Israel-based Teva Pharmaceutical Industries Ltd. has announced that the U.S. Supreme Court has granted the Company’s Copaxone certiorari petition, and will hear its appeal of a decision from the United States Court of Appeals for the Federal Circuit that invalidated the claim of U.S. Patent 5,800,808 (the “’808 patent”).
The 808 patent expires on September 1, 2015 and claims a process for manufacturing the active ingredient of Teva’s relapsing-remitting multiple sclerosis (RRMS) product, COPAXON (glatiramer acetate injection) 20mg/mL. Teva says it is pleased that the Court has agreed to hear its appeal and that it remains committed to pursuing all options to protect its intellectual property for Copaxone — a costly drug that reduces frequency of relapses in patients with Relapsing-Remitting Multiple Sclerosis (RRMS), including patients who have experienced a first clinical episode and have MRI features consistent with MS.
Teva had previously prevailed in the District Court regarding nine Copaxone patents, including the ‘808 patent, and a ruling last year by the U.S. Court of Appeals for the Federal Circuit upheld some of the Copaxone patents that expire in May 2014, while invalidating the ‘808 patent that is the subject of Teva’s now-granted certiorari petition.
Any purported generic version of Copaxone would be required to obtain the Food and Drug Administration’s (FDA’s) approval prior to being made available to the public. Teva contends that the inability of generic version producers to fully characterize the active ingredients of the product leads many experts to believe that the only way to ensure the safety, efficacy and immunogenicity of any purported generic version of Copaxone would be through full-scale, placebo-controlled clinical trials with measured clinical endpoints (such as relapse rate) in RRMS patients.
There is some irony in that as the world’s largest maker of generic drugs, Teva Pharmaceutical Industries has in the past harshly criticized brand-name pharmaceutical manufacturers that attempted to block generic versions of their proprietary-branded and more expensive medicines. However, according to a report by the New York Times Business Day’s Andrew Pollackmarch, Copaxone, on the market now for 17 years, is the best-selling treatment for Multiple Sclerosis, sales of which represent roughly 20 percent of Teva’s revenue and account for about half the company’s profit.
Pollackmarch notes that availability of a generic analog of Copaxone could provide welcome cost relief to the health care system, noting that list prices of Copaxone and other older MS drugs have roughly quadrupled over the last decade, and currently cost about $60,000 a year per patient.
Teva says it is confident Copaxone will remain a proprietary, global market leading product for reducing the frequency of relapses in RRMS patients over the product’s lifecycle, given the strength of its intellectual property (IP) rights.
However, the company is also vigorously promoting a new Copaxone variant that was approved by the FDA in January, which reduces injection frequency to three times a week as opposed to daily, that would not be subject to generic competition, thus making it more difficult for health care insurers to insist that patients opt for once-a-day generics. Pollackmarch reports that Teva hopes to have converted some 30,000 of the approximately 85,000 American Copaxone users to the new version of Copaxone, as a possible hedge against generic competition should its Supreme Court appeal prove unsuccessful and generics are authorized for marketing after May 31. He notes that Teva has pegged the cost of the new Copaxone at $4,641 a month — lower than the older once-a-day version, which costs $5,060 per month.
However, MarketWatch’s Robert Daniel reports that Natco Pharma Ltd. of Hyderabad, India, for example, has said it would launch glatiramer acetate, the generic version of Copaxone, at about 40% of the price of the branded Teva drug.
Last July, Natco Pharma noted that the US Court of Appeals for the Federal Circuit ruling, had reversed a district court’s finding related to Teva’s US Patent for Copaxone, and would essentially mean that Natco could launch generic Copaxone through its marketing partner Mylan Inc. after May 2014, subject to FDA approval, and now of course to the result of Teva’s Supreme Court appeal. Natco observes that Copaxone is estimated to have generated revenues, in USA of about $3.45 Billion in 2012.
A Dec. 10, 2013 outlook report for non-GAAP financial performance for the full year ending December 31, 2014 was released by Teva Pharmaceutical Industries in an effort to enhance investor understanding of the business performance of the company, and to provide more clarity and transparency regarding its projections for 2014, given significant uncertainty concerning possible generic competition to Copaxone in the U.S. The Company accordingly provided two alternative scenarios for its current non-GAAP financial outlook for the year.
The “Generic Copaxone” scenario assumes the launch of at least two AP-rated generic competitors to Copaxone in the U.S. on June 1, 2014, while an “Exclusive Copaxone” scenario assumes no generic competition to Copaxone in the U.S. during 2014. Both scenarios assume the launch of Copaxone 40mg three-times-a-week in early 2014 and exclusive sales of the generic version of Pulmicort in the U.S. throughout 2014. The outlook provided is organic, and neither alternative includes the potential impact of any business development activities.
In the report, Teva estimates that each month of delay in the launch of generic competitors to Copaxone in the U.S. will contribute on average approximately $78 million to net revenues and $0.08 to non-GAAP diluted earnings per share.
“2014 will be a pivotal year for Teva and a year of major transitions across the company”, commented Eyal Desheh, Acting President and CEO of Teva. “We will continue to make significant progress in implementing our strategy. We will focus our efforts on our generics business and core R&D programs, including high-value complex generics, promising specialty medicines and New Therapeutic Entities. In our specialty business, we anticipate six important launches and the potential submission of ten additional medicines for approval. At the same time, we are focused on increasing our organizational effectiveness through our cost reduction program to ensure Teva’s leadership position, growth and sustainable profitability.”
Teva says Copaxone (glatiramer acetate injection) is thought to work by modifying the immune system. Relapsing-Remitting Multiple Sclerosis (RRMS) is most commonly known as a disease that affects the central nervous system (CNS), but it also involves another biological system — the immune system, which plays an important role in helping to maintain overall health. The immune system is a complex biological system made up of a network of cells, tissues, and proteins that all play a role in the body’s immune response. In RRMS, confused — or inflammatory — T cells attack the myelin that protects the axons, or nerve tissue, in the CNS.
In four major studies, Copaxone had demonstrated effectiveness in reducing the frequency of relapses in RRMS, as well as reducing some types of brain lesions seen on magnetic resonance imaging (MRI).
Teva observes that of the therapies approved to treat RRMS, as well as treatments currently being studied, are thought to have an impact on the immune system, but are respectively are thought to do so in different ways. Copaxone is thought to modify the immune processes believed to be responsible for activating MS, and consequently it may interfere with immune functions. For example, treatment with Copaxone may interfere with the body’s ability to recognize foreign invaders and defend against infection, and that while there is currently no known evidence that Copaxone reduces the body’s normal immune response, this has not been systematically evaluated.
Teva notes that before a drug can be sold, it is necessary to obtain a marketing authorization from the relevant regulator — a stamp of approval confirming that that the drug is of high quality, safe and effective. To obtain a marketing authorization, companies submit an application demonstrating that the drug consistently complies with legal and regulatory requirements and that any label claims are supported by robust scientific evidence.
To obtain a marketing authorization for a generic drug, it is necessary to demonstrate that it provides the same quality, efficacy and safety as the reference innovative drug. The application includes information on the composition of the drug and a detailed description of how the active pharmaceutical ingredient and drug product are manufactured and controlled. This ensures that every batch is consistently manufactured to the required quality and is stable when stored at the recommended conditions.
In addition, there is a detailed description of the drug’s development, including pharmaceutical, pre-clinical and clinical trials, to ensure that the drug is safe and efficacious. This often involves conducting studies with healthy volunteers, to demonstrate that the generic drug’s rate and extent of biological activity are the same as those of the innovative reference drug.
Obtaining a marketing authorization is, however, only the beginning of the process. Further obligations need to be fulfilled throughout the lifecycle of the drug, namely, monitoring the safety of the drug after launch.
Teva says it aspires to be first to market high quality, affordable, generic drugs, and that its generic medicines activities include:
• 73 pharmaceutical and API production facilities
• Approximately 149 product applications awaiting final FDA approval
• Approximately 62 first to file applications pending in the US
1,103 generic approvals in Europe, as of December 2012
• Over 2,131 marketing authorization applications pending approval in 30 European countries.
Generic drugs are typically sold at a substantially lower price than branded counterparts, since their development/approval process is relatively brief and less costly. These products contain the same active ingredients as found in the innovative drug, and meet similar regulatory requirements as the innovative drug. Reliance on generic drugs continues to grow due to the need to control healthcare costs, particularly given the increasing elderly population.
Teva Pharmaceutical Industries Ltd. says it constantly seeks to expand its generic portfolio, while concentrating on being first to introduce high-quality, affordable generic products into the market. When considering whether to develop a generic medicine, Teva takes into account R&D recommendations, manufacturing capabilities, regulatory and IP restrictions and commercial factors, and claims to have the largest generic R&D team in the industry, committed to providing high quality generic drugs.
Headquartered in Israel, Teva, as noted, claims to be the world’s leading generic drug maker, with a global product portfolio of more than 1,000 molecules and a direct presence in approximately 60 countries. Teva’s branded businesses focus on CNS, oncology, pain, respiratory and women’s health therapeutic areas as well as biologics. The company currently employs approximately 45,000 people around the world and sales reached $20.3 billion in net revenues in 2013.
Teva maintains that its medicines help patients and consumers in a way that few other companies can. Teva produces 73 billion tablets a year in 73 pharmaceutical and API facilities around the world. Some 2.7 million prescriptions are filled daily with Teva’s products in the EU, and an additional 1.5 million in the U.S. Teva affirms that the scale and breadth of its generics portfolio has an unprecedented impact on global healthcare, and that the company’s exceptional integration of generics and specialty R&D enables it to generate a robust pipeline of high-value medicines, with an emphasis on complex and branded generics. Teva’s R&D capabilities have expanded beyond tablets, capsules, liquids, ointments and creams to a broad range of effective dosage forms and delivery systems. In 2012 the company launched 450 generic products.
Teva says it has a unique understanding of — and footprint in — world markets, where its generic medicines are tailored to the needs of local patients, physicians and consumers. The company also claims to have an unparalleled ability to partner in commercializing generic products, particularly in emerging economies.
Teva Pharmaceutical Industries Ltd.
The New York Times
Natco Pharma Ltd.