Doubling the Dose of Glatiramer Acetate Does Not Increase Efficacy
`
`Page 1 of 2
`
`MULTISPECIALTY
`
`Medscape Conference Coverage, based on selected sessions at the:
`World Congress on Treatment and Research in Multiple Sclerosis: 2008 Joint Meeting of the American,
`European, and Latin America Committees on Treatment and Research in Multiple Sclerosis (ACTRIMS,
`ECTRIMS, LACTRIMS)
`This activity is not sanctioned by, nor a part of, ACTRIMS, ECTRIMS, or LACTRIMS. Conference news does not receive grant support
`and is produced independently.
`
`Medscape Medical News
`Doubling the Dose of Glatiramer Acetate Does Not
`Increase Efficacy
`Alison Palkhivala
`September 22, 2008
`
`Comment
`Comment
`
`EDITORS' RECOMMENDATIONS
`
`Cognitive-Behavioral Therapy
`Improves Fatigue in MS Patients
`
`MS Patients May Benefit From Yoga
`
`To Stay, or Not to Stay, on
`Natalizumab in MS
`
`Topic Alert
`Receive an email from Medscape
`whenever new articles on this topic are
`available.
` Add Multiple Sclerosis to My Topic
`Alert
`
`RELATED DRUGS & DISEASES
`
`Brain Imaging in Multiple Sclerosis
`
`Multiple Sclerosis
`
`Neuro-Ophthalmologic
`Manifestations of Multiple Sclerosis
`
`PrintPrint
`
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`September 22, 2008 (Montreal, Quebec) — Doubling the dose of
`glatiramer acetate from 20 to 40 mg/mL did not improve clinical or
`imaging outcomes after a year of therapy in patients with multiple
`sclerosis (MS).
`
`Both doses of the drug performed very well, although the higher
`dose appeared to reduce the number of gadolinium-enhancing and
`new T2 lesions on magnetic resonance imaging (MRI) sooner,
`according to research presented here at the World Congress on
`Treatment and Research in Multiple Sclerosis: 2008 Joint Meeting
`of the American, European, and Latin America Committees on
`Treatment and Research in Multiple Sclerosis (ACTRIMS,
`ECTRIMS, LACTRIMS). Lead author Giancarlo Comi, MD, a
`professor of neurology and chair of the neurology department at
`the University Vita Salute, Scientific Institute San Raffaele, in
`Milan, Italy, presented the results.
`
`For the phase 3 trial multicenter FORTE trial, 1155 patients with
`definite MS, based on revised McDonald criteria, were randomized
`to treatment with 20 mg/mL or 40 mg/mL of glatiramer acetate
`administered once daily by subcutaneous injection for 12 months.
`All patients had experienced at least 1 documented relapse in the
`year prior to screening or 2 relapses in the 2 years prior to
`screening and had an Expanded Disability Status Scale score
`between 0 and 5.5. They were followed up at months 1, 2, 3, 6, 9,
`and 12. The primary end point was the rate of confirmed relapse.
`
`Overall, 91% of those on the low dose of the drug and 86% on the high dose completed 12 months of therapy.
`Based on an intent-to-treat analysis, after 12 months of therapy, the rate of confirmed relapse was 0.33 with
`the low dose and 0.35 with the high dose (P = 0.4859). Similarly, there was little difference between the 2
`groups with respect to the proportion of relapse-free patients, the number of T1 gadolinium-enhancing lesions,
`the number of T2 lesions, and the amount of brain atrophy.
`
`"We expected that doubling the dose would significantly increase the effect, and this is not true. End of story,"
`Dr. Comi told Medscape Neurology & Neurosurgery. "But we had 2 positive aspects of the trial, with a
`tremendous amount of patients — [nearly] 1200 patients — with both doses. If you look at the change from
`baseline to the end, there was a 70% drop in the MRI activity. So, if we need a confirmation that glatiramer
`acetate is very active, this is the confirmation. Previous studies had [only] 200 to 300 patients."
`
`In addition, the higher dose of the drug affected the MRI findings more quickly. "With the high dose, there was
`an anticipation of the effect," said Dr. Comi. "By the end of the third month, it didn't matter which dose you
`had, you are in the same condition. However, you accumulate more lesions in the first 3 months with the low
`dose than with the high dose. So, if you want to have a quicker response to the treatment, then the high dose
`may have some advantages."
`
`Notably, the higher dose was just as safe as the lower dose, with only a small amount of increased treatment
`discontinuation due to injection-site reactions with the higher dose. Given that both doses are safe, Dr. Comi
`suggested that it might be useful to give some patients the higher dose for only a month or 2. "Sometimes
`patients start with very active disease, and you are afraid to wait 2 to 3 months to have a complete effect," he
`said.
`
`Enough is Enough?
`
`http://www.medscape.com/viewarticle/580865
`
`01/06/2015
`
`Page 1 of 2
`
`YEDA EXHIBIT NO. 2128
`MYLAN PHARM. v YEDA
`IPR2015-00644
`
`
`
`Page 1 of 2
`
`MULTISPECIALTY
`
`Medscape Conference Coverage, based on selected sessions at the:
`World Congress on Treatment and Research in Multiple Sclerosis: 2008 Joint Meeting of the American,
`European, and Latin America Committees on Treatment and Research in Multiple Sclerosis (ACTRIMS,
`ECTRIMS, LACTRIMS)
`This activity is not sanctioned by, nor a part of, ACTRIMS, ECTRIMS, or LACTRIMS. Conference news does not receive grant support
`and is produced independently.
`
`Medscape Medical News
`Doubling the Dose of Glatiramer Acetate Does Not
`Increase Efficacy
`Alison Palkhivala
`September 22, 2008
`
`Comment
`Comment
`
`EDITORS' RECOMMENDATIONS
`
`Cognitive-Behavioral Therapy
`Improves Fatigue in MS Patients
`
`MS Patients May Benefit From Yoga
`
`To Stay, or Not to Stay, on
`Natalizumab in MS
`
`Topic Alert
`Receive an email from Medscape
`whenever new articles on this topic are
`available.
` Add Multiple Sclerosis to My Topic
`Alert
`
`RELATED DRUGS & DISEASES
`
`Brain Imaging in Multiple Sclerosis
`
`Multiple Sclerosis
`
`Neuro-Ophthalmologic
`Manifestations of Multiple Sclerosis
`
`PrintPrint
`
`MOST POPULAR ARTICLES
`According to PHYSICIANS
`
`1. Best Evidence Yet!: Ejaculation
`Reduces Prostate Cancer Risk
`
`2. Statins Linked to Diabetes and
`Complications in Healthy Adults
`
`3. Evidence From Randomised Controlled
`Trials Did Not Support the Introduction
`of Dietary Fat Guidelines in 1977 and
`1983
`
`4. Low Vitamin D Tied to Testosterone Dip
`in Healthy Men
`
`5.
`
`'Morbid and Deadly' Drug Combinations
`to Avoid
`
`VIEW MORE
`
`September 22, 2008 (Montreal, Quebec) — Doubling the dose of
`glatiramer acetate from 20 to 40 mg/mL did not improve clinical or
`imaging outcomes after a year of therapy in patients with multiple
`sclerosis (MS).
`
`Both doses of the drug performed very well, although the higher
`dose appeared to reduce the number of gadolinium-enhancing and
`new T2 lesions on magnetic resonance imaging (MRI) sooner,
`according to research presented here at the World Congress on
`Treatment and Research in Multiple Sclerosis: 2008 Joint Meeting
`of the American, European, and Latin America Committees on
`Treatment and Research in Multiple Sclerosis (ACTRIMS,
`ECTRIMS, LACTRIMS). Lead author Giancarlo Comi, MD, a
`professor of neurology and chair of the neurology department at
`the University Vita Salute, Scientific Institute San Raffaele, in
`Milan, Italy, presented the results.
`
`For the phase 3 trial multicenter FORTE trial, 1155 patients with
`definite MS, based on revised McDonald criteria, were randomized
`to treatment with 20 mg/mL or 40 mg/mL of glatiramer acetate
`administered once daily by subcutaneous injection for 12 months.
`All patients had experienced at least 1 documented relapse in the
`year prior to screening or 2 relapses in the 2 years prior to
`screening and had an Expanded Disability Status Scale score
`between 0 and 5.5. They were followed up at months 1, 2, 3, 6, 9,
`and 12. The primary end point was the rate of confirmed relapse.
`
`Overall, 91% of those on the low dose of the drug and 86% on the high dose completed 12 months of therapy.
`Based on an intent-to-treat analysis, after 12 months of therapy, the rate of confirmed relapse was 0.33 with
`the low dose and 0.35 with the high dose (P = 0.4859). Similarly, there was little difference between the 2
`groups with respect to the proportion of relapse-free patients, the number of T1 gadolinium-enhancing lesions,
`the number of T2 lesions, and the amount of brain atrophy.
`
`"We expected that doubling the dose would significantly increase the effect, and this is not true. End of story,"
`Dr. Comi told Medscape Neurology & Neurosurgery. "But we had 2 positive aspects of the trial, with a
`tremendous amount of patients — [nearly] 1200 patients — with both doses. If you look at the change from
`baseline to the end, there was a 70% drop in the MRI activity. So, if we need a confirmation that glatiramer
`acetate is very active, this is the confirmation. Previous studies had [only] 200 to 300 patients."
`
`In addition, the higher dose of the drug affected the MRI findings more quickly. "With the high dose, there was
`an anticipation of the effect," said Dr. Comi. "By the end of the third month, it didn't matter which dose you
`had, you are in the same condition. However, you accumulate more lesions in the first 3 months with the low
`dose than with the high dose. So, if you want to have a quicker response to the treatment, then the high dose
`may have some advantages."
`
`Notably, the higher dose was just as safe as the lower dose, with only a small amount of increased treatment
`discontinuation due to injection-site reactions with the higher dose. Given that both doses are safe, Dr. Comi
`suggested that it might be useful to give some patients the higher dose for only a month or 2. "Sometimes
`patients start with very active disease, and you are afraid to wait 2 to 3 months to have a complete effect," he
`said.
`
`Enough is Enough?
`
`http://www.medscape.com/viewarticle/580865
`
`01/06/2015
`
`Page 1 of 2
`
`YEDA EXHIBIT NO. 2128
`MYLAN PHARM. v YEDA
`IPR2015-00644
`
`
`
`Doubling the Dose of Glatiramer Acetate Does Not Increase Efficacy
`
`Page 2 of 2
`
`Asked for comment on these findings, session moderator Askel Siva, MD, a professor of neurology at Istanbul
`University Cerrahpasa School of Medicine, in Turkey, told Medscape Neurology & Neurosurgery that he
`disagreed with this last assessment, however. "How much are we really gaining from 1 or 2 months [with a
`higher dose of glatiramer acetate]? I'm not sure," he said. "Maybe treating these patients with something else
`at the beginning would do the same thing or even more."
`
`"It seems that there might be a certain dose [for all MS medications at which you attain] satiety in the
`receptors," Dr. Siva concluded. "Then, enough is enough, and you don't need more. The current dose of
`glatiramer acetate that we are treating our patients with is enough."
`
`This study was funded by Teva Pharmaceutical Industries. Dr. Comi has received personal compensation for
`consulting and speaking from Novartis, Teva Pharmaceutical Industries, Sanofi-Aventis, Merck-Serono,
`Biogen-Dompè, Admiral, and Bayer Schering.
`
`World Congress on Treatment and Research in Multiple Sclerosis: 2008 Joint Meeting of the American,
`European, and Latin America Committees on Treatment and Research in Multiple Sclerosis: Abstract 79.
`Presented September 20, 2008.
`
`Comment
`Comment
`
`Commenting is limited to medical professionals. To comment please Log-in.
`Commenting is moderated. See our Terms of Use.
`
`Medscape Medical News © 2008 Medscape
`
`Cite this article: Alison Palkhivala. Doubling the Dose of Glatiramer Acetate Does Not Increase
`Efficacy. Medscape. Sep 22, 2008.
`
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`MORE
`
`http://www.medscape.com/viewarticle/580865
`
`01/06/2015
`
`Page 2 of 2
`
`YEDA EXHIBIT NO. 2128
`MYLAN PHARM. v YEDA
`IPR2015-00644
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