....treatment with AVONEX (Interferon beta-1a) promoted a statistically significant recovery of T1-black hole lesion volume by almost 24%....

Initial findings presented today at the 22nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) in Madrid, Spain showed that treatment with AVONEX (Interferon beta-1a) promoted a statistically significant recovery of T1-black hole lesion volume by almost 24% (p<0.05)>

The objective of this study was to evaluate the effect of AVONEX on global and focal disease as measured by multiple non-conventional and conventional MRI indices in a large sample of MS patients with either relapsing-remitting (RR) or secondary-progressive MS over 1 year. This study was an open label, single-blind, post-marketing, MRI observational study. 147 patients (131 with RRMS) were included with a mean pre-study disease duration of 11.1 years and followed for an average of 13.7 months. Patients received clinical and MRI examination at baseline and at the end of follow-up.

"This study represents one of the largest non-conventional MRI studies ever performed in patients with MS," said Dr. Robert Zivadinov, Associate Professor of Neurology and Director of the Buffalo Neuroimaging and Analysis Center, part of the Jacobs Neurological Institute, SUNY Buffalo, NY. He emphasized, "that the positive effect of AVONEX was particularly evident in patients with RRMS." This cohort represents a well-defined group of patients being on AVONEX monotherapy for a mean of 4.0 years before study entry. This study was funded by a grant from Biogen Idec.....

Biogen Idec: Additional Supplemental Application For Convenient Needle Locking System Filed With FDA:
"Biogen Idec Inc. announced that additional supplemental application was filed with the FDA for convenient needle locking system and change in room temperature storage.

The filing is to provide a new needle attachment, which will lock onto the syringe to make it easier for patients to know that the needle is firmly attached as well as a proposed change in the room temperature storage recommendations for AVONEX. AVONEX is the prescribed treatment for relapsing forms of MS....."

AVONEX, The Most Prescribed Multiple Sclerosis Therapy Worldwide, May Now Be Given with Smaller Needle:
"AVONEX(R) (Interferon beta 1a), the most prescribed multiple sclerosis (MS) therapy worldwide may now be administered with a needle that is 20 percent shorter and thinner than the currently approved needle. People living with MS and taking or considering AVONEX may speak with their healthcare provider to see if the smaller needle is appropriate for them..... "

Biogen Launches Smaller Needle For Avonex
The new needle is 20% shorter and thinner than the currently approved needle.

Biogen gets OK for prefilled Avonex syringes:
"Biogen says it expects the prefilled syringe to be available in August and replace the currently available form of Avonex."

TYSABRI - AVONEX: "Sometimes, the alligators in the closet bite"....MORE
By Dana Snyder-Grant
Thursday, June 22, 2006
I tried not to pay attention last year to the controversy about the MS drug, Tysabri. The drug, a therapy for relapsing MS and other auto-immune diseases, was taken off the market in February 2005 after three people who had been taking the medication in clinical trials, developed PMI, a rare and often fatal brain disease. Two of them died, including one person with MS. This month, the FDA agreed to let Tysabri return to the market with closer monitoring. The testimonials of people with MS who were unable to tolerate other disease-modifying medications and the rarity of the fatal occurrences together, swayed FDA regulators. I wonder why I hardly attended to this debate. I generally remain informed about MS. Perhaps fear played a role.

I've been taking a different MS medication, Avonex - an interferon that counteracts the MS auto-immune response - since September 1997, but the decision to do so had not been an easy one......."

AVONEX May Now Be Given With Smaller Needle....PLUS new auto injector on horizon

AVONEX(R) (Interferon beta 1a), the most prescribed MS therapy worldwide may now be administered with a needle that is 20 percent shorter and thinner than the currently approved needle. People living with MS and taking or considering AVONEX may speak with their healthcare provider to see if the smaller needle is appropriate for them.

Additionally, a supplemental application has been filed with the U.S. Food and Drug Administration (FDA) to provide a new needle attachment, which will lock onto the syringe to make it easier for patients to know that the needle is firmly attached as well as a proposed change in the room temperature storage recommendations for AVONEX. FDA action on this supplement is expected in the fall.

COPAXONE - AVONEX...Teva Neuroscience, Inc. (TEVA) News Release: COPAXONE Reduced Relapses And Stabilized Disability As Measured By Expanded Disability Status Scale, When Avonex Failed :

"Relapsing-remitting multiple sclerosis (RRMS) patients failing Avonex(R) (interferon beta-1a) therapy as defined in the study, achieved significant reductions in relapse rates and in Expanded Disability Status Scale (EDSS) scores, a measure of disability, upon switching to COPAXONE (glatiramer acetate injection). In a study published in the June issue of the European Journal of Neurology, COPAXONE was shown to reduce annual relapse rate by an additional 57 percent over Avonex, and that neurologic disability, as measured by the EDSS, did not worsen in 86 percent of patients.
'Our data demonstrated the benefits of COPAXONE in reducing relapse rate in patients who were not effectively treated or could not tolerate other immune modulating therapies,' reported Dr. Omar Khan, M.D., associate professor of neurology and director of experimental therapeutics/clinical research, Multiple Sclerosis Center, Wayne State University, and senior author of the study.
A series of 85 consecutive RRMS patients treated with Avonex(R) for at least 18 months who experienced suboptimal clinical efficacy (at least one relapse in the previous year, n=62) or persistent intolerable toxicity (elevated liver function tests, low white blood cell counts, or post-injection fever, weakness, or fatigue for more than 24 hours after every injection, n=23), were switched to COPAXONE in this open-label study and followed prospectively for an additional 36 to 42 months (average 37.5 months). While on COPAXONE( therapy, patients were seen every six months for neurological examinations, including EDSS scores.
Annualized relapse rate for the entire patient group after switching to COPAXONE(R) (glatiramer acetate injection) was reduced by 57 percent from 1.23 on Avonex(R) to 0.53 (p=0.0001). In the subset of patients who switched to COPAXONE because of insufficient efficacy on Avonex (n=62), the reduction was even more significant (61 percent), from 1.32 to 0.52 (p=0.0001). Patients who switched to COPAXONE because of persistent toxicity on Avonex(R) (n=23), experienced an additional 23 percent reduction which did not reach statistical significance.
In all patients, the average EDSS scores, as a measure of neurological disability, significantly improved during the more than three years of COPAXONE(R) therapy, decreasing from 3.50 to 3.08 (p=0.0001). Improved or stable EDSS scores occurred in 86 percent of patients.
'We recognize the limitations of our study, such as the open-label design and lack of prospective follow-up in patients while receiving IFN beta-1a,' stated Dr. Khan. 'However, our results corroborated another larger prospective open-label study by Howard Zwibel, M.D., Medical Director of Health South Doctors' Hospital Multiple Sclerosis Center, which demonstrated reductions in relapse rates in patients switched from Betaseron to COPAXONE, and suggested that clinical observations including relapse rates, patient tolerability, and toxicities assessed by serum laboratory parameters are valuable criteria for determining when a switch in therapy is warranted.,,,,'"

JOB OPENING: AVONEX MARKETING TEAM PRODUCT MANAGER
Location: Cambridge, Massachusetts
Posted on: 3:08 PM, Tuesday, May 23, 2006
Position type: Full time
Job Code: 324197
Required education:
Area(s) of expertise desired:

Description
AVONEX MARKETING TEAM PRODUCT MANAGER: This position will drive development and implementation of effective patient marketing strategies and tactics specific to patient acquisition for the leading product in the multiple sclerosis market. This position will be accountable for the following activities:
·Development of patient promotional material
·Execution of patient acquisition plan
·Cross-functional coordination and communication across channels

Requirements
The qualified candidate must have demonstrated abilities to lead cross-functional teams, prioritize and manage multiple projects, proactively define direct to patient (DTP) opportunities, and effectively influence and communicate with internal and external partners. Three to five years of sales or marketing experience required.
Other qualifications include:
·Strong communication skills
·Strong analytical and organizational skills
·Strong interpersonal skills

HealthTalk - MS - Treating MS: The Disease and Its Symptoms: "Hear how medications are improving, both to slow long-term progression of MS and manage day-to-day symptoms."
When: June 22, 2006 - 8:30 p.m. Eastern (5:30 p.m. Pacific)
Where: On the phone - On the Internet
George Hutton, M.D. - George Hutton, M.D.
[The site is owned by a Biogen/Avonex - it is very good]

MORE: Reuters.com: "The CEO of the U.S. maker of multiple sclerosis treatments said that he saw no sense in a deal...because of their important MS products there would be huge competition issues in Europe and the U.S.'"

CLICK FOR MORE INFORMATION

MORE=Entrez PubMed
: "CONCLUSIONS: Beta interferon therapy in the first trimester of pregnancy appears to be associated with an increased risk for fetal loss and low birth weight."

MORE-Entrez PubMed

MORE-Entrez PubMed

CLICK HERE TO GO DIRECTLY TO THE "AVONEX" HOME PAGE

Neutralizing Antibodies can significantly decrease the effectiveness of IFN-b in the treatment of MS

Three studies published in Neurology which included more than 1200 patients, confirm that the three interferon preparations used to treat relapsing-remitting multiple sclerosis (MS) vary in their rate of production of neutralizing antibodies (NAbs).

Further, there is agreement that NAbs reduce or eliminate the biologic activity and clinical efficacy of the interferon-beta (IFN-b) therapies.

Once-weekly Avonex® (interferon beta-1a IM) was shown to be significantly less likely to induce the development of NAbs than the other two available interferon therapies (Rebif® and Betaseron®). Since NAbs reduce or eliminate the clinical benefits of the interferons, these studies highlight a concern for MS patients, neurologists and those who pay for these medications.

For the many Canadians living with MS, and currently being treated with IFN-b therapy, this is important data.

"MS is a chronic disease, and patients need to have the confidence that their therapy will retain its efficacy throughout the course of treatment, which is often for many years," commented Dr. Stanley Hashimoto, neurologist and former medical director of the University of British Columbia MS Clinic, Vancouver, Clinical Director of the UBC MS Clinic, Vancouver, British Columbia. "These studies confirm that in MS, high titre and persistent NAbs are very important in eliminating the efficacy of the therapeutic agent. It is important that we have available a less immunogenic option such as Avonex®."

While each of the studies showed slightly different rates of NAbs, Avonex® (interferon beta-1a IM) consistently demonstrated the lowest rates as compared to the other IFNb therapies. For example, in the first study the Danish Multiple Sclerosis Study group (Neurology 2005;65:33-39) concluded, "Unlike previous findings reported in the literature we did not find any difference in the proportion of patients treated with [Betaseron®] and [Rebif®] who became NAb-positive, but could confirm that Avonex® is much less immunogenic."

In the second study, Kappos and associates (Neurology 2005;65:40-47) analyzed 395 patients over four years in a controlled trial, and clearly demonstrated the loss of efficacy in terms of relapse rate reduction and disability progression over a significant number of years. It can be assumed from this research, that persisting NAbs beyond the four years will continue to suppress the therapeutic activity of the interferons. This was also echoed by Drs. Giovannoni and Goodman in their Editorial (Neurology 2005;65:6-8).

The third study, authored by Dr. Gordon Francis et al. (Neurology 2005;65:48-55), concluded that, "Neutralizing antibody development in IFN-b-treated patients is correlated with reduced efficacy and is a potential cause for renewed (MS) disease activity."

"Many patients being treated for MS are not getting the efficacy they deserve because of the neutralizing effect of NAbs," said Dr. Hashimoto "This is not to mention the fact that our healthcare system is paying for these drugs without realizing the potential negative effects of neutralizing antibodies."

The Danish Multiple Sclerosis study group agreed that the presence of NAbs decrease or eliminate efficacy of the interferons. They recommended that to avoid these negative consequences, all patients on the therapies should be tested at six-month intervals for two years when it becomes less likely the new positivity will develop. Routine testing will assure patients that they are self-injecting their medication and getting benefit from it.

With recent concerns about existing and future MS treatments, patients and physicians are reassessing currently available therapies, like the interferons. As a result, it is more important than ever to re-evaluate which therapy will provide efficacy over the long-term, including minimizing the formation of NAbs


docguide.com

"Low scores on the Expanded Disability Status Scale (EDSS) at the beginning of treatment with interferon beta-1a (Avonex) in multiple sclerosis patients is associated with a longer duration of treatment, according to research presented here on September 29th at the 21st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).....In addition, said the investigators, treatment failure is mostly due to progression of disability rather than persistence of a high relapse rate....."We found that the discontinuation of treatment is more frequent in patients with baseline higher EDSS scores but there is no significant difference in terms of disability progression with subjects with low baseline EDSS and subjects with high EDSS." MORE

"Treatment of multiple sclerosis with interferon beta-1a (Avonex) is equally efficacious in men and women, with similar safety profiles in both genders, researchers reported here on September 29th at the 21st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
"MORE

OBJECTIVES: The aim of this study was to identify clinical, magnetic resonance imaging (MRI) and biological markers predictive of long-term clinical response to interferon beta (IFN beta) therapy in patients with relapsing-remitting multiple sclerosis (RRMS).METHODS: Sixty-eight patients treated with IFN beta were followed over a 6-year period. Relapse rate and disability progression were evaluated throughout the study. We considered suboptimal clinical response to be either the presence of sustained disability progression, or more than two relapses. Baseline and 12-month demographic, clinical and MRI findings, as well as the development of neutralizing antibodies (NAbs) against IFN beta during the first year of therapy were analyzed as predictors of long-term clinical outcome..CONCLUSIONS: Variables assessable within the first year of treatment significantly influence relapse rate and disability progression in patients with RRMS treated with IFN beta. These findings may help clinicians to make decisions regarding therapy regimen over time, and highlight the need for a prognostic algorithm.Entrez PubMed

Women with MS who choose to go on interferon beta drugs are advised to stop treatment if they decide to try to become pregnant. This advice is based on data from animal studies that suggest these drugs may increase the risk of miscarriage. However, since animal studies are imperfect substitutes for human experience, a group of doctors decided to pore through pregnancy data collected during eight IFN-b trials to determine whether being on the drug did have an impact on pregnancy outcome. They found that IFN-b did appear to slightly increase the risk of miscarriage but not to a significant degree. "Reviewing the data from each of the trials, the team found 31 women who conceived while on the drug or within two weeks of ending treatment, and who chose not to terminate their pregnancy. Of these, 22 gave birth to live infants (although one was born prematurely and another had a birth defect). The other 9 miscarried or experienced fetal death (loss of pregnancy after 20 weeks). This on-treatment pregnancy loss rate is higher than the average estimated rate in the general population, but not significantly so. Also identified in the study data were 22 women who had been on IFN-b but stopped two or more weeks prior to becoming pregnant. Each of these women delivered live infants, although one was born prematurely and another had a congenital abnormality.
Overall, these data indicate that IFN-beta treatment does not dramatically increase the rate of lost pregnancies and that the majority of women who conceive while on treatment go on to deliver healthy babies. However, because of the slightly increased risk of pregnancy loss, women who are planning to become pregnant are still advised to end treatment at least two weeks before conceiving."...Click to read ...Entrez PubMed

Click to read... The study, which is still ongoing, is labeled Quality Assessment in MS Therapy, or QUASIMS. "The goal of this study was to compare the efficacy of interferon-beta products in relapsing MS in different clinical settings throughout the world," Limmoth and his fellow investigators wrote. Patients were included in the study if they had been taking one of four interferon betas uninterrupted for at least two years. That included 30 micrograms (mcg) of Avonex (interferon beta-1a) once per week, 250 mcg of Betaseron (interferon beta-1b) once every other day, or two different doses of Rebif (interferon beta-1a): 22 mcg or 44 mcg three times per week.

"Efficacy was similar among patients treated with the four different interferon-beta preparations in different countries," the researchers wrote. "Switching between different interferon preparations did not appear to provide additional benefits."

MS Active Source
800-456-2255

www.avonex.com
www.msactivesource.com
www.healthtalk.com

LINKAvonex is a form of interferon beta. Interferons are proteins naturally produced by the body to help fight viral infections and regulate the immune system.

Avonex is made up of the same arrangement of amino acids, the building blocks of proteins, as the interferon beta produced by the body.

MS is thought to be a disease in which the body's immune system responds against myelin, the insulation surrounding nerve fibers, causing its deterioration.

It is believed that Avonex regulates the body's immune response to decrease the attack against myelin.

With Avonex, more medicine gets into the bloodstream and stays in the body longer because injections are given into the muscle. This is part of the reason that Avonex injections are only administered once-a-week.

Other treatments for MS are given by subcutaneous injection - under the skin - and must be taken every day or every other day.

Unlike injections given under the skin, injections into the muscle rarely produce uncomfortable and unsightly injection site reactions.

Most people can adjust well to treatment with Avonex. But as with all MS treatments, side effects can occur.
The most common side effects associated with Avonex treatment are flu-like symptoms, muscle ache, fever, and chills.

Other common side effects seen, but not statistically different between Avonex and control groups in clinical studies were headache (Avonex: 67%, placebo: 57%), pain (Avonex: 24%, placebo: 20%), and asthenia (weakness) (Avonex: 21%, placebo 13%).

These side effects usually go away within a day after the injection.

There are several ways to manage these flu-like symptoms, including taking an analgesic such as Tylenol.

Avonex should be used with caution in people with depression and in people with seizure disorders, and should not be be used by pregnant women.

People with cardiac disease should be closely monitored. Routine periodic blood chemistry and hematology tests are recommended during treatment, as well.

CLICK HERE TO GO TO AVONEX HOME PAGE

...Interaction with Avonex may be fatal

LINK - The Boston Globe

Elan Corp. and Biogen Idec Inc.'s multiple sclerosis drug Tysabri may have killed patients because interaction with another Biogen product, Avonex, led to a buildup and overdose of the medicine, an NCB Stockbrokers analyst said.

An interaction of Tysabri, recalled Feb. 28, and Avonex, an older MS drug sold by Biogen ''essentially leads to almost double the intended Tysabri concentration after only 20 weeks," NCB analyst Orla Hartford said yesterday in a note to investors. ''Patients on Tysabri alone did not accumulate the drug."

The effect Avonex has on Tysabri will likely ''form a central part of the case made to the FDA for Tysabri's relaunch," she said. Hartford, who analyzed data submitted to the US Food and Drug Administration during the approval process, expects the treatment to be reintroduced in 2006.

''Elan's continuing with the review, which is on track, and will comment when it has been completed," said Elizabeth Headon, a spokeswoman for Elan at Murray Consultants.
Tysabri was withdrawn after being linked to progressive multifocal leukoencephalopathy, a rare neurological disease, in two patients, both of whom were taking a combination of the two drugs. Elan and Biogen Idec are reviewing medical records of patients who have taken the drug. The companies will meet with the FDA to determine whether the drug can be sold again.
''The efficacy of Tysabri in treating multiple sclerosis is undeniable and we continue to believe that Tysabri will return to the market as a significant therapy," Hartford said.
Shares of Biogen rose 56 cents yesterday to close at $34.65 on the Nasdaq Stock Market.
Tysabri is the cornerstone of Elan chief executive Kelly Martin's plan to reach profitability and repay debt due in 2008 and 2011. He said in May he's confident the drug will return to the market.

Hartford said that over a sustained period of time, Tysabri accumulated in the system partially because the body is less able to process it, which leads to an ''overdosing," she said.
The Tysabri accumulation may have led to a suppressed local immune system in the brain and may have been a key predisposing factor in the two cases of PML seen in combination therapy, Hartford said.

A third patient, identified in March, wasn't taking Avonex, but was on azathioprine, another immunosuppressive drug. Other possible cases have been reported to the FDA, but they haven't been confirmed.

Multiple Sclerosis Society of London Website - linkMitoxantrone is a potent immunosuppressant used in the treatment of some forms of cancer. It is licensed in the US for the treatment of worsening relapsing remitting MS and relapsing progressive MS. This study investigated the effectiveness of mitoxantrone as a "rescue therapy" for people taking beta interferon who continued to experience disabling relapses or significant disability progression.

Ten people who experienced more than three relapses a month and had rapid disability progression took part in the study. Neurological assessments, MRI scans and blood tests, both to monitor ongoing inflammation, were completed initially, every three months and within three days of a relapse. After six months receiving just beta interferon participants received three infusions of mitoxantrone into the vein, in combination with steroids, shown to shorten the recovery time after a relapse, once monthly. After an additional six months of just beta interferon therapy people who did not show a benefit from the first combination therapy again received intravenous infusions of mitoxantrone, in addition to beta interferon therapy, at the rate of once every three months. All participants were monitored for the following 15-18 months.

During the first three months of mitoxantrone treatment none of the participants experienced any relapses and disability levels stabilised. The amount of inflammation present also significantly decreased compared to levels present during beta interferon therapy alone. During the following six months of just beta interferon treatment the relapse rate remained significantly reduced and inflammation levels remained low. Disability levels for seven of the 10 participants remained stable after the initial mitoxantrone treatment. The remaining three participants received additional mitoxantrone, as described. During further mitoxantrone treatment these participants experienced no new relapses and their disability stabilised. Overall, mitoxantrone was well tolerated with a low number of adverse events reported.

In conclusion, mitoxantrone administered concurrently with beta interferon was effective in significantly reducing both the relapse rate and levels of inflammation in people with MS. It also effectively stabilised disability progression in people with rapidly progressive disease. Positive effects were still detectable after 15 months. The authors highlight that further studies of agents for rapidly progressing MS are warranted.

LINK PubMed
"These data showed that the combination of CTX plus IFN beta halted the progression of disease in active and deteriorating MS patients suggesting the necessity of RCTs to test the efficacy of this combination therapy in active RRMS patients or in patients who experienced treatment failure in response to disease modifying drugs (DMDs)."

The Lancet Neurology...LINK TO ARTICLEInterferon beta was the first therapy to be approved for the treatment of relapsing-remitting multiple sclerosis (MS) more than 10 years ago. Interferon beta reduces relapse rates and disease burden and activity, and it may have beneficial effects on the progression of long-term disease disability. The occurrence of neutralising interferon-beta antibodies has been postulated as a possible cause of the failure of interferon beta in some patients with MS. Here we discuss the basic mechanisms that may account for the generation of an interferon-beta antibody response and its biological implications. We review the evidence for neutralising antibodies as a consequence of interferon-beta treatment, and discuss the implications for the treatment of MS. Strategies to assess and manage the long-term impact of neutralising antibodies will be outlined.

LINK

WebMD: LINK TO COMPLETE STORY"Patients taking the multiple sclerosis (MS) drug Avonex should be watched for possible liver problems, says the drug's maker."

The New York Times: Published: March 17, 2005"Biogen Idec's multiple sclerosis drug Avonex might cause severe liver damage in rare cases, the company and the Food and Drug Administration said yesterday.The warning was another blow, though probably only a glancing one, to Biogen, which is already reeling from the halt in sales of its other multiple sclerosis drug, Tysabri, which was linked to a rare brain infection.

In a related development, GlaxoSmithKline said yesterday that the F.D.A. had ordered it to halt a trial of its multiple sclerosis drug, which works in a similar way as Tysabri.

A Glaxo spokesman said the company understood that a halt was made as a precaution in trials of all drugs in the same class as Tysabri. A spokeswoman for the F.D.A. said the agency could not comment because of confidentiality about clinical trials.

In a letter that was posted on the F.D.A. Web site, Biogen said that severe liver injury, including liver failure, "has been reported rarely in patients taking Avonex." It said doctors should especially consider the risk when Avonex is used along with other drugs that can cause liver damage, or by patients who drink alcohol.

Amy Ryan, a spokeswoman for Biogen, which is based in Cambridge, Mass., said there had been only a handful of cases among the 130,000 patients using Avonex, which has been on the market since 1996. She said a "minor update" was being made to the drug's label, upgrading liver damage from a "precaution" to a stronger "warning."

It is not uncommon to find new side effects of drugs as they are more widely used. The label of Rebif, a drug very similar to Avonex that is made by Serono, already comes with a warning about liver problems.

Still, with Tysabri off the market at least temporarily, Biogen will become more dependent for growth on Avonex, its biggest product, which had sales of $1.4 billion last year. Its shares fell 88 cents, to $37.19.

Both Ms. Ryan and Kathleen Quinn, a spokeswoman for the F.D.A., said that there was no connection between the Avonex warning and the Tysabri withdrawal, and that the timing was coincidental.

Biogen and Elan, its partner on Tysabri, suspended sales of that drug on Feb. 28 after two patients in clinical trials came down with a rare viral brain infection, progressive multifocal leukoencephalopathy. The two patients, one of whom died, had been taking both Tysabri and Avonex for more than two years in a clinical trial.

Tysabri, which was approved in November, works by stopping certain infection-fighting white blood cells from leaving the bloodstream to enter the brain. That helps stop the cells from attacking nerve cell insulation in people with multiple sclerosis but also might leave them more vulnerable to brain infections, some specialists say.

Glaxo was in Phase 2, the middle stage of testing, of its drug, 683699, which blocks the same protein as Tysabri. The drugs are different chemically and the Glaxo drug was not being tested in combination with Avonex.

Glaxo's drug, being developed with Tanabe Seiyaku of Japan, appears to be the most advanced in trials of drugs that work by blocking that protein, called alpha 4 integrin. Antisense Therapeutics, an Australian company, said last week that it was halting an early Phase 2 trial of its alpha 4 integrin drug, ATL1102, to assess the situation.

Pharmaprojects, a British database that tracks pharmaceutical development, said in a news release yesterday that 12 such drugs were in development, mostly for asthma; 5 are being developed for multiple sclerosis.

Meanwhile, Biogen's chief executive, James C. Mullen, said yesterday that there were "no other indications" of the viral infection beyond the first two patients. In a Webcast presentation at the SG Cowen Health Care Conference in Boston, he said that as time elapsed, "the absence of negative news one can view as positive."

Still, he said, it would take weeks to check the medical records of all the patients in Tysabri trials and to give them new MRI scans and other tests.

He did not say when, or if, he thought the drug could return to the market. But he said that if no more cases arose, the drug might be able to return without extensive new clinical trials. Biogen for now is keeping its sales force intact and continuing to manufacture Tysabri, though at a slower rate than before, he said."