HAWTHORNE, N.Y. (AP) – Acorda Therapeutics Inc. said Thursday the Food and Drug Administration delayed a ruling on its multiple sclerosis drug candidate Fampridine-SR by three months.

The agency was due to make a decision by Thursday, but the ruling is now due by Jan. 22, 2010.

Acorda said the FDA extended its review because it recently submitted new information on its risk evaluation strategy for the drug.

Acorda sent in the additional information following a meeting with an FDA panel on Oct. 14. The panel recommended that Fampridine-SR receive FDA approval.

View full post here: http://news.moneycentral.msn.com/provider/providerarticle.aspx?feed=AP&date=20091022&id=10582834

View full article here: http://www.mscare.org/cmsc/Informs-Glatiramer-Acetate-data.html

According to the press release, Teva will vigorously defend its COPAXONE® intellectual property rights against infringement wherever they are challenged and intends to pursue all relevant regulatory avenues via the FDA. Teva’s lawsuit has been filed within the 45-day period provided under the Hatch-Waxman legislation and will triggers a stay of FDA approval for the Mylan ANDA until the earlier of the expiration of a period of 30 months or a district court decision in favor of Mylan.

According to Teva, COPAXONE® is a highly-complicated product to develop and manufacture, and given the inability to fully characterize the active ingredients of COPAXONE®, the company doubts any generic applicant’s ability to demonstrate conclusively that the composition of its product is identical to that of COPAXONE®. In fact, Teva contends that any company that files an application for any glatiramoid substance, via an ANDA or 505(b)(2) application, should conduct full-scale, placebo-controlled clinical trials with measured clinical endpoints in MS patients to establish safety, efficacy and immunogenicity in this patient population. Internal research at Teva has indicated that even minor changes in the synthetic process and/or molecular weight distribution of a glatiramoid can have severe ramifications on the safety and mechanism of action of the product.

The patents covering COPAXONE® all seem exceptionally similar, which is not to be unexpected. The earliest patent, which appears to be the parent that spawned the others, explains that COPAXONE® is a drug used to treat multiple sclerosis, and is an apparently a significant improvement on the prior art. The patent explains:

Copolymer-1 is a synthetic polypeptide analog of myelin basic protein (MBP), which is a natural component of the myelin sheath. It has been suggested as a potential therapeutic agent for multiple sclerosis (Eur. J. Immunol. [1971] 1:242; and J. Neurol. Sci. [1977] 31:433). All references cited herein are hereby incorporated by reference in their entirety. Interest in copolymer-1 as an immunotherapy for multiple sclerosis stems from observations first made in the 1950’s that myelin components such as MBP prevent or arrest experimental autoimmune encephalomyelitis (EAE). EAE is a disease resembling multiple sclerosis that can be induced in susceptible animals.

Copolymer-1 was developed by Drs. Sela, Arnon, and their co-workers at the Weizmann Institute (Rehovot, Israel). It was shown to suppress EAE (Eur. J. Immunol. [1971] 1:242; U.S. Pat. No. 3,849,550). More recently, copolymer-1 was shown to be beneficial for patients with the exacerbating-remitting form of multiple sclerosis (N. Engl. J. Med. [1987] 317:408). Patients treated with daily injections of copolymer-1 had fewer exacerbations and smaller increases in their disability status than the control patients.

Copolymer-1 is a mixture of polypeptides composed of alanine, glutamic acid, lysine, and tyrosine in a molar ratio of approximately 6:2:5:1, respectively. It is synthesized by chemically polymerizing the four amino acids forming products with average molecular weights of 23,000 daltons (U.S. Pat. No. 3,849,550).

It is an object of the present invention to provide an improved composition of copolymer-1.

The Israel based Teva Pharmaceutical Industries Ltd. is among the top 20 pharmaceutical companies in the world and perhaps the leading generic pharmaceutical company in the world, which is in itself ironic. COPAXONE® sales totaled $2.3 billion in 2008, accounting for over 20% of total revenues for Teva. Moving forward COPAXONE® was expected to account for an even larger percentage of Teva’s revenues. Presently Teva pays French drug company Sanofi-Aventis royalties even though Teva is solely responsible for marketing in North America. Teva must pay Sanofi-Aventis royalties into 2010 as a result of a deal between the companies dating back to April 2008. Thus, at a time when COPAXONE® was to become far more important to Teva it would be potentially devastating to the company to face generic competition. For now at least Teva will enjoy the market to itself, at least for the next 30 months.

View full post here: http://www.ipwatchdog.com/2009/10/18/teva-sues-mylan-over-multiple-sclerosis-drug-copaxone%C2%AE/id=6712/

October 15, 2009, 6:36 AM

Buffalo physicians announced Wednesday that they have started a large study that could overturn thinking about the generally accepted cause for multiple sclerosis.

MS is believed to stem from an abnormal response of the body’s immune system directed against the fatty sheath that surrounds nerve fibers in the brain and spinal cord.

But no one knows for sure, and recent research suggests an altogether different explanation for the disabling disease — narrowing of the primary veins outside the skull, a condition called chronic cerebrospinal venous insufficiency, or CCSVI.

The narrowing restricts the normal outflow of blood from the brain, causing alterations in the blood flow patterns within the brain that eventually cause injury to brain tissue and degeneration of neurons, the researchers said.

“If we can prove our hypothesis — that cerebrospinal venous insufficiency is the underlying cause of MS — it is going to change the face of how we understand MS,” said Dr. Robert Zivadinov, director of the Buffalo Neuroimaging Analysis Center at Kaleida Health’s Buffalo General Hospital.

Zivadinov, principal investigator in the study, is also a University at Buffalo associate professor of neurology.

Such a finding may allow doctors to identify individuals born with the abnormalities before they develop MS symptoms, treat the problem and perhaps even prevent it.

About 400,000 Americans suffer from MS, and because no cure exists, there is intense interest in new insights and potential treatments. Zivadinov urged caution, saying the work remains very preliminary.

A 2009 study by an Italian researcher, Dr. Paolo Zamboni, of 65 people with MS and 235 people with no or other neurological disorders found a strong relationship between MS and signs of abnormal blood drainage in veins. Zivadinov took part in small follow-up studies.

The researchers here now plan a larger, more rigorously designed trial that will involve 1,600 adults and 100 children and include a look at other factors involved in the disease.

It could be that CCSVI interacts with environmental, genetic or infectious triggers to initiate an abnormal immune response and the degeneration of nerve tissue, Zivadinov said.

The National Multiple Sclerosis Society, in a recent statement, offered a cautious response to the new study, saying that many questions remain about how and when the obstruction of veins might play a role in damage to the nervous system seen in MS.

“At the present time,” the organization said, “there is insufficient evidence to suggest that this phenomenon is the cause of MS.”

View full post here: http://www.buffalonews.com/cityregion/buffaloerie/story/828345.html?imw=Y

By Angela Maas, Managing Editor

Another drug in the self-injected multiple sclerosis (MS) class recently came onto the marketplace. But many within the pharmaceutical industry are saying that other than giving Novartis an entry into the MS market before its oral MS therapy gains FDA approval, it is unclear what significant advantages the drug Extavia (interferon beta-1b) — identical clinically to Betaseron (interferon beta-1b), which has been on the market for more than 16 years — offers over the other products. And health plans are likely to react accordingly.

The self-injected MS specialty drugs — Avonex (interferon beta-1a), Rebif (interferon beta-1a), Betaseron and Copaxone (glatiramer acetate) — have an average wholesale price in the $2,500 to $3,000 per month range. Launched in 1993, Betaseron was the first of these players onto the marketplace. Schering AG, now Bayer Schering Pharma AG, acquired the rights to Betaseron in a deal with Chiron Corp. After Novartis acquired Chiron, Novartis and Bayer Schering worked out a deal allowing Novartis to seek approval for its own branded interferon beta-1b

So why is Novartis bringing another branded interferon beta-1b onto the marketplace?

“It may sound silly, but at a basic level, there does not appear to be any unmet medical need met by the introduction of Extavia — the reality is that Betaseron is already filling any need,” says Richard Tinsley, a partner at Putnam Associates, a pharmaceutical and biotechnology consulting firm. He adds that “we have not heard of any medical need or even drug transition strategy that would explain the introduction of a ‘me-too’ Betaseron.”

“We’re still trying to figure out exactly” what Novartis’ motivation was with Extavia, says Sean Karbowicz, Pharm.D., manager of clinical pharmacy services for RegenceRx, The Regence Group’s PBM.

Tinsley tells SPN that an MS physician he spoke with “hoped that Novartis might be looking to offer a price discount. I think most people would agree that Betaseron could have done better in the market had its marketing and launch strategies been designed differently.”

Heather Rose, a Novartis spokesperson, declined to disclose Extavia’s price, but she says it will be “the lowest-priced first-line injectable disease-modifying therapy for multiple sclerosis.” However, an industry insider who asked to not be identified tells SPN that the wholesale acquisition cost of Extavia is $2,459 per package — “per vial a little less” than the cost of Betaseron, which itself costs a little bit more than the other self-injectables. Aside from a “support program for Extavia users,” Rose adds, “as part of each monthly prescription, patients will receive 15 vials of Extavia, resulting in a net gain of 12 vials per year compared to other interferon beta-1b therapies — nearly a month of additional treatment for no additional cost.” Sara Deno, Pharm.D., director of clinical services at BioScrip, explains that Extavia will offer a 30-day supply, as opposed to a 28-day supply of Betaseron. Asked about the cost and packaging differences, Elizabeth Engelhardt, vice president of clinical services and product development at BioScrip, Inc., says Novartis “wasn’t very aggressive.”

Novartis Hopes to Have First Oral MS Drug

Most of the industry sources who spoke with SPN speculate that Novartis’ real interest in the MS market is not Extavia but rather FTY720 (fingolimod), an oral therapy that the company hopes will be the first orally administered MS drug to hit the marketplace. “The introduction of Extavia allows us to establish our presence in the MS market ahead of the planned introduction of other products for the treatments in MS,” says Rose, who adds that “Novartis has a significant commitment to multiple sclerosis.” Industry sources tell SPN that the company’s reasoning is entirely logical.

Extavia gives Novartis “their entrée into a particular market space where they have no experience,” says Nick Calla, vice president of trade relations for Walgreens Specialty Pharmacy. “There are a lot of nuances to dealing with” MS. According to Karbowicz, “There is some logic to this.…We’ve seen similar kinds of maneuvers in the past where a company will adopt” such an approach, particularly with some pain medications. Extavia “gives them a huge opportunity to get to know the [MS] players and understand the market,” adds Engelhardt.

A leading MS specialist from Miami who asked not to be identified contends that FTY720 is “a promising oral drug.” Rose tells SPN that the drug is in Phase III development and that the company’s plans to submit the drug for approval in both the U.S. and European Union by the end of this year “remain on track.” The company released initial results from a two-year study of the drug Sept. 30 that show “FTY720 reduced relapse rates by 54-60% compared to placebo, and disability progression by 30-32%.” Sources tell SPN that assuming everything goes as planned, the drug should hit the marketplace in late 2010 or early 2011.

Both Extavia and Betaseron are injected subcutaneously every other day, and the dose is the same. Debbie Stern, vice president of consulting firm Rxperts, Inc., notes that Rebif is subcutaneously injected three times a week, and Avonex is administered intramuscularly weekly. Copaxone is subcutaneously injected daily. Betaseron’s prescribing information notes that a prefilled, single-use syringe of the drug comes with a 30-gauge needle. Rose says that Extavia has a 27-gauge needle with its auto-injector. However, she adds, it is up to physicians as to what size they prescribe for a patient to use for self-injection. “The smaller needle size of Betaseron is one of their selling points,” says Stern. Rebif and Copaxone have 29-gauge needles. Avonex has a 23-gauge needle with a 25-gauge option.

The MS specialist says that Copaxone is the most prescribed of the MS self-injectables, with percentage market share in the upper 30s to around 40%. “The other 60% is divided among the interferons,” the source tells SPN. Engelhardt says that Rebif is probably the biggest competitor for Copaxone. Extavia is the third high-dose interferon available, with Avonex the sole low-dose interferon. The “gold standard” in the medical world is “a high-dose interferon or Copaxone” as a starting prescription, says Engelhardt. “Then it falls to patient preference and patient tolerability.” All of the drugs are fairly similar in terms of their clinical efficacy and their safety profiles, say sources interviewed for this article.

Physician Pickup of Extavia May Be ‘Minimal’

Stern projects that Extavia pickup among physicians will be “very minimal — Betaseron has the lowest national market share of all MS therapies, and it is unlikely that neurologists will switch their prescribing.” Tinsley adds that “without a financial incentive or a world-class patient program, I am not sure why physicians would prescribe the product. The Novartis sales force is likely to be new, which adds some complexity for rapid physician uptake. This applies not only to new patients but also — even more so — to switching existing patients.”

Rose would not disclose whether Novartis has any kind of deals for physicians, PBMs or other stakeholders designed to promote uptake of the drug. No one who spoke with SPN had heard whether any deals would be available. “One of the most fundamental challenges faced by pharma marketing organizations today,” says Tinsley, is “how do you differentiate a late-to-market — fourth entry in this case — ‘me-too’ product via clinical or financial strategies? If they do have something, it will be novel.”

Stern adds that “if the net price of Extavia is significantly lower than other interferons, I would expect that most payers would prefer Extavia to Betaseron, and some more controlling payers might list Extavia as preferred over other interferons.” She says that there is already product preferencing within this class of drugs. The fifth edition of the EMD Serono Injectables Digest, says Stern, shows that 67% of respondents from 69 payers have one or more preferred agents in the MS therapy class. Extavia “will find its place if plans want to be more aggressive with their contracting and product preferencing,” says Calla.

Lori McLaughlin, a spokesperson for WellPoint, Inc., tells SPN that the plan has not reviewed Extavia yet, and that it will be placed on the third tier of the payer’s three-tier formulary at this point. The other self-injectables are also on the third tier, but the plan has designated Avonex, Copaxone and Rebif as its preferred products. “We are able to offer these drugs at a better price to our members,” she explains. Both Extavia and Betaseron have a step edit requiring members to use both Avonex and Rebif first, she says. Karbowicz says that Regence has not looked at Extavia yet. It has prior authorization for Betaseron but not on Avonex and Rebif, the other interferons, he adds. “We don’t prefer Betaseron now anyway, so there would have to be a pretty significant reason for us to embrace” Extavia, he says.

According to Tinsley, “Assuming there is no clinical differentiation that has not been publicly disclosed and, without a price discount, Extavia will face a tough battle in the payer world. The current environment for ‘me-too’ products is difficult.” Based on a discussion with “a major plan,” he says that “Extavia will begin any negotiation on the third tier (possibly with restrictions) versus the other interferons on the second tier. Probably the best they could hope for is parity with the other interferons on the second tier.”

View full post here: http://www.aishealth.com/Bnow/hbd101609.html

* Committee Views Fampridine-SR as Safe, Effective and Clinically Meaningful for
Improving Walking in People with Multiple Sclerosis
* Conference Call Scheduled for Thursday, October 15 at 8:00 a.m. Eastern Time

HAWTHORNE, N.Y.--(Business Wire)--
Acorda Therapeutics, Inc. (Nasdaq: ACOR) today announced the U.S. Food and Drug
Administration (FDA) Peripheral and Central Nervous System Drugs (PCNSD)
Advisory Committee voted 12 to 1 that clinical data on Fampridine-SR 10 mg twice
daily demonstrated substantial evidence of effectiveness as a treatment to
improve walking in people with multiple sclerosis (MS) and voted 10 to 2 (1
abstention) that it is clinically meaningful and can be safe for use. 

"We are pleased with the outcome of today`s Advisory Committee meeting. People
with MS have an urgent need for therapies to improve their walking, which is
essential to conducting their activities of daily life. If approved,
Fampridine-SR would be the first medicine to improve walking in people with MS,"
said Ron Cohen, M.D., Acorda Therapeutics President and CEO. "This Advisory
Committee meeting is an important milestone in the development of Fampridine-SR,
and we look forward to working with the FDA as it completes its review of
Acorda`s New Drug Application." 

The Committee also recommended by a vote of 12 to 1 that Acorda be required to
evaluate the effects of doses lower than 10 mg twice daily, but by a 10 to 2
vote (1 abstention) that these studies not be required prior to approval. 

At the request of the FDA, the Committee discussed possible conditions for use,
including for patients with renal impairment or history of seizure. Acorda has
proposed a Risk Evaluation and Mitigation Strategy (REMS) program, which could
include healthcare professional and patient education around appropriate use of
Fampridine-SR. 

The FDA seeks the advice of an advisory committee such as the PCNSD when
evaluating a potential new treatment, but is not required to follow its
recommendation. The current Fampridine-SR Prescription Drug User Fee Act (PDUFA)
date set by the FDA is October 22, 2009; the PDUFA date is the target date for
the FDA to complete its review of Fampridine-SR. 

Conference Call

Acorda will hold a conference call and audio webcast on Thursday, October 15,
2009 at 8:00 a.m. ET to discuss the outcome of the Advisory Committee meeting.
To participate in the conference call, please dial 866-700-6979 (domestic) or
617-213-8836(international) and reference the access code 85689772. The
presentation will be available via a live audio webcast at: 

http://phx.corporate-ir.net/phoenix.zhtml?p=irol-eventDetails&c=194451&eventID=2484252

A replay of the call will be available from 11:00 a.m. ET on October 15, 2009
until midnight on November 14, 2009. To access the replay, please dial
888-286-8010(domestic) or 617-801-6888 (international) and reference the access
code 45457470. The archived webcast will be available for 30 days in the
Investor Relations section of the Acorda website at http://www.acorda.com. 

About Fampridine-SR

Fampridine-SR is a sustained-release tablet formulation of the investigational
drug fampridine (4-aminopyridine or 4-AP). In laboratory studies, fampridine has
been found to improve impulse conduction in nerve fibers in which the insulating
layer, called myelin, has been damaged. Fampridine-SR is being developed by
Acorda Therapeutics and manufactured by Elan Corporation plc. 

View full post here: http://www.reuters.com/article/pressRelease/idUS211700+14-Oct-2009+BW20091014

Moreover, IFN-beta and other available treatments must be given parenterally and have a variety of adverse effects. Certain naturally occurring flavonoids, such as luteolin, have anti-oxidant and anti-inflammatory effects, including inhibition of activated peripheral blood leukocytes from MS patients.

Luteolin also inhibits mast cells, as well as mast cell-dependent T cell activation, recently implicated in MS pathogenesis. Moreover, luteolin and structurally similar flavonoids can inhibit experimental allergic allergic encephalomyelitis (EAE), an animal model of MS in rodents.

An appropriate luteolin formulation that permits sufficient absorption and reduces its metabolism could be a useful adjuvant to IFN-beta for MS therapy.

Author: Theoharis Theoharides
Credits/Source: Journal of Neuroinflammation 2009, 6:29

View full post here: http://7thspace.com/headlines/322720/luteolin_as_a_therapeutic_option_for_multiple_sclerosis.html

In a late stage trial, Avanir was testing two doses of Zenvia against emotional outbursts in patients with multiple sclerosis and amyotrophic lateral sclerosis. The lower dose did not significantly reduce the number of those events compared to placebo, but the higher dose did, the company said.

In morning trading, Avanir shares rose 18 cents, or 7.8 percent, to $2.48.

The study tested Zenvia as a treatment for pseudobulbar effect, or emotional reactions such as uncontrollable laughing or crying. The condition is associated with some neurological disorders, including multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer’s disease, Parkinson’s disease, and damage caused by stroke or brain injury, Avanir said. The company said there are no approved treatments for the condition.

Avanir’s trial included 197 patients with ALS, or Lou Gehrig’s disease, and 129 with MS. Avanir said Zenvia did not lead to a statistically significant reduction in the severity of the outbursts. The higher dose of the drug also relieved multiple sclerosis related pain, Avanir said.

Zenvia is a combination of two drugs, dextromethorphan and quinidine. Dextromethorphan is also a common ingredient in cough and cold medicines because it can suppress coughing. Avanir is also testing Zenvia as a treatment for peripheral diabetic nerve pain.

The company said the drug was safe, and three patients left the 12-week study because of side effects. All of those patients were in the lower dose group. The most common side effects were dizziness, nausea, diarrhea, tiredness and colds.

View entire post here: http://www.google.com/hostednews/ap/article/ALeqM5grFeJN9K9BdDVlfVgbdXlDqfb4rwD9B7LI9O0

WASHINGTON — Shares of Acorda Therapeutics plummeted Friday after the Food and Drug Administration issued a negative opinion that questioned the safety and effectiveness of the company’s multiple sclerosis drug.

A panel of FDA advisers is scheduled to meet next week to vote on Acorda’s Fampridine-SR, which is designed to improve patients’ ability to walk. Multiple sclerosis affects the brain and nervous system, causing loss of balance, muscle spasms and other movement problems.

In briefing documents posted Friday, the FDA raised serious questions about whether the drug’s benefits outweigh its risks, which include seizures.

Acorda shares fell $4.76, or 21.4 percent, to close at $17.52 Friday. The company’s stock has traded between $14.42 and $29.27 in the past year.

Acorda conducted two trials tracking patients’ ability to complete a 25-foot walk. While both studies met their goal of showing that patients on the drug had a statistical improvement in walking ability compared with those on placebo, the actual time to complete the exercise did not improve.

“For these reasons, it appears the clinical meaning of the differences seen on the primary outcomes is in question,” according to the FDA review.

FDA scientists also noted an increased risk of seizures with the drug. The agency will ask its panel Wednesday whether the drug’s benefits outweigh its side effects, including both seizures and urinary tract infections.

The FDA is not required to follow the group’s advice, though it usually does.

Hawthorne, N.Y.-based Acorda stated in its own briefing documents that no evidence of seizures has been shown when the drug is given at the recommended 10-milligram dose. However, the company acknowledged that risks increase with higher doses.

“Patients and physicians should therefore be thoroughly informed about the risks of prescribing or taking higher than the proposed 10 mg dose,” the company said.

Deutsche Bank analyst Mark Schoenbaum said most specialists who treat the disease “do not seem phased,” by the drug’s seizure risk. In a research note to investors, Schoenbaum predicted the FDA panel will vote to approve the drug, but with a “black box” warning about seizures.

Acorda expects the FDA to complete its review of Fampridine-SR by Oct. 22.

View entire post here: http://www.google.com/hostednews/ap/article/ALeqM5jGSaOc4fVQDH9oRk3L7Qd7Ee9XVwD9B7RK6G0

The treatment, glatiramer acetate, marketed as Copaxone, was tested in 16 countries among 481 patients with a telltale lesion in the central nervous system called clinically isolated syndrome.

The volunteers either received the drug or a dummy lookalike for up to three years.

Copaxone reduced the risk of developing “clinically definite” MS by 45 percent compared with a placebo.

In addition, the time it took for 25 percent of patients to develop the full-scale disease was more than doubled in the Copaxone group, at just under two years on average compared with just under one year in the placebo group.

Around a million people around the world are affected by MS, a degenerative disease in which the immune system attacks myeline, the fatty sheath that protects nerve fibres.

As a result, signals between nerve cells are delayed, disrupted or even blocked, rather like a poor connection in an electrical wire.

This causes worsening problems in coordination and balance, as well as blurred vision and slurred speech.

“This study establishes glatiramer acetate as an option for patients with clinically isolated syndrome who choose to start treatment early to improve control of the underlying disease process,” says the new paper.

The study was led by Giancarlo Comi, a professor of neurology at Milan’s Vita-Salute University in Italy.

Copaxone is currently approved for treating “relapsing-remitting” forms of MS.

View full article here: http://www.google.com/hostednews/afp/article/ALeqM5hMp9AsbapJMeUGkb-ZYv457bhy4w