Friday, March 21, 2008
Thursday, March 20, 2008 - 2:57 PM EDT
On the heels of a similar decision by the U.S. Food and Drug Administration, European regulators have concluded that patients should be warned about possible liver damage related to the Biogen Idec drug Tysabri.
Tysabri, which Massachusetts-based Biogen Idec (Nasdaq: BIIB) makes at a facility in Research Triangle Park, is a drug used to treat multiple sclerosis.
On Feb. 27, Biogen and its Irish partner on Tysabri, Elan Corp., posted a letter to the FDA's Web site. The letter, addressed to doctors, says patients have developed signs of liver injury as soon as six days after taking their first dose of the drug. It tells doctors that they need to monitor Tysabri patients for potential liver damage and warn them about the risk.
Now, the European Medicines Agency is addressing the issue. In a statement Thursday, it also says that Tysabri patients need to be monitored for and warned about liver damage.
Tysabri is Biogen's fastest-growing drug. It was pulled from the market in 2005 after it was linked to a rare but fatal brain infection. U.S. regulators allowed it to return under a monitoring program in 2006, however, after they decided that the drug's effectiveness outweighed its risks.
03.20.08, 12:44 PM ET
LONDON (Thomson Financial) - The European Medicines Agency EMEA has announced the labels for Elan and Biogen's Tysabri should include warnings about liver injury on its product information.
The EMEA's Committee for Medicinal Products for Human Use has requested that Elan (nyse: ELN - news - people ), the marketing authorisation holder for Tysabri, submits a variation to the marketing authorisation to implement these changes.
Last month Elan and Biogen announced some patients suffered liver injury after taking the multiple sclerosis treatment.
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LONDON, March 20 (Reuters) - The European Medicines Agency has recommended approval of Novartis' (NOVN.VX: Quote, Profile, Research) Extavia intended for treatment of people with multiple sclerosis, the London-based watchdog said on Thursday.
Recommendations for marketing approval by the agency's Committee for Medicinal Products for Human Use (CHMP) are normally endorsed by the European Commission within a couple of months.
The drug is the company's branded version of Bayer AG's (BAYG.DE: Quote, Profile, Research) Betaseron, interferon beta-1b, that gives Novartis an important presence in MS treatment before the anticipated submission of its once-daily therapy FTY720 (fingolimod).
Last March Novartis and Bayer settled a dispute over Betaseron in a deal that gave Bayer full control of the product while allowing Novartis to launch a version in 2009.
Multiple sclerosis affects more than an estimated 2.5 million patients worldwide and is one of the leading causes of neurological disability in young adults. (Reporting by Michael Kahn; Editing by Rory Channing)
© Reuters 2008 All rights reserved
Tuesday, March 18, 2008
The CEO of Biogen Idec told investors Tuesday that he expects to see more cases of a rare, fatal brain disorder in patients taking the drug Tysabri, Reuters reported Tuesday.
But James Mullen, the executive, thinks the problems are unlikely to create more regulatory problems for Tysabri, a multiple sclerosis drug pulled temporarily from the market in 2005 thanks to the brain disease.
James Mullen told investors that "we anticipate there will be some additional cases of PML," according to Reuters. PML is the abbreviation for the brain infection seen in two Tysabri patients three years ago. Biogen Idec (Nasdaq: BIIB), which makes the drug at a facility in Research Triangle Park, voluntarily pulled the treatment from the market.
Tysabri has since returned under a patient-monitoring program, however, with no new cases of PML. Biogen hopes to make it a blockbuster, billion-dollar drug by 2010.
New cases of PML in Tysabri patients could "create a lot of excitement in the short term given the history of this product," Reuters reported Mullen as saying. But the Biogen chief added that he would see "no regulatory problems." Many patients take Tysabri despite its risks because the drug is highly effective.
Biogen co-markets Tysabri with Elan Corp. of Ireland.
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Teva Pharmaceutical's Altered Peptide Ligand Copaxone Boasts the Greatest Patient Share Among First- and Second-Line Therapies for the Treatment of Mu
WALTHAM, Mass., March 11 /PRNewswire/ -- Decision Resources, one of the world's leading research and advisory firms focusing on pharmaceutical and healthcare issues, finds that Teva Pharmaceutical's Copaxone has the greatest patient share among first- and second-line therapies, and falls short of Merck Serono/Pfizer's Rebif (by 0.2 percent) in third-line treatment. However, in all three lines of therapy, the interferon-beta drug class (Biogen Idec's Avonex, Rebif, and Berlex's Betaseron) outpaces the altered peptide ligand drug class (consisting only of Copaxone) in patient share. Competition between the two drug classes is fiercest in first-line therapy.
"The low volume of patient share attributed to Avonex or Rebif compared with Copaxone in first- and second-line treatment illustrates a significant delay on the part of physicians and/or patients to engage in an interferon- beta therapy within a year of a patient's initial diagnosis for multiple sclerosis," said Madhuri Borde, analyst at Decision Resources. "However, the magnitudes of Rebif's first- and second-line patient shares suggest that some physicians are treating the disease more aggressively than might be expected, as this high-dose, high-frequency agent reaches patient shares close to and surpassing Avonex in first- and second-line treatment, respectively."
According to the new report entitled Treatment Algorithms in Multiple Sclerosis, neurologists note that Copaxone's better short-term and long-term side-effect/safety profile, together with its lower rate of induction of neutralizing antibodies, are critical reasons for choosing Copaxone instead of Avonex, Rebif and Betaseron. Although Copaxone is administered daily, 23-28 percent of neurologists we surveyed indicate that a key reason to prescribe the drug over any of the interferon-beta therapies is the drug's ability to foster greater patient compliance, an attribute that is closely tied to the Copaxone's lower incidence of flulike side effects.
About Treatment Algorithm Insight Series
Decision Resources combines in-depth primary research with the most extensive claims-based longitudinal patient-level data from PharMetrics(R) to provide exceptional insight into physicians' prescribing trends and the factors that drive therapy product choice, from diagnosis through multiple courses of treatment, for a specific disease.
For each disease examined, Decision Resources' Treatment Algorithm Insight Series provide the following:
-- Summary of U.S. medical practice based on interviews with leading experts in the field. -- Qualitative diagnosis/referral/treatment algorithm for the United States. -- Drug usage by lines of therapy (1st, 2nd, 3rd line). -- Discussion of key freeform combinations by lines of therapy. -- Product share (class and specific compound level) within each line of therapy (1st, 2nd, 3rd line). -- Progression of therapy from key 1st line products. -- Pathway to key therapies from previous therapies. -- Qualitative analysis of two-year forecast incorporating upcoming launches, changes in reimbursement, etc.
About Decision Resources
Decision Resources, Inc., (http://www.decisionresources.com/) is a world leader in healthcare market research publications, advisory services, and consulting designed to help clients shape strategy, allocate resources, and master their chosen markets.
All company, brand, or product names contained in this document may be trademarks or registered trademarks of their respective holders.
For more information, contact: Elizabeth Marshall Decision Resources, Inc. 781-296-2563 firstname.lastname@example.org
By Bill Kettler
March 10, 2008
When Destiny Marquez finds a good thing, she wants other people to know about it.
These days the Medford woman has been talking to anyone who will listen about a drug called naltrexone. It's been widely used to treat opiate addiction, but that's not what captured her interest.
Marquez came across naltrexone while she was trying to help her father, Bentley Lyon, who's been struggling with Parkinson's disease for 18 years. His symptoms had been increasing, and he started to decline rapidly after suffering a stroke during surgery.
A friend had told Marquez that she'd heard some Parkinson's patients were getting relief from their symptoms by taking extremely low doses of naltrexone, or LDN. Marquez and her mother, Elizabeth, balked. Although the drug had been tested and approved by the federal Food and Drug Administration for addiction treatment, it had never been tested for treating Parkinson's.
"We said 'No,' " Marquez recalled.
When Bentley's condition continued to deteriorate, mother and daughter asked him to give LDN a try. By then they had done some research on their own, and learned that the drug was gaining favor not only among Parkinson's patients, but also as a treatment for other diseases, including multiple sclerosis and Crohn's disease.
Marquez said her father started taking 3 mg a day late in 2004, far less than the 50 mg that's prescribed for addiction treatment.
"It was like a miracle," she recalled.
Marquez said the spasticity in her father's left leg disappeared over several days, and his caregiver said he stopped complaining about back pain.
Speech is difficult for Bentley, 78, a former Marine and marathon runner who worked as a forester and wrote two mystery novels, but he said LDN "stopped the progression" of his symptoms. Naltrexone apparently works by stimulating the body's own immune system, said Dr. Ian Zagon, a professor of neural and behavioral sciences at Pennsylvania State University.
"It's very simple," he said, "but it took a while to figure out."
Zagon said research over the past two decades indicates the body's immune system is orchestrated by its own naturally produced internal opioids. Large doses of naltrexone block the body's opioid receptors, eliminating the high derived from drugs. In extremely small doses, however, naltrexone seems to block the opioid receptors just long enough to prompt the body's hormone system to produce more of its own natural endorphins, which somehow encourages the immune system.
"We're working with the body's own chemistry," Zagon said. "This has nothing to do with chemotherapy."
The drug's off-label use began to grow just as the Internet became a major source of information exchange. There's now an LDN home page (www.lowdosenaltrexone.org), a Wikipedia entry, and forum pages where people exchange information and their own experiences with the drug.
Naltrexone's efficacy for Parkinson's or other autoimmune diseases could be established by subjecting it to a new round of clinical trials, the same rigorous, expensive, time-consuming studies that were performed when it was approved for addiction treatment. Unfortunately, there's little incentive for drug manufacturers to spend the money. Naltrexone has gone generic, and lost the patent protections that would make it a profitable drug for treating autoimmune diseases.
"It doesn't behoove the pharmaceutical companies to develop it," Zagon said.
As a generic drug, it's also incredibly cheap. Most patients can get it for about $1 a day.
Zagon would like to see someone provide the funding for new clinical trials for LDN, but in the meantime, some studies are already under way. The National Multiple Sclerosis Society has funded a study that will look at high- and low-dose naltrexone treatments in mice with a disease much like multiple sclerosis, and the National Institutes of Health has funded a phase II trial using LDN in patients with Crohn's disease. Phase II trials involve as many as several hundred people, but they fall short of the randomized phase III trials in which some people get the drug and others do not.
Marquez has seen how the drug has helped her father, and she hopes one day someone will do the research that will determine its efficacy.
"We're not the only family talking about this," she said. "We're trying to share this information because it buys you time.
"We've got to tell the world this drug is incredible."
Destiny Marquez can be reached by e-mail at: email@example.com
Reach reporter Bill Kettler at 776-4492 or e-mail: firstname.lastname@example.org
Preclinical profile and potential for lower cardiac toxicity drives investigator interest
SEATTLE, March 6 /PRNewswire-FirstCall/ -- Cell Therapeutics, Inc. (CTI) (Nasdaq and MTA: CTIC) announced today that its investigational drug pixantrone will be studied in a multicenter phase I/II trial initiated by the Fondation Charcot Stichting, in Brussels, Belgium, which sponsors a consortium of centers involved in studying new therapies for the treatment for multiple sclerosis. This study will enroll patients with aggressive relapsing remitting (RR) or secondary progressive (SP) multiple sclerosis (MS). Mitoxantrone, a related compound which is less active in preclinical studies, has been approved by the U.S. Food and Drug Administration (FDA) for the reduction of neurological disability and/or frequency of clinical response in patients with SP MS. A phase III trial with pixantrone in relapsed aggressive non-Hodgkin's lymphoma (NHL) is near completion.
"Despite the availability of newer biologic agents, drugs such as mitoxantrone remain an important therapy in relapsing MS. Long term cardiotoxicity remains a major drawback to treating multiple sclerosis with mitoxantrone and imposes a limitation both for selection of patients and for the duration of the treatment," said R.E. Gonsette, M.D., Chairman Fondation Charcot Stichting and principal investigator of the study. "In addition to the potential for lower cardiac toxicity, preclinical studies suggest that pixantrone may provide more effective immune regulation than mitoxantrone, the only currently approved cytotoxic agent for treating MS."
The investigator-sponsored trial (IST) will enroll 20 patients in Belgium, France and Germany.
About the Study
Twenty patients with aggressive RR MS or SP MS who failed to respond to approved immunomodulatory agents (interferons, glatiramer acetate) will be included. The objectives of the study are to determine the efficacy of pixantrone as an immunosuppressive agent based on its ability to decrease the lymphocyte count and to evaluate efficacy in MS based on gadolinium enhanced magnetic resonance imaging. This trial is an open-label, multi-center, non-comparative study of pixantrone administered at a dose of 120 mg/m2 once every 21 days (3 weeks). Four consecutive three-week courses of pixantrone will be administered in order to determine if this regimen results in lymphopenia of less than or equal to 1000/mm3. The doses and the number of infusions will be adapted to leukocyte, granulocyte and thrombocyte counts and possibly reduced.
Pixantrone (BBR 2778) is a novel DNA major groove binder that contains an aza-anthracenedione molecular structure, differentiating it from anthracycline chemotherapy agents. A new chemical compound for the treatment of non-Hodgkin's lymphoma (NHL), and various other hematologic malignancies, solid tumors, and immunological disorders, pixantrone is being developed by CTI to improve the activity and safety in treating cancers usually treated with the anthracycline family of anti-cancer agents. Anthracyclines have been shown to be very active clinically in a number of tumor types, such as lymphoma, leukemia, and breast cancer. For these diseases, anthracycline-containing chemotherapy regimens are effective in first-line (initial) treatment. However, they may cause cumulative heart damage that limits lifetime dosage and does not allow for retreatment. Pixantrone has been designed to reduce the potential for heart damage compared to currently available anthracyclines or anthracenediones without a loss in anti-tumor or immunomodulatory activities.
About Cell Therapeutics, Inc.
Headquartered in Seattle, CTI is a biopharmaceutical company committed to developing an integrated portfolio of oncology products aimed at making cancer more treatable. For additional information, please visit http://www.cticseattle.com.
This press release includes forward-looking statements that involve a number of risks and uncertainties, the outcome of which could materially and/or adversely affect actual future results. Specifically, the risks and uncertainties that could affect the development of pixantrone and the risks related to this clinical trial include risks associated with preclinical and clinical developments in the biopharmaceutical industry in general and with pixantrone in particular including, without limitation, the potential failure of pixantrone to prove safe and effective for treatment of multiple sclerosis, the identification of new risks or limitations of pixantrone that may be discovered in this Investigator Sponsored Trial, determinations by regulatory, patent and administrative governmental authorities, competitive factors, technological developments, costs of developing, producing and selling pixantrone, and the risk factors listed or described from time to time in the Company's filings with the Securities and Exchange Commission including, without limitation, the Company's most recent filings on Forms 10-K, 8-K, and 10-Q. Except as may be required by law, CTI does not intend to update or alter its forward-looking statements whether as a result of new information, future events, or otherwise.
SOURCE Cell Therapeutics, Inc.
Web site: http://www.cticseattle.com
Tuesday, March 04, 2008
By JANE E. BRODY
Published: March 4, 2008
When it comes to understanding, preventing and treating chronic diseases, multiple sclerosis ranks among the most challenging. The word “multiple” is apt in more ways than one.
Various suggested causes include early-life exposure to certain viruses or toxic agents, geographic and dietary influences, inherent immunological defects and underlying genetic susceptibilities.
MS is highly unpredictable. Rarely are any two patients alike in the presentation, duration and progression of symptoms; even the underlying cause of disability in MS is being reconsidered. And rarely do any two patients respond in the same way to a given therapy, be it medically established or alternative. Trial and error is the name of the game, experts say, because it is often not possible to know in advance what will work best for individual patients.
These are the frequent underpinnings of confusion and distrust among those afflicted and their families. They sometimes give rise to claims that the organizations raising large amounts of money to support research and patient services and the scientists studying the disease have no intention of finding a cure, lest it put them out of business. It is a ridiculous notion on its face, since many of those involved in fund-raising and research have watched loved ones suffer and succumb to diseases like MS.
The failure of the medical establishment to solve mysteries like MS also prompts many patients to seek alternative remedies suggested by friends and relatives or found on the Internet. Many of these remedies are harmless, and some may actually be helpful, at least for a time. But when the remedies keep patients from trying the best that modern medicine can offer — or when they interact negatively with established remedies — the result can be a far more rapid downhill course than might otherwise have occurred.
The goal, then, for those considering alternative treatments is to make them complementary to, not competitive with, therapies that have passed muster in well-designed clinical trials.
“People have only one brain and one spinal cord, and what everyone with MS should be doing is optimizing treatment options every single day,” said Dr. Allen C. Bowling, a neurologist at the Rocky Mountain MS Center and author of “Complementary and Alternative Medicine and Multiple Sclerosis.” “Every patient should play the chips for which we have the best evidence. They should take advantage of what conventional medicine has to offer along with unconventional medicine,” as long as the latter does not interfere with the former.
Multiple sclerosis is an inflammatory autoimmune disease of the central nervous system in which the body’s own immune system attacks the myelin sheath that insulates nerves in the brain and spinal cord, resulting in irreversible damage to the axons that transmit nervous-system signals. About 400,000 people in the United States are affected, twice as many women as men.
MS is typically diagnosed between ages 20 and 40, but evidence indicates that it starts years before the first symptoms of weakness or disability appear. Even without a cure, many treatments are available — like drugs, physical and occupational therapy, exercise and rest — that can ease symptoms and delay the disease’s progression.
In most patients, the disease starts out, and may stay indefinitely, in a relapsing-remitting form that results in gradual progressive disability but is rarely life-threatening. In about 10 percent of patients, the disease is progressive from the outset and life expectancy is reduced.
The goal of therapy is to prevent relapses and the worsening of symptoms. Since symptoms can disappear on their own, large, long-term, scientifically controlled clinical trials are needed to determine what works and what only seems to work initially. Trials are also needed to uncover potentially serious side effects.
Such trials have identified half a dozen substances called immune modulators, five of which have been approved by the Food and Drug Administration as disease-modifying agents. These are Avonex, Betaseron, Copaxane, Novantrone and Rebif.
In her book “Multiple Sclerosis: An Essential Guide for the Newly Diagnosed,” Margaret Blackstone, a medical writer and MS patient, describes Avonex, Betaseron and Rebif as interferon-based treatments administered by injection that seek to calm an overactive immune system. Copaxane, also taken by injection, is an antigen that fools the body into thinking it is the protein in myelin. It is meant to protect the myelin from an immunological attack. Novantrone is an immunosuppressive cancer drug used to treat progressive MS.
A sixth drug, Tysabri, a monoclonal antibody that prevents immune cells from entering the brain, is given intravenously every four weeks. Tysabri was removed from the market in 2004 because of serious complications in three patients. It is now back in clinical trials and available through a special program to those who had found it to be the best treatment for their disease, but last week its makers posted a warning to doctors that it has been found to cause serious liver damage in some patients.
Therapy and Alternatives
Up to 20 percent of patients have a relatively mild form of MS and may not need drug treatment, but it is impossible to predict who they are. Dr. Bowling emphasized the importance of not waiting until neurological defects appear, since they cannot be reversed by any known therapy. He also said that therapies should be tailored to the nature of each patient’s disease and the known activity of the various drugs.
Ms. Blackstone states it is important for patients to recognize an impending relapse — common indicators are fatigue and “a heightened sense of vulnerability, as if the person can tell something bad is going to happen” — and not try to work through a relapse. “It’s better to rest” and “avoid engaging in strenuous activity,” she suggests.
If relapse symptoms warrant, corticosteroids can be used to speed recovery and possibly to delay or prevent another relapse. The other critically important aspect of therapy involves managing symptoms. Depending upon the stage and severity of the disease, symptoms may include fatigue, dizziness, vision changes, spasticity, weakness, tremor, numbness, balance problems, pain, depression, constipation and speech difficulties. In more advanced disease, sexual problems and incontinence are common.
Measures may be taken to reduce disability from these symptoms, like physical, occupational and speech therapy and psychotherapy; avoiding heat; getting adequate rest; and learning to listen to one’s limitations.
At one point or another, most MS patients also seek out, and often benefit from, complementary and alternative medicine, like acupuncture, dietary supplements, biofeedback, meditation, guided imagery, tai chi, cooling therapy, yoga, therapeutic touch and electromagnetic therapy. In his book, Dr. Bowling describes what is known about each of these possible adjuncts to medically established treatments, some of which can be counterproductive or negate the benefits of medication.
This is the first of two columns on multiple sclerosis. Next week: Could a special diet for MS patients be worth trying?