significantly slowed in patients given Lemtrada vs. interferon beta-1a.
Source: Market Watch Copyright ©2015 MarketWatch, Inc (24/04/15)
The U.S. Food and Drug Administration has approved Sanofi's multiple sclerosis treatment Lemtrada, Sanofi said in a statement on Saturday.
Lemtrada is already sold in Europe but last December U.S. regulators rejected it on security concerns, prompting analysts to slash their global sales forecasts for the drug.
Sanofi said in its statement that "because of its safety profile" the use of Lemtrada should generally be reserved for patients who have had an inadequate response to two or more drugs indicated for the treatment of MS.
Lemtrada is given in two courses via an intravenous drip for five days and for three days one year later.
It is designed to re-program the immune system, but in doing so can make the body more vulnerable to other diseases. FDA staff had last year flagged risks of autoimmune diseases including blood disorders, infections and cancer.
Lemtrada was at the core of Sanofi's $20 billion 2011 takeover of U.S. biotech Genzyme, which developed the drug.
Sanofi's chief executive at the time, Chris Viehbacher, who was sacked by Sanofi's board last month, had championed the move into rare diseases as he sought new areas of growth to offset the impact of patent losses on big-selling drugs.
Multiple sclerosis is a chronic, autoimmune condition which affects more than 2 million people worldwide and up to 500,000 in the United States. It attacks the central nervous system and can cause muscle weakness, pain and cognitive difficulties.
The multiple sclerosis market is increasingly moving away from injectable treatments in favour of pills such as Novartis' Gilenya and Biogen Idec's Tecfidera.
But Genzyme hopes Lemtrada's ability to reduce the risk of relapse of the disease will win it market share.
Industry observers however expect it will be reserved for patients for whom other treatments are ineffective. Analysts on average expect the drug to generate sales of just $141 million next year and just under $400 million by 2018, according to Thomson Reuters Cortellis data.
Germany's Bayer has an option to co-promote Lemtrada in the United States.
Source: Rueters © Thomson Reuters 2014 (17/11/14)
Genzyme's plans to grow its multiple sclerosis business in Europe continued with the launch of two new treatments in the Republic of Ireland.
The company, which serves as the biotech arm of French pharma firm Sanofi, today launched the injectable Lemtrada (alemtuzumab) in the country just weeks after oral multiple sclerosis (MS) treatment Aubagio (teriflunomide) hit the market.
Lemtrada will be made available to adults with active relapsing-remitting multiple sclerosis (RRMS), in accordance with its approval from the EC. It is to be given as an intravenous infusion in two annual treatment courses.
Aubagio is also available for adults with active RRMS, although it is one of several new MS treatments that come in an oral formulation, offering greater convenience to patients. It is to be taken once daily.
According to Genzyme, there are 8,000 people in Ireland with MS and around 85% will be affected by RRMS.
The launch of Lemtrada follows a recommendation in July this year from the National Centre for Pharmacoeconomics (NCPE), which provides guidance on what drugs should be reimbursed on Ireland's healthcare system to the Health Service Executive (HSE).
By contrast, Aubagio was turned down by the NCPE in June with after its assessment found that the drugs cost was not justified by its benefits.
However, in a conversation with PMLiVE, Henry Featherstone, director of public affairs at Genzyme UK & Ireland confirmed that Genzyme has since held discussions with the HSE and they have agreed that the drug can be reimbursed in Ireland.
As for where the drugs fit on the MS treatment pathway, Featherstone said that the broad indications for both products allowed doctors to discuss suitable options with patients. Further down the line, however, it's possible that Aubagio will be better suited as a first-line treatment for people with MS, while Lemtrada will be reserved for more aggressive forms of the disease.
"We hope to have these treatments available to as many people with MS as possible," Featherstone told PMLiVE. "We passionately believe in these products."
Backing Featherstone's belief, both drugs are making headway in western Europe where Lemtrada had revenues of €10m for the first six months of the year and Aubagio had revenues of €38m.
It's a different story for Lemtrada in the US, however, as the drug was turned down by the FDA at the start of 2014, much to the shock of Genzyme and Sanofi.
The decision, which was based on concerns over the drug's safety, drew criticism from the healthcare community and dozens of US doctors added their name to an open letter to the FDA to appeal the negative guidance.
Source: PMLive © PMGroup Worldwide Ltd 2014 (03/09/14)