Copaxone and glatiramer acetate
Teva Pharmaceutical Industries Ltd has asked the U.S. Supreme Court to stop a lower court ruling from going into effect while the justices consider an appeal in a patent fight over Teva's top-selling multiple sclerosis drug Copaxone.
On March 31, the high court agreed to hear Teva's appeal of a July 2013 ruling by the U.S. Court of Appeals for the Federal Circuit in favor of two teams developing cheaper generic forms of Copaxone: one involving Novartis AG's Sandoz Inc and Momenta Pharmaceuticals Inc, and the other involving Mylan Inc and Natco Pharma Ltd.
The appeals court had upheld some of the nine patents involved in the drug, or portions of them, but declared several invalid, meaning patent protections were set to expire in May 2014 instead of September 2015.
The company's lawyers said in the court filing that if the appeals court ruling was not stayed, "Teva's innovative and widely prescribed treatment for multiple sclerosis will lose protection."
The Supreme Court will not be hearing oral arguments in the Teva case until its 2014 term begins in October. A ruling could come as late as June 2015. If the court does not act on the stay application, the ruling could come "effectively too late to prevent irreparable harm to Teva," the lawyers said.
The stay application was directed to Chief Justice John Roberts. He is likely to ask the other litigants for a response before deciding how to proceed.
Teva is currently trying to switch patients over to a new version of Copaxone, which is the company's most important product.
The case is Teva v. Sandoz, U.S. Supreme Court, 13-854.
Source: Reuters © Thomson Reuters 2014 (09/04/13)
As the world’s largest maker of generic drugs, Teva Pharmaceutical Industries has been critical of brand-name manufacturers that try to block generic versions of their high-priced medicines.
But Teva is now emulating its rivals, mounting an aggressive effort to stave off generic versions of Copaxone, its big-selling brand-name drug for multiple sclerosis, which is set to lose patent protection late in May.
On Monday, Teva got help from the United States Supreme Court, which agreed to hear its appeal of a lower-court ruling that invalidated a patent that would have protected Copaxone until September 2015.
Teva, based in Israel, is desperate to stave off generic competition to Copaxone, which had global sales last year of $4.3 billion; $3.2 billion of that figure came from the United States. The drug, which has been on the market for 17 years and is the best-selling treatment for M.S., accounts for about 20 percent of Teva’s revenue and about half its profit.
But a generic version of Copaxone could provide needed cost relief to the health care system. The list prices of Copaxone and other older M.S. drugs have roughly quadrupled over the last decade, to about $60,000 a year.
“The prices would go up 10, 20, 30 percent at a time for no apparent reason,” said Dr. John R. Corboy, co-director of the Rocky Mountain Multiple Sclerosis Center at the University of Colorado. “We spend a quarter, some days half our time talking to patients about insurance and figuring out how we are going to get them medications.”
At the same time, Teva has been frantically trying to convert patients to a new, more concentrated form of Copaxone that requires patients to inject themselves only three times a week instead of every day. That new form would not be subject to generic competition. Once patients convert, it would be harder for insurers to force them to use a generic that would require them to go back to daily injections.
Teva has also submitted one petition after another to the Food and Drug Administration claiming, in essence, that Copaxone has such a complex makeup that it is virtually impossible to demonstrate that a copy is the same as the original. Subtle differences could make a generic less effective or even dangerous.
Ten years ago, Aventis, now part of Sanofi, made the same complexity argument about its blood thinner Lovenox.
In that case, Teva was on the other side, trying to introduce a generic. It accused Aventis of “blatant and unjustified efforts” to deny consumers “the cost savings associated with robust and fair generic competition.” The F.D.A. approved Teva’s generic.
Teva says Copaxone, which is known generically as glatiramer acetate, is more complex than Lovenox. It rejected suggestions it was being hypocritical in trying to block generic versions of Copaxone.
“I think it would be hypocritical if there would not be quality and efficacy and safety issues for patients here,” Dr. Robert Koremans, president of Teva’s specialty medicines division, said in an interview.
Copaxone is made up of four amino acids linked in chains of various sizes and sequences. It is not clear how the drug works, but it does reduce the frequency of M.S. relapses. The disease results from attacks on the protective covering of nerves by the body’s own immune system, causing symptoms like blurred vision and difficulty walking.
The F.D.A. has not yet approved a generic version of Copaxone, perhaps because of its complexity. But two teams have said they are confident the agency will approve their drugs as early as May. One team consists of Momenta Pharmaceuticals and Sandoz, the generic arm of Novartis. The other is Mylan and Natco Pharma.
The companies declined to comment Monday on whether they would still start selling their drugs given the Supreme Court’s decision to hear Teva’s appeal. But Craig A. Wheeler, the chief executive of Momenta, said last week that it “shouldn’t change things in my view.”
Sailesh K. Patel, an intellectual property lawyer in Chicago who is not involved in this case, said the generic companies could face damages if they market their products now and Teva ultimately prevails.
Even if the generics get to market by late May, Teva hopes by then to have converted 30,000 of the roughly 85,000 American Copaxone users to the new version of Copaxone, which was approved by the F.D.A. in late January.
To do that, Teva has expanded the staff of its patient support operation, Shared Solutions. The organization has made “thousands of phone calls” to patients and doctors, Dr. Michael Hayden, Teva’s chief scientific officer, said at an investor conference in late February.
Shared Solutions has also been holding complimentary dinners for patients. Two patients who attended a buffet dinner at a Mexican restaurant in Downey, Calif., on Thursday said they would switch to the new Copaxone, enticed by having only three injections a week.
“I just signed my paper right now,” said one of them, who gave her name only as Linda A.
Teva has set the price of the new Copaxone at $4,641 a month, lower than the older, daily version, which costs $5,060 monthly.
The conversion is “nicely ahead of plan,” Dr. Koremans said.
But there is some resistance. Excellus BlueCross BlueShield in upstate New York is requiring that a switch to the new Copaxone be medically necessary, not just for convenience. It hopes to keep patients on the daily version so their prescriptions would be automatically switched to a generic, saving employers money.
In six petitions to the F.D.A. since 2008 Teva has said, among other things, that generics should not be approved without clinical trials, something not usually required.
Synthon, a Dutch company that is developing a generic, just completed such a trial showing its drug was as good as Copaxone in reducing brain lesions. Synthon says European regulators want such trials. But the F.D.A. has not required them.
Source: The New York Times © 2014 The New York Times Company (01/04/14)
Synthon announces successful outcome of the Phase III GATE study with its generic glatiramer acetate(27/03/14)
NIJMEGEN, the Netherlands--(BUSINESS WIRE)--Synthon today announced that the company’s glatiramer acetate met the main endpoint of a late-stage study in patients with relapsing remitting multiple sclerosis (RRMS). The Phase III Glatiramer Acetate clinical trial To assess Equivalence with Copaxone®* (GATE) is to-date the only Phase III study conducted with a generic version of Copaxone® and has demonstrated an equivalent efficacy and safety profile for Synthon’s glatiramer acetate compared to Copaxone®.
GATE was set up following Scientific Advice received from the European Medicines Agency (EMA) with the aim to show equivalence of Synthon’s glatiramer acetate (Synthon GTR) with Teva’s Copaxone® in a well-controlled 3-arm double-blind study that was also designed to show superiority of the two active treatment groups over placebo. The large-scale, multicenter study consists of a nine-month double-blind efficacy comparison followed by a currently ongoing 15-month open-label extension and runs in Europe (including Russia, Ukraine and Belarus), Mexico, South Africa and the United States. “The data gathered during the double-blind part of the study present a solid basis for the regulatory submission in Europe in order to make an equivalent alternative to Copaxone® available to patients suffering from multiple sclerosis”, commented Jacques Lemmens, Synthon’s chief executive officer.
In the GATE study 796 patients with active RRMS were randomized to daily injections of Synthon’s glatiramer acetate (20 mg/ml), Copaxone® (20 mg/ml) or matching placebo for a double-blind 9-month treatment period. Primary endpoint of the study was the number of T1 gadolinium enhancing brain lesions on MRI assessed after 7, 8 and 9 months of treatment which were convincingly shown to be equally reduced in both the Synthon GTR as well as the Copaxone® treatment groups and significantly reduced compared to placebo. Other outcomes, including the incidence of MS relapses, disability, and patient reported tolerability, support the primary conclusion of the study. Safety analyses showed a comparable incidence of reported adverse reactions between both active glatiramer acetate groups.
Following the double-blind phase of the trial, patients in the Copaxone® and placebo groups of the GATE study switched over to Synthon GTR and are continuing Synthon GTR treatment for another 15-month period, as are the patients in the Synthon GTR arm of the study. This part of the study is expected to further confirm efficacy and safety of long-term Synthon GTR treatment as well as to provide evidence supporting the safety of switching therapies from Copaxone® to Synthon’s GTR. Jeffrey Cohen, M.D., Professor in the Cleveland Clinic Lerner College of Medicine, Director of Experimental Therapeutics at the Cleveland Clinic Mellen MS Center, and Chair of the GATE Steering Committee, remarked that “these are important results. The mechanism of action of Copaxone® is not fully understood and the resulting complexity of developing a generic alternative/version is broadly acknowledged. Clinically proven equivalence will ensure that patients with multiple sclerosis are provided with an effective and safe alternative.”
Concludes Lemmens: “Glatiramer acetate is the first anticipated generic version of an approved MS product in the United States and the European Union. The future availability of a generic of Copaxone® means that MS treatments – which currently cost between USD 30,000-60,000 per patient per year – will become more affordable, thereby allowing more MS patients around the world to have access to this medication.”
Full details of the study will be submitted for publication in a peer-reviewed medical journal and presented at future scientific meetings.
Synthon has already submitted an Abbreviated New Drug Application (ANDA) for glatiramer acetate, 20 mg/ml solution for injection in pre-filled syringes to the United States FDA in November 2011.
*Copaxone® is a registered trademark of Teva Pharmaceutical Industries Ltd.
Source: ©2014 Business Wire (27/03/14)
The U.S. Supreme Court deferred a decision on whether to hear an appeal by Teva Pharmaceutical Industries Ltd. that aims to delay generic competition to its top-selling Copaxone multiple-sclerosis drug.
The justices took no action on Teva’s bid for a hearing and are now scheduled to consider the case at their March 21 private conference, according to the court’s public docket.
Teva is seeking to revive a patent that would protect Copaxone from generic rivals until September 2015. Without that patent, Teva will lose legal protection this May on Copaxone, which brings in $3.2 billion in annual U.S. sales and accounts for more than half the company’s profit.
Teva is battling drugmakers that are planning to offer generic versions in May: Momenta Pharmaceuticals Inc, which has developed a version with Novartis AG’s Sandoz, and Mylan Inc.
The court issued a list of orders today from its March 7 conference. The Teva case was originally scheduled for consideration at that conference. The court, which often defers decisions on pending appeals, is scheduled to issue its next set of orders on March 24.
A ruling last year by the U.S. Court of Appeals for the Federal Circuit upheld four Teva patents that expire in May while invalidating a separate patent that would have blocked generic competition until September 2015.
In November, Chief Justice John Roberts refused to put the Federal Circuit ruling on hold while the high court decided whether to take up Teva’s appeal.
The case is Teva v. Sandoz, 13-854.
Source: Bloomberg ©2014 BLOOMBERG L.P (11/03/14)
FDA approves three-times-a-week Copaxone(29/01/14)
Teva Pharmaceutical Industries Ltd. has announced that the U.S. Food and Drug Administration (FDA) has approved the Company's supplemental new drug application (sNDA) for three-times-a-week Copaxone 40mg/mL, a new dose of Copaxone . This new formulation will allow for a less frequent dosing regimen administered subcutaneously for patients with relapsing forms of multiple sclerosis (MS). In addition to the newly approved dose, daily Copaxone 20 mg/mL will continue to be available. The daily subcutaneous injection was approved in 1996.
"The availability of three-times-a-week Copaxone 40 mg/mL is a significant advancement for patients as they now have the option of effective and safe treatment with Copaxone , while reducing the number of injections by 60 percent," said Omar Khan, M.D., Professor of Neurology and Chair of the Department of Neurology, Wayne State University School of Medicine, Detroit, MI. "Patients in the U.S. can now benefit from an improved dosing regimen without compromising the known benefits of Copaxone."
The FDA approval is based on data from the Phase III Glatiramer Acetate Low-Frequency Administration (GALA) study of more than 1400 patients, which showed that a 40 mg/mL dose of Copaxone administered subcutaneously three-times-a-week significantly reduced relapse rates at 12 months and demonstrated a favorable safety and tolerability profile in patients with relapsing-remitting MS.
"For more than 20 years, Teva has pursued its multiple sclerosis research with the goal of providing effective, safe and tolerable therapies for MS patients," said Larry Downey, President, North America Specialty Medicines. "We have progressively invested in the innovation of Copaxone in an effort to understand the needs and to ease the burden of patients who live with relapsing forms of MS every day. Today we are proud to continue to deliver on that investment by offering the freedom to dose three-times-a-week with Copaxone 40 mg/mL."
Source: The Wall Street Journal Copyright ©2014 Dow Jones & Company, Inc (29/01/14)
Teva Pharmaceutical has licensed rights to commercialize glatiramer acetate to Takeda Pharmaceutical in Japan as part of their agreement signed earlier in 2013.
Currently both the firms are working on additional agreements for implementation of the license.
Developed by Teva, glatiramer acetate for injection is indicated for the relapse prevention of multiple sclerosis and is marketed under the brand name Copaxone.
The drug is considered standard treatment for relapsing-remitting multiple sclerosis including patients who have experienced a first clinical episode and have MRI features consistent with multiple sclerosis.
It is currently approved in 55 countries worldwide, including the US, Russia, Canada, Mexico, Australia, Israel, and all European countries.
Under the deal, Teva will grant Takeda commercialization rights in Japan, and Takeda will submit a New Drug Application (NDA) for registration of glatiramer acetate in Japan.
Both the firms will work together to provide a new treatment options to patients with multiple sclerosis in Japan as early as possible, where the current available therapies are still limited.
Source: PBR © PBR 2013. (06/12/13)
Mapi pharma patents new MS drug(22/11/13)
Once-a-month treatment for multiple sclerosis gains US patent – inching Israeli pharma company closer to the market.
Only three years after going into business in Ness Ziona, Israel, Mapi Pharma has won a US patent for a promising drug in its pipeline – a slow-release form of glatiramer acetate for treating multiple sclerosis (MS) symptoms just once a month.
“We believe in two to three years they could be in the final stage of development, and about three years to market,” says Mapi Pharma president and CEO Ehud Marom.
Informed by his background at Teva Pharmaceuticals, where he headed global operations for innovative drugs including Copaxone; at Peptor, where he led development of diabetes drug DiaPep; and at Gamida Cell, Makhteshim-Agan and Pharma Two B, Marom came to Mapi knowing exactly what he wanted to focus on.
“We started mainly at ‘eye level’ with technologies to improve patients’ quality of life,” he tells ISRAEL21c.
“For MS, we chose to do something to improve the life of the patient by developing a technology that can be injected once a month instead of daily.”
Mapi’s glatiramer acetate product uses the same active therapeutic agent as the currently used drug, just in a novel form.
“The idea is to let the active material release slowly — and not as it is done today, immediately — by coating the active material with polymers. This provides a better quality of life, it’s safer and more convenient, and improves compliance and efficacy,” says Marom. “The FDA is supporting this way of delivering drugs for people with chronic diseases.”
MS is a chronic, often disabling disease that attacks the central nervous system. Unpredictable symptoms include numbness in the limbs, paralysis and loss of vision. The global market for MS pharmaceuticals is estimated to be approximately $10 billion.
Clinical trials for efficacy are set to start in January in Israel, and then in European and US centers. “There is a high chance that the efficacy will be the same because we changed the formulation, not the active molecules,” he points out.
Source: ISRAEL21C © 2013 ISRAEL21C (22/11/13)
Pharmaceutical Industries Ltd.’s Copaxone multiple-sclerosis drug to generic competition in May.
The lower court ruling invalidated one of the company’s patents and shaved more than a year off the legal protection for Copaxone, a treatment that generated $2.25 billion in U.S. sales for Teva in 2011. Chief Justice John Roberts today rejected Teva’s request to put that ruling on hold while the court decides whether to take up Teva’s appeal.
The rebuff is a victory for the generic-drug makers challenging the Teva patents. Those include Momenta Pharmaceuticals Inc, which is developing a generic version with Novartis AG’s Sandoz, and Mylan Inc, which has said it expects to be on the market in May.
Teva, based in Petach Tikva, Israel, said in court papers that it would suffer “irreparable injury” if the lower court ruling remained in effect. Even if the court were to take up the company’s appeal, review wouldn’t take place until the nine-month term that starts in October 2014, Teva said.
“Because the key Teva patent that the Federal Circuit invalidated will expire in September 2015, proceedings on the merits in this court could easily consume most of the remaining life of the patent,” the company argued.
The generic-drug companies said the case would have been eligible for the court’s current calendar had Teva moved more quickly after the July 26 appeals court decision.
Competition “would greatly benefit multiple-sclerosis patients, who pay about $40,000 per year for Copaxone,” the companies argued.
Multiple sclerosis causes the immune system to attack the insulating tissue around nerve fibers. It stops nerve cells from sending signals, sapping patients’ energy, blurring their vision and slowly depriving them of mobility, balance and coordination. Copaxone is an injection designed to work with the body’s immune system to cut relapses of the disease.
The case is Teva v. Sandoz, 13A458.
Source: Bloomberg ©2013 BLOOMBERG L.P (14/11/13)
Glatiramer acetate (GA) is a mixture of synthetic peptides used in the treatment of patients with relapsing-remitting multiple sclerosis (RRMS). The aim of this study was to investigate the effects of GA therapy on the gene expression of monocytes.
Methods: Monocytes were isolated from the peripheral blood of eight RRMS patients.
The blood was obtained longitudinally before the start of GA therapy as well as after one day, one week, one month and two months. Gene expression was measured at the mRNA level by microarrays.
Results: More than 400 genes were identified as up-regulated or down-regulated in the course of therapy, and we analyzed their biological functions and regulatory interactions.
Many of those genes are known to regulate lymphocyte activation and proliferation, but only a subset of genes was repeatedly differentially expressed at different time points during treatment.
Conclusions: Overall, the observed gene regulatory effects of GA on monocytes were modest and not stable over time. However, our study revealed several genes that are worthy of investigation in future studies on the molecular mechanisms of GA therapy.
Author: Madhan Thamilarasan, Michael Hecker, Robert Hermann Goertsches, Brigitte Katrin Paap, Ina SchrÃ¶der, Dirk Koczan, Hans-Jorgen Thiesen,Uwe Klaus Zettl
Credits/Source: Journal of Neuroinflammation 2013, 10:126
Source: 7thSpace Interactive © 2013 7thSpace Interactive (18/10/13)
Teva Pharmaceutical Industries Ltd. announced further results from a long-term, open-label extension study of glatiramer acetate (GA). The extension study was designed to evaluate the long-term neurologic disease course, and the safety and efficacy of glatiramer acetate 20 mg daily, the therapeutic agent in Copaxone(R) (glatiramer acetate injection), which is indicated for reduction of the frequency of relapses in patients with relapsing-remitting multiple sclerosis (RRMS). Detailed study results will be presented at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in Copenhagen, Denmark during poster session P577 on October 3, 2013.
"To our knowledge, glatiramer acetate is the only treatment for multiple sclerosis that has been prospectively studied for nearly two decades in a continuously monitored, long-term study," said Dr. Michael Hayden, President of Global R&D and Chief Scientific Officer for Teva Pharmaceutical Industries Ltd.
In this analysis of 74 patients, the cumulative annualized relapse rate (ARR) over the study period was 0.2, with 24.3 percent of patients remaining relapse-free through the entire observation period. Additionally, 63.3 percent of enrolled patients stayed below EDSS 4, while 79.5 percent stayed below EDSS 6 throughout the course of the study. Advancement to secondary progressive MS (SPMS), defined by a greater than 1.0-point EDSS progression (or greater than 0.5 for patients with baseline scores greater than 6) sustained for greater than or equal to 12 months without relapse, was seen in 35 patients (47 percent). Adverse events (AEs) leading to study discontinuation with incidence greater than one percent over the 20-year observation period were largely related to site reactions, while incidence of serious AEs were notably low, with no unexpected findings.
About the open-label extension study
The open-label extension study is a long-term clinical analysis of patients that participated in the original 36-month, randomized placebo-controlled U.S. Glatiramer Acetate Trial. The objective of the extension study was to evaluate the long-term neurologic disease course, and the safety and efficacy of glatiramer acetate 20 mg daily, in patients with relapsing-remitting multiple sclerosis. Ongoing patients in this study were continuously treated with glatiramer acetate 20 mg daily for a mean of 19.3 years (SD=1.3, range 18-21) with an average disease duration of 27.3 years. Baseline assessments for each patient in this pooled analysis were taken at the start of GA therapy.
Source: Teva Pharmaceutical Industries Ltd (08/10/13)
Credit Suisse sees Copaxone sales falling from $4 billion annually to $400,000 in 2019 and predicts annual sales of over $1 billion for Laquinimod.
Teva Pharmaceutical Industries Ltd, branded drug Copaxone will be the main loser in the multiple sclerosis treatment shift which is currently underway, according to a report by Credit Suisse entitled "Multiple Sclerosis It's a Revolution."
The report says that Tecfidera, the oral multiple sclerosis treatment launched several months ago by Biogen will be the main winner.
Credit Suisse sees annual sales of Copaxone falling 90% from about $4 billion in 2012 to less than $400,000 in 2019. The main reasons for this are well known and have long been acknowledged by investors- competition from rival branded drugs that are new on the market such as Tecfidera, for which it sees sales of $5.2 billion annually by 2019, and Novartis's Gilenya, for which it predicts sales of $3.2 billion annually by 2019. Copaxone will also face competition from generic entries after its patent expires.
Credit Suisse does expect Laquinimod, Teva's oral treatment for multiple sclerosis, to come onto the market by 2017 but sees annual worldwide sales of only $428 million in the US and $649 million in the rest of the world by 2019.
Source: Globes [online], Israel business news © Copyright of Globes Publisher Itonut (1983) Ltd. 2013 (02/10/13)
Teva received good news this week with the decision by a UK court to uphold the company's patent for multiple scleroris (MS) treatment Copaxone.
The Court of Appeal for England and Wales agreed with an earlier decision by the UK's High Court to defend the patent for Copaxone (glatiramer acetate injection) after its validity was challenged by Mylan.
Mylan, through its subsidiary Generics [UK], had applied to revoked Teva's patent for Copaxone, which is approved to reduce the frequency of relapses in patients with relapsing-remitting multiple sclerosis, in order to market its own generic version.
Following the two court decisions, any generic launch in the UK seems unlikely to happen until May 2015, when the patent for Copaxone expires.
“Thousands of patients in the UK and elsewhere depend on Copaxone for relief in relapsing-remitting multiple sclerosis, and we are pleased that the English Court of Appeal has upheld the validity of the patent until its expiry in 2015,” said Teva's president and CEO Dr Jeremy Levin.
Teva, which primarily focuses on generics itself, will be keen to make the most of Copaxone, which is its leading innovative product, taking in nearly $4bn in 2012.
Times are tough for the drug, however, due to the looming patent expiry in 2015, as well as competition from oral drugs such as Novartis' Gilenya (fingolimod), causing the company to restructure its organisation to cope with declining revenues.
The UK patent decision will offer some brief respite for the company, but the overall picture is less positive, with the US District Court for the Southern District of New York dismissing claims that Mylan was in breach of four of Teva's patents covering Copaxone.
Mylan is also appealing an earlier court decision to uphold nine patents held by Teva on Copaxone, stating that if it were successful, it would be "clear … for launch upon receipt of final regulatory approval”.
Source: PMLive © PMGroup Worldwide Ltd 2013 (31/07/13)
Teva Pharmaceutical Industries' multiple sclerosis drug Copaxone will lose its patent protection in 2014 rather than 2015 because of a ruling from a U.S. appeals court Friday.
The U.S. Court of Appeals for the Federal Circuit issued its decision in a patent fight between Teva and rivals Sandoz and Mylan Inc.
The result is that a generic version of Copaxone can be launched in May 2014, a year early.
"We are very pleased with today's ruling and we expect that it will allow Mylan to launch its generic version of Copaxone on May 25, 2014," Mylan Chief Executive Heather Bresch said in a statement.
Teva and Sandoz did not immediately comment on the ruling.
Both Sandoz, a generic division of Novartis, and Mylan had notified the U.S. Food and Drug Administration that they wanted to bring out generic versions of Copaxone. Teva sued to block them and protect its patents.
Patents on Copaxone, which accounts for about 20 percent of Teva's sales and about 50 percent of its profit, had been set to expire in September 2015.
Source: Reuters © 2013 Thomson/Reuters (29/07/13)
Teva Pharmaceutical Industries Ltd. has announced that data from the Glatiramer Acetate Low-frequency Administration (GALA) study, published in the Annals of Neurology, show that a 40mg/ 1mL dose of Copaxone(R) (glatiramer acetate injection) administered subcutaneously three times per week significantly reduced relapse rates at 12 months and demonstrated a favourable safety and tolerability profile in patients with relapsing-remitting multiple sclerosis (RRMS). Currently, the approved dose for Copaxone(R) is 20mg/ 1mL, which is a once a day subcutaneous injection.
The GALA study, a multinational, phase III, double blind, placebo controlled study, was designed to evaluate the efficacy, safety and tolerability of an investigational 40mg/ 1mL dose of GA given three times a week over a period of 12 months for the treatment of RRMS.
The published data show that glatiramer acetate (GA) 40mg/ 1 mL injections administered three times a week reduced annualized relapse rates by 34.0% (p<0.0001), reduced the cumulative number of new and enlarging T2 lesions by 34.7% (p<0.0001) when measured at six and 12 months, and the cumulative number of gadolinium enhancing lesions by 44.8% (p<0.0001) when measured at six and 12 months, as compared to placebo in patients with RRMS.
"We are pleased with the positive data of the GALA study which may lead to meaningful benefits for RRMS patients," said lead study author Omar Khan, M.D., Professor of Neurology and Chair of the Department of Neurology, Wayne State University School of Medicine, Detroit, MI. "Copaxone(R) 40mg/ 1 mL given three times a week demonstrated a favorable safety and tolerability profile, with the overall frequency of adverse events comparable to those seen in the placebo group."
The most common adverse event in the GA group was injection site reactions (35.5% with GA vs. 5.0% with placebo).
About the Study
The objective of the GALA study was to assess the efficacy and safety of glatiramer acetate (GA) 40mg/ 1mL administered three times weekly (tiw) compared with placebo in patients with relapsing--remitting multiple sclerosis (RRMS).
This randomized, double-blind study was conducted in 142 sites in 17 countries. Patients with RRMS with at least one documented relapse in the 12 months before screening, or at least two documented relapses in the 24 months before screening, and an Expanded Disability Status Scale score <= 5.5, were randomized 2:1 to receive either subcutaneous (sc) GA 40mg/ 1mL tiw or placebo for 12 months.
Of 1,524 patients screened, 1,404 were randomized to receive GA 40mg/ 1mL sc tiw (n = 943) or placebo (n = 461). Ninety-three percent and 91% of patients in the placebo and GA groups, respectively, completed the 12-month study. GA 40mg/ 1mL tiw was associated with a 34.0% reduction in risk of confirmed relapses compared with placebo (mean annualized relapse rate = 0.331 vs 0.505; p < 0.0001). Patients who received GA 40mg/ 1mL tiw experienced highly significant reduction (p < 0.0001) in the cumulative number of gadolinium-enhancing T1 (44.8%) and new or newly enlarging T2 lesions (34.7%) at months 6 and 12. GA 40mg/ 1mL tiw was safe and well tolerated. The most common adverse events in the GA group were injection site reactions (35.5% with GA vs 5.0% with placebo).
Source: Teva Pharmaceutical Industries Ltd (01/07/13)
Teva Pharmaceutical Industries Ltd. announced that the US Food and Drug Administration (FDA) has accepted for review the company’s supplemental new drug application (sNDA) for Copaxone (glatiramer acetate injection) 40mg/ 1mL, a higher concentration dose of Copaxone that offers a less frequent three times a week dosing regimen administered subcutaneously for patients with relapsing-remitting multiple sclerosis (RRMS). Currently, the approved dose for Copaxone is 20 mg/ 1mL, which is a once a day subcutaneous injection.
"We are pleased that the US FDA has accepted for review our sNDA. If approved, Copaxone 40mg/ 1mL given three times weekly will offer patients and their physicians flexibility in choosing a dosing regimen that works best for them, built upon the proven efficacy and established safety track record that Copaxone offers," said Michael Hayden, MD, president of Global R&D and chief scientific officer, Teva Pharmaceuticals Industries Ltd. “With a strong heritage in MS research innovation, Teva continues to demonstrate its commitment to patients by developing new treatment options to benefit the RRMS community.”
Copaxone (glatiramer acetate injection) is indicated for the reduction of the frequency of relapses in relapsing-remitting multiple sclerosis, including patients who have experienced a first clinical episode and have MRI features consistent with multiple sclerosis. The most common side effects of Copaxone are redness, pain, swelling, itching, or a lump at the site of injection, flushing, rash, shortness of breath, and chest pain.
Copaxone is now approved in more than 50 countries worldwide, including the United States, Russia, Canada, Mexico, Australia, Israel, and all European countries.
Teva Pharmaceutical Industries Ltd. is a leading global pharmaceutical company, committed to increasing access to high-quality healthcare by developing, producing and marketing affordable generic drugs as well as innovative and specialty pharmaceuticals and active pharmaceutical ingredients.
Source: Pharmabiz.com Copyright © 2010 Saffron Media Pvt. Ltd (03/06/13)
Mapi Pharma, developer of complex bulk Active Pharmaceutical Ingredients (APIs), has been granted a US patent for a long acting depot formulation of glatiramer acetate, which is under the development as a once-a-month treatment for Multiple Sclerosis (MS).
The glatiramer acetate depot formulation is to be injected once-a-month under the skin or into a muscle for a prolonged release of the therapeutic agent.
Mapi Pharma president and CEO Ehud Marom said that the new patent strengthens the company's position that supports its business plan and advances the company one step closer to bringing MS patients an improved drug to be administered once-a-month.
MS is a chronic, often disabling disease that attacks the central nervous system whose symptoms include numbness in the limbs, paralysis and loss of vision that are unpredictable and differ from one person to another.
The global market for MS pharmaceuticals is estimated to be approximately $10bn, according to Mapi Pharma.
Source: PBR Drug Research Drug Delivery © PBR 2013. Part of Progressive Digital Media Group Plc (09/05/13)
Synthetic Biologics, Inc, a developer of synthetic biologics and innovative medicines for serious infections and diseases, announced today that the U.S. Patent & Trademark Office has issued U.S. Patent No. 8,372,826 entitled, Estriol Therapy for Multiple Sclerosis and Other Autoimmune Diseases, to the Regents of the University of California which includes claims to the use of the Company's drug candidate, Trimesta™ (oral estriol), in combination with glatiramer acetate injection (Copaxone®). Copaxone® is the number one selling drug for multiple sclerosis with approximately $4 billion in annual sales. Currently marketed exclusively by Teva Pharmaceutical Industries Ltd., Copaxone® is expected to face generic competition as certain patent terms begin to expire in 2014. Through its wholly owned subsidiary, Synthetic Biologics holds the exclusive worldwide license to U.S. Patent 8,372,826 and 6,936,599 and pending patents for multiple sclerosis and other autoimmune diseases covering the uses of its drug candidate, Trimesta™.
Trimesta™ is currently being utilized in combination with Copaxone® in a randomized, double-blind, placebo-controlled Phase II clinical trial for the treatment of relapsing-remitting multiple sclerosis in women. Lead Principal investigator, Rhonda Voskuhl, M.D., Director, University of California, Los Angeles (UCLA) Multiple Sclerosis Program, UCLA Department of Neurology, along with investigators at 14 other centers in the U.S., are administering either Trimesta™ (8 milligrams orally per day) in combination with Copaxone® (20 milligrams per day), or a placebo plus Copaxone® to patients enrolled in the trial.
"The claims in this new patent further expand Synthetic Biologics' coverage of our proprietary oral estriol product candidate, Trimesta™, to include its use in combination with the leading FDA-approved multiple sclerosis drug, Copaxone®," stated Jeffrey Riley, Chief Executive Officer at Synthetic Biologics. "We look forward to reporting the clinical results of this combination therapy after the relapsing-remitting multiple sclerosis patients complete their two years of dosing and monitoring scheduled for January 2014."
The 164-patient relapsing-remitting multiple sclerosis trial is fully enrolled and it is anticipated that the last patient will complete their last visit during January 2014. The primary outcome measure for the study is the rate of relapse between the placebo and treated groups at two years, an accepted FDA-approvable endpoint in MS. The clinical trial is supported by grants exceeding $8 million, awarded by the National Multiple Sclerosis Society in partnership with the National Multiple Sclerosis Society's (NMSS) Southern California chapter, and the National Institutes of Health.
About Synthetic Biologics, Inc.
Synthetic Biologics, Inc. (NYSE MKT: SYN) is a biotechnology company focused on the development of product candidates for serious infections and diseases. Synthetic Biologics is developing a biologic for the prevention of C. difficile infection, and a series of monoclonal antibodies for the treatment of serious infectious diseases, including pertussis and Acinetobacter. The Company is also developing a synthetic DNA-based therapy for the treatment of pulmonary arterial hypertension. In addition, the Company is developing a drug candidate for the treatment of relapsing-remitting multiple sclerosis (MS) and cognitive dysfunction in MS.
Copaxone® is a registered trademark of Teva Pharmaceutical Industries Ltd.
 Teva Pharmaceutical Industries Ltd. Form 20-F filed with the SEC for the year ended December 31, 2012.
Source: Rock Hill Herald Online Copyright The Herald 2013 (05/04/13)
A recent clinical trial found that interferonβ-1a (INF) and glatiramer acetate (GA), two of the most commonly prescribed drugs for multiple sclerosis (MS), provide no additional clinical benefit when taken together. While findings published today in Annals of Neurology, a journal of the American Neurological Association and Child Neurology Society, suggest that taking both INF and GA together was not superior to GA monotherapy in reducing relapse risk; the combination therapy does appear to reduce new lesion activity and total lesion volume.
The National Institute of Neurological Disorders and Stroke (NINDS) describes MS as a neuroinflammatory disease, which affects the central nervous system by attacking myelin, a substance found in nerve fibers. NINDS estimates that up to 350,000 individuals in the U.S. are diagnosed with MS, which affects twice as many women as men, with most symptoms appearing between the ages of 20 and 40. Experts believe this complex autoimmune disease may be caused by genetic and environmental factors.
"While there are a number of drugs to treat MS, our study is the first to investigate if the concurrent use of two drugs with different modes of action would provide any additional clinical benefit without side effects," explains lead author Dr. Fred Lublin, Director of the Corinne Goldsmith Dickinson Center for Multiple Sclerosis at Mount Sinai Medical Center in New York. "The CombiRx study was designed to assess whether IFN and GA in combination was more effective than either alone in reducing relapse of MS." The research team enrolled 1,008 participants from 68 sites in this double-blind, randomized, controlled phase III trial. Participants received IFN plus GA (499), IFN alone (250), or GA alone (259), with 30µg IFN administered intramuscularly weekly and/or 20 mg of GA injected daily. The groups were followed for three years to assess if the combination therapy reduced MS relapse rates.
Trial results found that the IFN plus GA combination did not lessen disease progression according to the Expanded Disability Status Scale (a measure of disability caused by MS) or show change in the Multiple Sclerosis Functional Composite (measure used during clinical trials to assess leg, arm, and cognitive function in MS patients) better than the individual agents over a three-year period. The combination therapy and GA alone were significantly better than IFN in reducing relapse risk. MRI findings also suggested that the IFN plus GA together were better in reducing new lesions (plaques) and total lesion accumulation than either drug alone.
Dr. Lublin concludes, "Combining two of the most commonly prescribed MS therapies did not produce significant clinical benefit, reducing relapse risk, during the three-year study period. We will continue to monitor this group to determine if the combination therapy displays positive results, particularly in reducing lesion activity, beyond the initial trial timeframe."
In a related editorial, Dr. Stephen L. Hauser, Department of Neurology Chair at University of California, San Francisco and Editor-in-Chief of Annals adds, "In the end, CombiRx was essentially a negative study, with the combination therapy doing no better than monotherapy in reducing MS relapse rate over three years. However, the continued follow-up of this group by Dr. Lublin and colleagues provides an opportunity to develop a comprehensive long-term history of MS -- assessing response to first-generation therapies, possibly predicting individual disease trajectories, and understanding of treatment response. CombiRx could emerge as a model for long-term assessment, not only in MS, but across clinical neuroscience."
This CombiRx study was funded by a grant from the NINDS -- a part of the National Institutes of Health.
Source: Science Daily Copyright © 1995-2012 ScienceDaily LLC (12/03/13)
Introduction: Glatiramer acetate (Copaxone), a polypeptide has been approved for treating patients with active relapsing-remitting multiple sclerosis.
Case Presentation: We report the first case of severe acute hepatitis after commencing treatment for multiple sclerosis with glatiramer acetate.
A 31-year-old female with multiple sclerosis presented with anorexia, lethargy and jaundice five weeks after commencing glatiramer acetate. She had never received beta-interferon treatment. Investigations revealed a bilirubin of 0.109 mmol/L (0.002-0.02 mmoL/L) and prothrombin time of 21 secs (9-15 secs). Her liver function tests were normal before commencing glatiramer acetate.
A liver biopsy performed approximately 6 weeks after commencement of glatiramer acetate showed predominantly centrilobular hepatocyte necrosis with portal-venous bridging, along with mild portal and interface hepatitis. The necrosis was not accompanied by an acute inflammatory or chronic inflammatory infiltrate.
The features were not suggestive of autoimmune hepatitis but consistent with drug toxicity. The liver tests returned to normal within 2 months after cessation of glatiramer acetate.
Conclusion: Physicians should be aware that glatiramer acetate can be associated with uncommon but yet significantly severe liver toxicity.
Source: Pubmed PMID: 22873505 (10/08/12)