Teva Pharmaceuticals is not only hurting ProNeuron Biotechnologies and its rights. It's hurting the public of patients suffering from neuro-degenerative diseases.

How? According to all the preclinical data in the possession of ProNeuron and Teva itself, the clinical trial Teva is conducting is doomed to fail, or unfortunately, to produce results that are not optimal in the treatment of degenerative conditions of the nervous system.

Harsh words about Teva, which is the most highly-esteemed company on the Tel Aviv Stock Exchange. Worse, they appear in ProNeuron's lawsuit, delivered to the Tel Aviv District Court on Wednesday. Note ye that Teva owns 13.3% of the startup.

ProNeuron wants the court to terminate its agreement with Teva, dating from 2003 and updated in 2005. It hopes the court will give it back exclusive rights to continue developing the drug to treat neuro-degenerative conditions.

The lawsuit could well hurt Teva's image, and also sales of Copaxone, its proprietary treatment for relapsing/remitting multiple sclerosis, which generated sales of $1.4 billion in 2006.

If ProNeuron proves its claims, Teva could be in a sticky legal situation, and possibly also face a class action by shareholders, patients with MS and patients taking part in clinical trials to treat ALS - amyotrophic lateral sclerosis, better known as Lou Gehrig's disease -  a degenerative, fatal meuromuscular condition.

Molecular story

The whole thing started with an agreement between Teva and Yeda in 1986. Yeda commercializes intellectual property developed at the Weizmann Institute. It licensed Teva to use a molecule called COP-1 to develop a treatment for MS.

Ten years later, Yeda gave ProNeuron a license to use COP-1 to develop drugs to treat neuro-degenerative diseases, which are characterized by the death of nerve cells and gradual impairment of the body's control systems. The symptoms can range from forgetfulness to the loss of cognitive ability, as in the case of Alzheimer's, or blindness, as in glaucoma.

The initiative to ask Yeda for the license was based on the studies of Prof. Michal Schwartz, who studied people with glaucoma. She found that COP-1 has neuro-protective capabilities when administered at low doses, when given once a week, or even once a month. Copaxone, which is based on COP-1, is given frequently - every day - to MS sufferers.

Her finding could have implications for the treatment of MS and Teva's income from Copaxone.

ProNeuron claims that subsequent to the Yeda license, it carried out studies and preclinical trials at a cost of tens of millions of dollars, which proved the molecule's efficacy in treating neuro-degenerative diseases.

It claims to have proven that when COP-1 is given at low doses, it protects patients from certain neuro-degenerative conditions.

These studies, ProNeuron claims, were behind the interest Teva showed in buying ProNeuron's knowhow and intellectual property. In 2003 Teva and ProNeuron, and Teva, ProNeuron and Yeda, signed agreements, under which ProNeuron gave Teva a secondary license to use COP-1 to develop and commercialize a molecule to treat neuro-degenerative diseases.

Low doses

Teva and ProNeuron subsequently set up a joint venture and determined milestones for the development of the drug, and royalties to ProNeuron.

ProNeuron claims that one of Teva's fundamental undertakings, based on the 2005 agreement, was to start clinical trials to test the efficacy of the drug, no later than October 2006. The agreement stated that Teva could defer the deadline to October 2007, if it paid ProNeuron $5 million compensation.

The two companies cooperated on preclinical trials, which aimed to identify the specific neuro-degenerative disease that the first-phase clinical trial would target.  They also sought to identify the optimal drug regimen to treat the disease with the greatest efficacy and lowest risk.

ProNeuron claims that the results of the preclinical trials they did for five years clearly indicated that the molecule and its derivatives (including Copaxone) were effective, using models of glaucoma and Huntington's disease - but only when given in low doses. The molecule proved ineffective in ALS models. MS patients are given daily injections of Copaxone.

Improvisations

ProNeuron thought the results of the preclinical trials would serve as a base on which to plan and carry out the clinical trials, based on Teva's undertakings. But reality was otherwise.

It claims that in February 2006, Teva negotiated to delay starting the trial by a year, arguing that based on the preclinical results, it couldn't start the clinical trials as planned.

Teva explicitly stated during the negotiations that it had no indication indicating the efficacy of the molecule to treat ALS, ProNeuron claims.

To ProNeuron's surprise, it says, a few days later, Teva told it that it means to start clinical trials of COP-1 to treat ALS, though the preclinical trial results were adverse. Moreover, Teva meant to test daily administration of the drug, as given to MS patients. ProNeuron however argued that a daily  regime had failed all preclinical tests, and that everybody agreed it was unsuitable to treat neuro-degenerative diseases.

Teva changes its spots

ProNeuron also claims that Teva provided no explanation for its conduct, which was characterized by bad faith and extreme unreasonableness.

The startup may have shed light on Teva's conduct, mainly in that the drugs giant changed its spots: it had declared to ProNeuron that it was not prepared to conduct the clinical trial based on its undertaking from 2005, but then suddenly wanted to start the trial immediately, regarding ALS.

The secondary licensing agreement ProNeuron signed with Teva in 2005 ruled that after the clinical trial began, ProNeuron would lose its right to terminate the agreement in the event of breach by Teva. In that event, the only remedy to which it could aspire, would be to sue for compensation.

What that means is that the moment Teva began the clinical trial, ProNeuron would be at its mercy regarding further development and commercialization of a drug or drugs based on COP-1.

ProNeuron also claims that Teva's decision to start a trial that had been hastily put together, rather than planned properly, was designed to create failure. It would then gain three things, ProNeuron argues:

1. ProNeuron would lose its right to terminate the licensing agreement, as said above.

2.  If Teva had carried out a properly planned trial that worked, and found for instance that low dosages of Copaxone - weekly, let's say - were better in the treatment of neuro-degenerative disease, it could impair future sales of Copaxone. It might also have found that a weekly shot of Copaxone is as effective as daily shots.

3. Teva would have saved millions in the form of compensation to ProNeuron if it neglected to start the clinical trial by the deadline.

ProNeuron claims that Teva tried to distinguish Copaxone for drugs, by trying to find a new derivative of COP-1 to treat neuro-degenerative diseases through weekly injection, or monthly. Copaxone as said is given every day.

Bad for patients

The startup charges that Teva started testing a molecule called TV5010, a derivative of COP-1 with a higher molecular weight. The trial failed, ProNeuron says.

Teva found that TV5010 had not reached a level of development that allowed clinical trials to start by the time it had undertaken, namely October 2006. Also, the attempt to distinguish Copaxone did not work out, because the test results showed no difference between treatment with TV5010 and Copaxone.

Teva itself reported in its financial statement for the year 2006 that the TV5010 trial, administered by weekly subcutaneous injection, was halted at the end of 2006.

ProNeuron claims that Teva's failure to distinguish Copaxone put Teva into a conflict of interest, between its desire to maximize Copaxone sales, and its contractual duty toward the startup, to conduct a properly planned clinical trial process that would prove the efficacy of the drug in treating neuro-degenerative diseases.

Teva, says ProNeuron, preferred to protect Copaxone, and commenced a hastily thrown-together experiment that aimed at an unsuitable therapeutic target, and in a manner that assured ? based on the preclinical results ?it would fail.

Not only did Teva hurt ProNeuron and its rights: it also hurt the public of people with neuro-degenerative diseases, the startup argues. It knew the test would fail or be sub-optimal and might even shorten the life of the test subjects. And now ProNeuron wants its rights to the molecule back.

Source: Haaretz.com Copywrite 2010 Haaretz Newspapers (21/06/10)

The FDA denied the second petition for the same reason as the first attempt, because it would be "premature and inappropriate" to grant Teva's requests, but gave a detailed response that rejects many of the company's arguments against the generic approval.

Momenta Pharmaceuticals Inc. and Mylan Inc. have both filed to produce generic versions of Copaxone, a process that is likely to span years. The drug, one of the world's best selling multiple sclerosis treatments and an important part of Teva's business.

Copaxone was approved in 2006. In 2009, sales of Copaxone rose 25% to $2.8 billion and overall sales since 2002 have totaled $11 billion. Copaxone recorded revenue of $796m for the first quarter of 2010, up 28% on the corresponding quarter of 2009.

Teva has sued both Momenta and Mylan, triggering an automatic 30-month stay on FDA approval, which is required by a generics-related law, meaning no generic version of Copaxone can enter the US market until early 2011.

Source: Globes [online] © Copyright of Globes Publisher Itonut (1983) Ltd. 2010 (14/05/10)

Teva Pharmaceutical Industries, Ltd. announced that Copaxone® (glatiramer acetate injection), has now achieved one million patient years of experience in the treatment of relapsing-remitting multiple sclerosis (RRMS). This analysis is based on internal data submitted annually to the U.S. Food and Drug Administration (FDA).

"This milestone underscores the established long-term efficacy and safety of Copaxone® to physicians and patients who rely on the therapy to manage MS," said Kenneth Johnson M.D., professor of neurology, University of Maryland School of Medicine. "As the treatment landscape evolves, recognizing the importance of demonstrated efficacy and safety, over the long-term, remains paramount. The long-term Copaxone® data accumulated over the years is reassuring given the life-long nature of MS."

"Twenty years ago, we did not know if a safe, effective treatment for MS would be available for patients," said Douglas Franklin President & Chief Executive Officer, Multiple Sclerosis Association of America. "The fact that we are able to celebrate the long-term impact of this treatment is something we are thankful for on behalf of MS patients worldwide."

Approved in 1996, Copaxone® was the first, non-interferon treatment for RRMS. A prospective, clinical trial of more than 19 years is still ongoing and its data reinforce the established efficacy and safety profile of Copaxone®.

Laura Kimball, an RRMS patient, who participated in the pivotal study that led to the approval of Copaxone® and continues to be treated in the ongoing prospective study, says, "I believe that addressing my disease early and committing to a continuous therapy has helped me maintain a healthy and active lifestyle." Laura Kimball became a member of Team Copaxone® to share her journey as a person with MS and to inspire other patients.

"Hearing stories about patients benefiting from Copaxone®, reinforces our passion to serve the MS community," said Moshe Manor, Teva's Group Vice President, Global Branded Products. "Teva is committed to the MS community and continues to research new treatment options for MS, as well as invest in product enhancements aimed at improving patient comfort and compliance with Copaxone®."

Source: Medical News Today © 2010 MediLexicon International Ltd (14/04/10)

Teva Pharmaceuticals said it has filed a lawsuit to block rival drugmaker Mylan Pharmaceuticals from launching a generic version of its multiple sclerosis drug.

Mylan previously announced its intent to launch a generic version of Copaxone, a preventive treatment for the autoimmune disorder, which causes movement problems.

Teva said in a statement that the patents on the drug are protected through May 2014. The Israeli company filed a patent infringement lawsuit against Mylan in the U.S. District Court for the Southern District of New York.

The filing of a lawsuit automatically prevents the Food and Drug Administration from approving the generic version for 30 months or until a court decision is handed down. Drugmakers routinely file patent infringement lawsuits to delay the launch of generic versions of their drugs.

Generic drugs sell for as much as 80 percent less than the original branded drug.

Source: The Washington Examiner Copywrite The Washington Newspaper Publishing Company LLC (19/10/09)

Teva Pharmaceutical Industries Ltd. announced the Food and Drug Administration approved the multiple sclerosis drug Copaxone as a preventative treatment for the condition.

Multiple sclerosis is an autoimmune disorder that causes neurological problems, with symptoms including muscle weakness and spasms and difficulty in speech and coordination.

The drug is already approved to treat relapsing-remitting multiple sclerosis, where new symptoms occur suddenly or older symptoms become worse. The expanded approval allows for the drug's use in people who have experienced a first episode of multiple sclerosis and have magnetic resonance imaging results consistent with the condition.

Copaxone is already approved for similar uses in Europe.

In 2008, global sales of the drug rose 32 percent to $2.26 billion, making up about 20 percent of company's overall revenue during the year.

Source: Forbes.com Copyright 2008 Associated Press (04/03/09)

Teva Pharmaceutical Industries Ltd's multiple sclerosis drug Copaxone has been approved for early use in European patients.

The UK's Medicines and Healthcare products Regulatory Agency (MHRA) cleared an expanded label for the injectable drug to include the treatment of patients with a first clinical event suggestive of multiple sclerosis (MS).

The move triggers a simultaneous green light in 24 European Union member countries under the bloc's "mutual recognition" procedure.

Wednesday's approval allows Teva to sell the drug as a treatment for neurological symptoms that can indicate multiple sclerosis, with the aim of stopping the disease from developing. The drug is given after patients experience an episode called clinically isolated syndrome.

CIS patients can experience vision problems, weakness in the arms or legs, numbness or unusual sensations, speech impairment and memory loss, among other problems. Some are at high risk for developing multiple sclerosis.

In clinical trials, Teva said patients who were treated with Copaxone after experiencing CIS were 45 percent less likely to develop multiple sclerosis than patients who received a placebo.

A similar application to expand Copaxone's label to include early use is currently under review by the U.S. Food and Drug Administration.

Source: Forbes.com 2009 Forbes.com LLC & Reuters © Thomson Reuters 2009 (05/02/09)

Teva Pharmaceutical Industries Ltd. announced the launch of a new, thinner, 29-gauge pre-filled syringe for its multiple sclerosis  treatment, Copaxone, or glatiramer acetate injection.

A recent survey of 562 MS patients found the new thinner needle was significantly preferred by 77% of patients over the previous 27-gauge needle.

The survey also found that approximately two out of three participants experienced less pain while using the thinner needle and almost half of the participants had a better experience dealing with injection-site reactions.

Source: Teva Pharmaceutical Industries Ltd (23/12/08)

Teva Pharmaceutical Industries Ltd sued Swiss drugmaker Novartis AG and Momenta Pharmaceuticals Inc on Thursday, accusing them of infringing patents on its multiple sclerosis drug Copaxone.

Israel-based Teva had said in July it intended to sue after the Sandoz unit of Novartis applied to U.S. regulators to sell a generic version of the medicine.

The lawsuit, filed in U.S. District Court in Manhattan, claims that any generic version of Copaxone infringes patents that Teva contends are valid and enforceable.

Teva, itself a large maker of generic drugs, has maintained it has patent protection on Copaxone in the United States until May 2014 and in much of Europe until 2015.

Cambridge, Massachusetts-based Momenta said last month that the generic Copaxone application asserts that Teva's patents are invalid.

Copaxone, known chemically as glatiramer acetate, is an injected medicine that had U.S. sales of $1.1 billion last year.

A Sandoz spokesman said the company would not comment on pending litigation. Momenta could not immediately be reached for comment.

Teva is seeking to have the court declare that the defendants have infringed its patents, and that any approval of a Novartis generic not be granted until after Teva's patents expire.

The suit also seeks to prevent Novartis and Momenta from any commercial manufacture or sale of a generic Copaxone.

It asks the court to order Sandoz to withdraw its application seeking to sell the generic and award Teva monetary damages and interest to compensate it for misappropriation of Teva trade secrets as well as any further monetary relief the court deems just and proper.

Source: Yahoo! News © 2008 Yahoo! Inc. (29/08/08)

First, it is alleged that Teva tested Copaxone on amyotrophic lateral sclerosis patients despite the failure of the drug in previous trials on mice. However, the company vouched for the safety of the drug citing the successful trials it has conducted previously for developing the drug for multiple sclerosis.

But the Israel's health ministry appointed a special committee to probe a trial of the multiple sclerosis drug as an internal investigation by the health ministry's comptroller found that the company did not submit all the necessary information before trial approval. The special committee will check for any irregularities in the Teva data.

But Teva maintains that it has patent protection on Copaxone in the US until May 2014 and in most of Europe until 2015. Teva said that it will file a lawsuit against the two companies to prevent them from making a generic version of its drug. It also said that it will sue both Momenta and Sandoz for patent infringement.

Teva is reportedly facing another challenge from Mylan which has licensed a version made by India's Natco Pharma.

Source: Trading Markets.com © 2008 The Connors Group, Inc. (16/07/08)

Source: Teva Pharmaceutical Industries Ltd. (30/04/08)

Israel's Teva Pharmaceutical Industries said on Tuesday it expects its Copaxone to become the leading drug for multiple sclerosis worldwide in 2008.

"As we see the numbers of market share for competitors we believe that in 2008 we will also become the global leader," President and Chief Executive Shlomo Yanai told a news conference.

Copaxone overtook Biogen Idec Inc's Avonex as the leading MS treatment in the United States in mid-2007.

Source: Yahoo! Malaysia Copyright © 2008 Yahoo! Singapore Pte. Ltd. (12/02/08)

Teva Pharmaceutical Industries Ltd. announced today, in conjunction with the release of the Sanofi-Aventis group's financial results, that global in-market sales of Copaxone® in the third quarter of 2006 grew by 15% as compared to the third quarter of 2005 and reached a record of $354 million.

According to IMS, in the US Copaxone® continues to outpace the market growth strengthening its leadership position with TRx and NRx shares increasing to 34% and 35.2% respectively, as of September 2006. U.S. sales in the third quarter of 2006 increased 10% over the third quarter of 2005 to $226 million.

Outside the U.S., mainly in Europe, Copaxone® is the fastest growing multiple sclerosis therapy with growth of 26% over the third quarter of 2005, reaching sales of $128M.

Source: Teva Pharmaceutical Industries Ltd.(31/10/06)

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