[Fwd: Fwd: FDA Approves Tysabri's Return to Market]

[Guest guest]

This is good news Darlene.

Bill

DRiha15233@... wrote: From: DRiha15233@...Date: Tue, 6 Jun 2006 17:29:04 EDTSubject: Fwd: FDA Approves Tysabri's Return to MarketTo: cheri.furgason@... To: "'Kraus'" Subject: FDA Approves Tysabri's Return to MarketDate: Tue, 6 Jun 2006 08:33:10 -0400 You have received this email because you have previously been in contact with the National MS Society-Indiana State Chapter requesting information. If you wish to be removed from this confidential list, please reply back to this email requesting removal. ------------------------------------------------------------------------------------------------------- June 5,

2006 FDA APPROVES Tysabri’s Return To Market For Relapsing MS -- Company Hopes to Make Drug Available in July The U.S. Food and Drug Administration has approved the

return to market of Tysabri® (natalizumab), produced by Biogen Idec and Elan Pharmaceuticals, to delay the accumulation of physical disability and reduce the frequency of relapses (clinical exacerbations) in those with relapsing multiple sclerosis. The approval is based on positive results from two clinical trials showing that Tysabri significantly reduced the risk of sustained progression of disability and the rate of clinical relapse in those with relapsing MS. The approval hinges on a mandatory registration program for patients and prescribing physicians to minimize the risks that patients will develop PML (progressive multifocal leukoencephalopathy), caused by a common virus called the JC virus. Three people who had

been in clinical trials involving Tysabri developed PML, two of whom died. The drug, which is taken by monthly IV infusion, will be dispensed at registered infusion centers across the country. Tysabri is generally recommended for patients who have had inadequate response to, or are unable to tolerate, other approved MS therapies (such as Copaxone, ® Betaseron, ® Avonex, ® Rebif® and

Novantrone®). It is approved as a monotherapy, not to be combined with other immune system-modifying agents, and is not recommended for individuals who have compromised (weakened) immune systems. According to company sources, there will be a delay between the time of FDA approval and the time when Tysabri is available to patients. Several weeks are needed to develop training materials and to finalize the patient data collection system. The companies hope to commercially launch Tysabri, or make it available for use, in July 2006. Individual patients may experience additional delays, depending on the availability of a nearby registered infusion site

and any health insurance coverage issues. As part of its approval, the companies have agreed to conduct a post-marketing study that will follow some 5,000 patients prescribed Tysabri for five years to evaluate the long-term safety of the drug in the clinical practice setting. “It’s important that people with relapsing MS now have a new treatment option,”

said Dr. R. Richert, National MS Society Vice President of Research and Clinical Programs. “We believe that the mandatory patient registry and post-marketing observational study will help clarify the potential risks and benefits of this new therapy for people with MS,” he added. Key aspects of the approval include: ·

Tysabri is approved to delay the accumulation of physical disability and reduce the frequency of clinical exacerbations (flare-ups or relapses) in patients diagnosed with relapsing MS; · Tysabri will only be available under a restricted distribution program called TOUCH, and prescribing physicians and patients must enroll in this mandatory registry program; · Tysabri can be given only at registered infusion centers where the medical personnel have been trained in its proper use and in the risks of PML; · Tysabri should be given as a monotherapy, meaning it should not be combined with other medications that alter immune function; · Tysabri is generally recommended for patients who have had inadequate response to, or are unable to tolerate, other approved MS therapies; · Tysabri is not recommended for patients who have compromised (weakened) immune systems or who are taking other drugs that suppress or modulate the immune system, with the exception of periodic steroids to treat relapses; · Prescribing information carries a “Black Box Warning” to highlight the increased risk of PML and the importance of monitoring patients for any new signs or symptoms that may be suggestive of PML. · An MRI scan must be obtained prior to starting treatment with Tysabri; · Prior to each infusion, the patient and infusion nurse complete a checklist to screen for symptoms suggestive of PML; and · Patients on Tysabri are to be evaluated by the prescribing physician 3 and 6 months after the first infusion and every 6 months thereafter, and their status will be reported to Biogen Idec. Additional details about how and when Tysabri will become available for infusion will be forthcoming. ü For information about the FDA approval, go to the FDA’s Web site at: http://www.fda.gov/cder/drug/infopage/natalizumab/default.htm

ü For Questions & Answers and other updated information from the National MS Society, visit our Web site at http://www.nationalmssociety.org/tysabri.asp. ü For further information about the availability of Tysabri,

individuals may call Biogen Idec’s MS Active Source information line at: 1-, or go to the Biogen Idec Tysabri information site at http://www.biogenidec.com. ----------------------------------------------------------------------------------------------------------- Frequently asked Questions and their Answers concerning FDA APPROVAL OF tYSABRI About Tysabri and its Availability Q. What is Tysabri (pronounced Tie-SAB-bree) and how does it work? A. Tysabri (whose scientific name is natalizumab, pronounced:

nat-tal-IZ-zue-mab) is a laboratory-produced monoclonal antibody. It was formerly called Antegren. It had been approved for marketing by the U.S. FDA for relapsing forms of MS, based on data from the first year of two, 2-year clinical trials. Tysabri is designed to hamper the movement of potentially damaging immune cells from the bloodstream, across the “blood-brain barrier,” and into the brain and spinal cord. The drug inhibits this movement by attaching to alpha 4-integrin, a protein on the surface of immune T-cells that normally enables them to adhere to and pass through the blood-brain barrier. Because of this mode of action, Tysabri is called a selective adhesion molecule

inhibitor (or “SAM”). This approach was initially studied in animal models, including studies supported by the National MS Society, which showed that monoclonal antibodies could block such immune cell movement and ameliorate disease. These animal studies led to the successful human studies. Q. Who should take Tysabri? A. Tysabri has been approved for persons with relapsing forms of multiple sclerosis. Relapsing MS means that individuals experience flare-ups of symptoms in the form of periodic attacks, which then subside with total or partial recovery. Relapsing forms of MS may include those with relapsing-remitting MS, progressive-relapsing MS, and those with secondary-progressive MS who experience relapses. According to the FDA approval,

Tysabri is generally recommended for patients who have had inadequate response to, or are unable to tolerate, other approved MS therapies. The question of who should take Tysabri is something that can only be answered through discussions between an individual and his or her neurologist. Q. In terms of who can be prescribed Tysabri, who determines what constitutes an “inadequate response” to currently approved MS therapies? A. The FDA’s approval of Tysabri does not specifically define

“inadequate response,” nor does it define what constitutes an inability to tolerate alternate MS therapies. Therefore, the decision about whether to take or switch to Tysabri must be made after careful consideration by a person with MS together with his or her personal physician. Q. How long will I have to wait before I can take Tysabri? A. According to company sources, there will be a delay between the time of FDA approval and the time when Tysabri is available to patients. Several weeks are needed to

develop training materials and to finalize the patient data collection system. The companies hope to commercially launch Tysabri, or make it available for use, in July 2006. Individual patients may experience additional delays, depending on the availability of a nearby registered infusion site and any health insurance coverage issues. Q. How much will Tysabri cost? A. The price of Tysabri and any related tests or risk management procedures has not yet been released. Prior to its withdrawal from the market in

2005, the wholesale cost per vial was announced at $1,808 (taken every 4 weeks, the yearly wholesale cost was $23,504). Q. Will my insurance cover the cost of Tysabri? A. Since Tysabri’s approval is new, many health plans will probably not be able to reach any conclusions about coverage yet. Sometimes there is a lag time before a new drug is included as part of a health plan’s formulary. Prior authorization will probably be necessary for most health plans. More information will be forthcoming when

details become available. Q. Does Medicare cover the use of Tysabri? A. Because Tysabri is an infusion given at a medical facility, it will probably be covered by Medicare Part B. Q. How is Tysabri taken? A. Tysabri is given via monthly intravenous infusion at a medical facility. As part of the risk management plan, Tysabri will be available only at registered infusion centers. The companies estimate that there will eventually be 2,000 such centers in the United States . These may include doctor’s offices, hospital clinics and stand-alone clinics. Q. How long does an infusion take? A. The actual infusion takes about one hour. The overall visit will take longer than that because of the risk management discussion and paperwork that will need to be taken care of at the infusion site. Q. Are infusions painful? A. A person

getting an intravenous infusion will probably feel a sharp pain or some discomfort when the needle penetrates the skin and vein, but then the discomfort should subside as the infusion proceeds. There may also be discomfort when the infusion needle is removed and the site may or may not feel sore for a day or so. Q. Should I switch from the therapy I’m taking now? A. This question can only be answered through discussions between an individual and his or her neurologist. The discussion

should focus on how well the individual is doing on his or her current therapy and what is currently understood about the potential risks and benefits of Tysabri. Q. I have relapsing MS and have never tried any of the disease-modifying therapies. Will I be able to use Tysabri? A. The FDA recommends that Tysabri be used only in persons who have had inadequate response to other approved MS therapies, or who are unable to tolerate other approved MS therapies. This is a question you should discuss with a neurologist

who is knowledgeable about MS and familiar with your condition and personal circumstances. Q. Can I switch to Tysabri if I’m on another MS drug right now? A. Possibly. This is a matter that should be discussed with your neurologist. The prescribing information states that Tysabri should not be given to patients whose immune systems are compromised, or weakened. There will likely be a period of time between the end of your current therapy and the beginning of Tysabri. The length of time may vary depending on the type of therapy you are currently

on and the period necessary to “wash out” the current drug from your system. If a person is currently using an approved MS therapy such as Copaxone or interferon beta and is being switched to Tysabri, the “wash out” period would probably be a few weeks before beginning Tysabri infusions. If a person has recently been prescribed Novantrone, Cytoxan, Imuran or other strong immune-suppressing drug, the “wash out” period would be longer before beginning Tysabri. This should be discussed with your neurologist. The FDA-approved prescribing information does not provide specific recommendations for “wash-out” or waiting periods before beginning treatment with Tysabri.

However, for the post-marketing study involving persons who had been enrolled in the original phase 3 studies of Tysabri (AFFIRM and SENTINEL trials), the FDA recommends that anyone who has been taking an immune-modifying MS drug (such as Copaxone, Betaseron, Avonex, or Rebif) should not begin Tysabri for two weeks after the last dose, and that anyone who has been taking an immune-suppressing drug (such as Novantrone, Cytoxan or Imuran) should not begin Tysabri for three to six months after the last dose. Q. How effective is Tysabri? A. In a two-year clinical trial of two years’ duration (the AFFIRM study) of Tysabri alone, 942 individuals received either Tysabri or inactive placebo for more than two years. The treated group experienced a 42% reduced risk of progression of disability, a 68% reduction of clinical relapses, and an 83% reduction in the development of new or newly enlarging MRI-detected brain lesions. Tysabri also reduced the mean number of enhancing (active) MRI lesions by 92% after the first and second year. These results were described in a published paper (The New England Journal of Medicine 2006;354:899-910). A second two-year trial of two years’ duration (the SENTINEL study) involved 1171 individuals with relapsing MS who were on Avonex but had experienced at least one relapse during the previous 12 months. All participants continued on Avonex, in combination with either Tysabri or inactive placebo given by intravenous infusions every four weeks for up to 116 weeks. After one year, participants who had Tysabri added to Avonex experienced a 54 percent reduction in the rate of clinical relapses compared to those on placebo and Avonex, which was also maintained at two years with a 55 percent reduction. This combination therapy resulted in a 24 percent decrease in the risk of sustained disability progression. MRI scans showed an 83-percent reduction in the Tysabri plus Avonex group in enlarging MRI lesions, and an 89-percent reduction in lesions showing active inflammation. Results of this study were described in a published paper (The New England Journal of Medicine 2006;354:911-923). Two cases of PML, one of which was fatal, were diagnosed in those on combination therapy. Q. What is meant by the statement that Tysabri should not be taken by patients who have compromised immune systems or who are taking other immunosuppressive or immunomodulatory agents?A. This means that Tysabri would not be used in patients whose immune systems are weak, such as people who have MS and leukemia or lymphoma, or who are taking immune-suppressing drugs or other MS drugs such as interferons (Avonex, Betaseron, Rebif), Copaxone or Novantrone. Other drugs sometimes taken by people with MS which may weaken their immune systems include Cytoxan or Imuran, or monthly intravenous steroids. There is no warning against the use of periodic steroids to treat relapses in people taking Tysabri; however, the chronic use of “pulse” or monthly steroids would possibly weaken the immune system and therefore should probably be avoided. Q. Is Tysabri better than the other available MS therapies?A. Tysabri has not been compared head-to-head against any other approved MS drug, and that is

the only way to truly compare the effectiveness of the MS drugs. However, generally clinicians agree that the immunomodulatory drugs approved for use in MS reduce the rate of relapses by about one-third. By contrast, after two years Tysabri reduced the rate of relapses by about two-thirds as compared to placebo. The investigators also reported that Tysabri reduced the risk of sustained progression of disability over those two years. These is some evidence that other approved MS drugs also slow disease progression. It is important to note that since MS is such a diverse disease, there is no “one size fits all” treatment strategy. Any decision about whether to take any of the

disease-modifying therapies should be made after careful discussion between a patient and his or her physician of its potential risks and benefits. The National MS Society does recommend that upon diagnosis individuals with relapsing MS consider early proactive treatment with one of the FDA-approved therapies for MS that have been shown to impact the underlying disease course. Q. Where can I call to get more information about Tysabri? ü For information about the FDA approval, go to the FDA’s Web site at: http://www.fda.gov/cder/drug/infopage/natalizumab/default.htm ü For a summary of the approval announcement and other updated information from the National MS Society, visit our Web site at http://www.nationalmssociety.org/tysabri ü For further information about the availability of Tysabri, individuals may call Biogen Idec’s MS Active Source information line at: 1-, or go to the Biogen Idec Tysabri information site at http://www.biogenidec.com. Safety Concerns About Tysabri Q. What is the primary safety concern regarding the use of Tysabri? A. A primary

safety issue is the fact that three people who had been in clinical trials involving Tysabri developed a rare disease called PML (progressive multifocal leukoencephalopathy), caused by a common virus called the JC virus. Two of them died, including one person with MS. Q. If I take Tysabri, what are the risks that I will get PML?A. No one knows the true risk of getting

PML outside of the clinical trials of people taking Tysabri. According to a study published in The New England Journal of Medicine (The New England Journal of Medicine 2006;354:924-33), the risk in the clinical trials population, who had taken an average of 17.9 doses of Tysabri, is one in one thousand. Go to summary of these findings here There is not enough known about the true risk of getting PML in people who may use Tysabri. For these and other reasons, Biogen Idec and Elan have developed procedures for the careful tracking of adverse events and has established a large observational study to help evaluate the long-term safety of Tysabri. Q. Will I be safe if I take Tysabri alone, without any other drugs that alter the immune system? A. No one knows. During the March 2006 advisory committee meeting held by the FDA about Tysabri, FDA representatives stated that the risk of PML in those who took Tysabri alone versus those who took Tysabri in combination with Avonex is still unclear. That means that at this time there is insufficient data to determine whether PML was caused by taking Tysabri in combination with other immune-modulating drugs, or whether PML can arise in those taking

Tysabri alone. Q. Are there any tests that can be done to know in advance whether you are at risk for developing PML? A. No. Q. Are there any tests that can

be done to know if you are developing PML? A. Yes. If a person begins to show persistent signs of new or worsening neurological symptoms, they would likely be taken off Tysabri. Then their doctor would likely begin tests of the blood and spinal fluid as well as obtain an MRI scan of the brain to help determine whether the JC virus that causes PML is present and active. Q. What are the signs of PML that a person using Tysabri should look out for? A. All of

this will be clearly explained in patient information that will be supplied to individuals before they begin taking Tysabri. Patients will be cautioned to inform their prescribing physicians and/or infusion nurse if they experience any new or worsening neurological symptoms. These might include any changes in thinking, eyesight, balance, strength and other symptoms. Q. What is the treatment for PML? A. There is at present no drug that has been proven to fight the JC virus. Therefore, treatment consists of reconstituting the immune system by

withdrawing any immune-suppressing therapies. Q. Are there risks of getting other serious infections if I take Tysabri? A. The clinical trials of Tysabri in MS did not reveal significant differences in serious infections between those on active treatment versus those on inactive placebo. However, the risks of longer-term exposure to Tysabri are currently unknown. FDA scientists reviewing safety data pointed out that Tysabri’s mode of action inhibits the recruitment of immune cells to sites of infection, making it possible that risks of serious or opportunistic infection may exist. According to the drug’s labeling, the immune system effects of Tysabri may increase the risk for infections. During clinical trials, certain infections occurred more often in those taking Tysabri, including pneumonias, urinary tract infections, gastroenteritis, vaginal infections, tooth infections, tonsillitis and herpes infections. Q. I read that the FDA has included a “Black Box Warning” on Tysabri’s label. What does that mean? A. According to the FDA, a Black Box Warning is “ the most serious warning placed in the labeling of a prescription medication... Black box warnings are designed to highlight special problems, particularly those that are serious, and to give health care professionals a clear understanding of a potential medical complication associated with a drug. Black box warnings provide physicians with important insights as to how to prescribe a drug that may be associated with serious side effects in a way that maximizes its benefits and minimizes its risks.” The Black Box Warning for Tysabri warns of the increased risk of PML and the importance of monitoring patients using the drug for any new sign or symptoms that may be suggestive of PML. Q. Are any other side effects possible if I’m taking Tysabri? A. Yes. These will be detailed in the patient materials prepared by the drug’s sponsors. In a two-year clinical trial of Tysabri alone, some of the adverse events reported significantly more frequently in those on Tysabri included fatigue, allergic reaction, and hypersensitivity reactions. In a two-year clinical trial of Tysabri in combination with Avonex, adverse events experienced significantly more often in those on combination therapy included anxiety, sore throat, sinus congestion and peripheral edema (swelling). In addition, two cases of PML, one of which was fatal, were diagnosed in those on combination therapy. National MS Society’s Role in Advancing New

Treatments Q. What has the National MS Society done to advance the development of new drugs, including Tysabri? A. Since the Society’s founding in 1946, it has expended over $500 million to advance MS research, and has been at the core of virtually every major breakthrough in treating and understanding MS. Over the past 20 years, the National MS Society has invested over $13 million in 61 clinical studies of potential MS therapies. These investments in basic and applied MS research have made possible significant advancements towards finding effective treatments and improving diagnosis, rehabilitation, and symptomatic therapy for people with all forms of MS, as well as bringing us closer to a cure. For example, it was the Society who began funding the initial research into interferons and glatiramer acetate which led to the development of the current disease modifying medications Avonex, Betaseron, Copaxone, Rebif, and Novantrone -- the first therapies shown to affect underlying disease course. Q. Was the Society involved in the discovery of Tysabri? A. Yes. The significance of the integrin molecule, the study of which led to the development of Tysabri, was discovered as part of a Society-funded research fellowship. Q. What will the National MS Society do if additional people die or experience serious side effects after taking Tysabri? A. The use of Tysabri carries with it the risk of developing PML, an often fatal disease, and its use for extended periods of time carries unknown risks. If there are new cases, the National MS Society will monitor the situation and disseminate the information. If the risk for PML or other serious adverse events were to significantly rise in clinical use, we would advocate that the FDA take immediate and appropriate action. The National MS Society-Indiana State Chapter is proud to be a source of information about MS. Our comments are based on professional advice, published experience and expert opinion, but do not represent individual therapeutic

recommendation or prescription. For specific information and advice, consult your personal physician. We are excited about having this opportunity to provide you with the latest in advocacy on multiple sclerosis issues, and we hope you enjoy reading about it. If, however, you wish to be removed at any time, please let us know. Kraus Director of Chapter Programs National Multiple Sclerosis Society Indiana Chapter 7301

town Road, Ste 112 Indianapolis, IN 46268 www.nationalmssociety.org/ini 1-800-FIGHT-MS or (ext. 16) Fax: Everyone deserves reliable, affordable healthcare.This is why we advocate.Join our advocacy

action network at www.nationalmssociety.org/advocacy.asp or call 1-800-FIGHTMS

[Guest guest]

Neuro at Duke said it will be later this summer before they can

actually write prescriptions again for it.

From: DRiha15233@...

> Date: Tue, 6 Jun 2006 17:29:04 EDT

> Subject: Fwd: FDA Approves Tysabri's Return to Market

> To: cheri.furgason@...

>

>

>

> To: " 'Kraus' "

> Subject: FDA Approves Tysabri's Return to Market

> Date: Tue, 6 Jun 2006 08:33:10 -0400

>

> st1\:*{behavior:url(#default#ieooui) } You

have received this email because you have previously been in contact

with the National MS Society-Indiana State Chapter requesting

information. If you wish to be removed from this confidential list,

please reply back to this email requesting removal.

> -----------------------------------------------------------------

--------------------------------------

> June 5, 2006

>

> FDA APPROVES Tysabri's Return To Market For Relapsing MS

> -- Company Hopes to Make Drug Available in July

>

> The U.S. Food and Drug Administration has approved the return to

market of Tysabri® (natalizumab), produced by Biogen Idec and Elan

Pharmaceuticals, to delay the accumulation of physical disability

and reduce the frequency of relapses (clinical exacerbations) in

those with relapsing multiple sclerosis. The approval is based on

positive results from two clinical trials showing that Tysabri

significantly reduced the risk of sustained progression of

disability and the rate of clinical relapse in those with relapsing

MS.

>

> The approval hinges on a mandatory registration program for

patients and prescribing physicians to minimize the risks that

patients will develop PML (progressive multifocal

leukoencephalopathy), caused by a common virus called the JC virus.

Three people who had been in clinical trials involving Tysabri

developed PML, two of whom died. The drug, which is taken by monthly

IV infusion, will be dispensed at registered infusion centers across

the country.

>

> Tysabri is generally recommended for patients who have had

inadequate response to, or are unable to tolerate, other approved MS

therapies (such as Copaxone, ® Betaseron, ® Avonex, ® Rebif® and

Novantrone®). It is approved as a monotherapy, not to be combined

with other immune system-modifying agents, and is not recommended

for individuals who have compromised (weakened) immune systems.

>

> According to company sources, there will be a delay between the

time of FDA approval and the time when Tysabri is available to

patients. Several weeks are needed to develop training materials and

to finalize the patient data collection system. The companies hope

to commercially launch Tysabri, or make it available for use, in

July 2006. Individual patients may experience additional delays,

depending on the availability of a nearby registered infusion site

and any health insurance coverage issues.

>

>

> As part of its approval, the companies have agreed to conduct a

post-marketing study that will follow some 5,000 patients prescribed

Tysabri for five years to evaluate the long-term safety of the drug

in the clinical practice setting.

>

> " It's important that people with relapsing MS now have a new

treatment option, " said Dr. R. Richert, National MS Society

Vice President of Research and Clinical Programs. " We believe that

the mandatory patient registry and post-marketing observational

study will help clarify the potential risks and benefits of this new

therapy for people with MS, " he added.

>

> Key aspects of the approval include:

>

> · Tysabri is approved to delay the accumulation of

physical disability and reduce the frequency of clinical

exacerbations (flare-ups or relapses) in patients diagnosed with

relapsing MS;

> · Tysabri will only be available under a restricted

distribution program called TOUCH, and prescribing physicians and

patients must enroll in this mandatory registry program;

> · Tysabri can be given only at registered infusion

centers where the medical personnel have been trained in its proper

use and in the risks of PML;

> · Tysabri should be given as a monotherapy, meaning it

should not be combined with other medications that alter immune

function;

> · Tysabri is generally recommended for patients who have

had inadequate response to, or are unable to tolerate, other

approved MS therapies;

> · Tysabri is not recommended for patients who have

compromised (weakened) immune systems or who are taking other drugs

that suppress or modulate the immune system, with the exception of

periodic steroids to treat relapses;

> · Prescribing information carries a " Black Box Warning "

to highlight the increased risk of PML and the importance of

monitoring patients for any new signs or symptoms that may be

suggestive of PML.

> · An MRI scan must be obtained prior to starting

treatment with Tysabri;

> · Prior to each infusion, the patient and infusion nurse

complete a checklist to screen for symptoms suggestive of PML; and

> · Patients on Tysabri are to be evaluated by the

prescribing physician 3 and 6 months after the first infusion and

every 6 months thereafter, and their status will be reported to

Biogen Idec.

>

> Additional details about how and when Tysabri will become

available for infusion will be forthcoming.

>

> ü For information about the FDA approval, go to the FDA's

Web site at:

http://www.fda.gov/cder/drug/infopage/natalizumab/default.htm

> ü For Questions & Answers and other updated information from

the National MS Society, visit our Web site at

http://www.nationalmssociety.org/tysabri.asp.

> ü For further information about the availability of Tysabri,

individuals may call Biogen Idec's MS Active Source information line

at: 1-, or go to the Biogen Idec Tysabri information

site at http://www.biogenidec.com.

> -----------------------------------------------------------------

------------------------------------------

>

> Frequently asked Questions and their Answers

> concerning FDA APPROVAL OF tYSABRI

>

> About Tysabri and its Availability

>

> Q. What is Tysabri (pronounced Tie-SAB-bree) and how does it

work?

> A. Tysabri (whose scientific name is natalizumab, pronounced: nat-

tal-IZ-zue-mab) is a laboratory-produced monoclonal antibody. It was

formerly called Antegren. It had been approved for marketing by the

U.S. FDA for relapsing forms of MS, based on data from the first

year of two, 2-year clinical trials.

>

> Tysabri is designed to hamper the movement of potentially

damaging immune cells from the bloodstream, across the " blood-brain

barrier, " and into the brain and spinal cord. The drug inhibits this

movement by attaching to alpha 4-integrin, a protein on the surface

of immune T-cells that normally enables them to adhere to and pass

through the blood-brain barrier. Because of this mode of action,

Tysabri is called a selective adhesion molecule inhibitor

(or " SAM " ).

>

> This approach was initially studied in animal models, including

studies supported by the National MS Society, which showed that

monoclonal antibodies could block such immune cell movement and

ameliorate disease. These animal studies led to the successful human

studies.

>

> Q. Who should take Tysabri?

> A. Tysabri has been approved for persons with relapsing forms of

multiple sclerosis.

> Relapsing MS means that individuals experience flare-ups of

symptoms in the form of periodic attacks, which then subside with

total or partial recovery. Relapsing forms of MS may include those

with relapsing-remitting MS, progressive-relapsing MS, and those

with secondary-progressive MS who experience relapses.

>

> According to the FDA approval, Tysabri is generally recommended

for patients who have had inadequate response to, or are unable to

tolerate, other approved MS therapies. The question of who should

take Tysabri is something that can only be answered through

discussions between an individual and his or her neurologist.

>

> Q. In terms of who can be prescribed Tysabri, who determines

what constitutes an " inadequate response " to currently approved MS

therapies?

> A. The FDA's approval of Tysabri does not specifically

define " inadequate response, " nor does it define what constitutes an

inability to tolerate alternate MS therapies. Therefore, the

decision about whether to take or switch to Tysabri must be made

after careful consideration by a person with MS together with his or

her personal physician.

>

> Q. How long will I have to wait before I can take Tysabri?

> A. According to company sources, there will be a delay between the

time of FDA approval and the time when Tysabri is available to

patients. Several weeks are needed to develop training materials and

to finalize the patient data collection system. The companies hope

to commercially launch Tysabri, or make it available for use, in

July 2006. Individual patients may experience additional delays,

depending on the availability of a nearby registered infusion site

and any health insurance coverage issues.

>

> Q. How much will Tysabri cost?

> A. The price of Tysabri and any related tests or risk management

procedures has not yet been released. Prior to its withdrawal from

the market in 2005, the wholesale cost per vial was announced at

$1,808 (taken every 4 weeks, the yearly wholesale cost was $23,504).

>

> Q. Will my insurance cover the cost of Tysabri?

> A. Since Tysabri's approval is new, many health plans will

probably not be able to reach any conclusions about coverage yet.

Sometimes there is a lag time before a new drug is included as part

of a health plan's formulary. Prior authorization will probably be

necessary for most health plans. More information will be

forthcoming when details become available.

>

> Q. Does Medicare cover the use of Tysabri?

> A. Because Tysabri is an infusion given at a medical facility,

it will probably be covered by Medicare Part B.

>

> Q. How is Tysabri taken?

> A. Tysabri is given via monthly intravenous infusion at a medical

facility. As part of the risk management plan, Tysabri will be

available only at registered infusion centers. The companies

estimate that there will eventually be 2,000 such centers in the

United States . These may include doctor's offices, hospital clinics

and stand-alone clinics.

>

> Q. How long does an infusion take?

> A. The actual infusion takes about one hour. The overall visit

will take longer than that because of the risk management discussion

and paperwork that will need to be taken care of at the infusion

site.

>

> Q. Are infusions painful?

> A. A person getting an intravenous infusion will probably feel a

sharp pain or some discomfort when the needle penetrates the skin

and vein, but then the discomfort should subside as the infusion

proceeds. There may also be discomfort when the infusion needle is

removed and the site may or may not feel sore for a day or so.

>

> Q. Should I switch from the therapy I'm taking now?

> A. This question can only be answered through discussions

between an individual and his or her neurologist. The discussion

should focus on how well the individual is doing on his or her

current therapy and what is currently understood about the potential

risks and benefits of Tysabri.

>

> Q. I have relapsing MS and have never tried any of the disease-

modifying therapies. Will I be able to use Tysabri?

> A. The FDA recommends that Tysabri be used only in persons who

have had inadequate response to other approved MS therapies, or who

are unable to tolerate other approved MS therapies. This is a

question you should discuss with a neurologist who is knowledgeable

about MS and familiar with your condition and personal circumstances.

>

> Q. Can I switch to Tysabri if I'm on another MS drug right now?

> A. Possibly. This is a matter that should be discussed with your

neurologist. The prescribing information states that Tysabri should

not be given to patients whose immune systems are compromised, or

weakened. There will likely be a period of time between the end of

your current therapy and the beginning of Tysabri. The length of

time may vary depending on the type of therapy you are currently on

and the period necessary to " wash out " the current drug from your

system. If a person is currently using an approved MS therapy such

as Copaxone or interferon beta and is being switched to Tysabri,

the " wash out " period would probably be a few weeks before beginning

Tysabri infusions. If a person has recently been prescribed

Novantrone, Cytoxan, Imuran or other strong immune-suppressing drug,

the " wash out " period would be longer before beginning Tysabri. This

should be discussed with your neurologist.

>

> The FDA-approved prescribing information does not provide

specific recommendations for " wash-out " or waiting periods before

beginning treatment with Tysabri. However, for the post-marketing

study involving persons who had been enrolled in the original phase

3 studies of Tysabri (AFFIRM and SENTINEL trials), the FDA

recommends that anyone who has been taking an immune-modifying MS

drug (such as Copaxone, Betaseron, Avonex, or Rebif) should not

begin Tysabri for two weeks after the last dose, and that anyone who

has been taking an immune-suppressing drug (such as Novantrone,

Cytoxan or Imuran) should not begin Tysabri for three to six months

after the last dose.

>

> Q. How effective is Tysabri?

> A. In a two-year clinical trial of two years' duration (the

AFFIRM study) of Tysabri alone, 942 individuals received either

Tysabri or inactive placebo for more than two years. The treated

group experienced a 42% reduced risk of progression of disability, a

68% reduction of clinical relapses, and an 83% reduction in the

development of new or newly enlarging MRI-detected brain lesions.

Tysabri also reduced the mean number of enhancing (active) MRI

lesions by 92% after the first and second year. These results were

described in a published paper (The New England Journal of Medicine

2006;354:899-910).

>

> A second two-year trial of two years' duration (the SENTINEL

study) involved 1171 individuals with relapsing MS who were on

Avonex but had experienced at least one relapse during the previous

12 months. All participants continued on Avonex, in combination with

either Tysabri or inactive placebo given by intravenous infusions

every four weeks for up to 116 weeks. After one year, participants

who had Tysabri added to Avonex experienced a 54 percent reduction

in the rate of clinical relapses compared to those on placebo and

Avonex, which was also maintained at two years with a 55 percent

reduction.

>

> This combination therapy resulted in a 24 percent decrease in

the risk of sustained disability progression. MRI scans showed an 83-

percent reduction in the Tysabri plus Avonex group in enlarging MRI

lesions, and an 89-percent reduction in lesions showing active

inflammation. Results of this study were described in a published

paper (The New England Journal of Medicine 2006;354:911-923). Two

cases of PML, one of which was fatal, were diagnosed in those on

combination therapy.

>

>

> Q. What is meant by the statement that Tysabri should not be

taken by patients who have compromised immune systems or who are

taking other immunosuppressive or immunomodulatory agents?

> A. This means that Tysabri would not be used in patients whose

immune systems are weak, such as people who have MS and leukemia or

lymphoma, or who are taking immune-suppressing drugs or other MS

drugs such as interferons (Avonex, Betaseron, Rebif), Copaxone or

Novantrone. Other drugs sometimes taken by people with MS which may

weaken their immune systems include Cytoxan or Imuran, or monthly

intravenous steroids.

>

> There is no warning against the use of periodic steroids to

treat relapses in people taking Tysabri; however, the chronic use

of " pulse " or monthly steroids would possibly weaken the immune

system and therefore should probably be avoided.

>

> Q. Is Tysabri better than the other available MS therapies?

> A. Tysabri has not been compared head-to-head against any other

approved MS drug, and that is the only way to truly compare the

effectiveness of the MS drugs. However, generally clinicians agree

that the immunomodulatory drugs approved for use in MS reduce the

rate of relapses by about one-third. By contrast, after two years

Tysabri reduced the rate of relapses by about two-thirds as compared

to placebo. The investigators also reported that Tysabri reduced the

risk of sustained progression of disability over those two years.

These is some evidence that other approved MS drugs also slow

disease progression.

>

> It is important to note that since MS is such a diverse disease,

there is no " one size fits all " treatment strategy. Any decision

about whether to take any of the disease-modifying therapies should

be made after careful discussion between a patient and his or her

physician of its potential risks and benefits. The National MS

Society does recommend that upon diagnosis individuals with

relapsing MS consider early proactive treatment with one of the FDA-

approved therapies for MS that have been shown to impact the

underlying disease course.

>

> Q. Where can I call to get more information about Tysabri?

>

> ü For information about the FDA approval, go to the FDA's

Web site at:

http://www.fda.gov/cder/drug/infopage/natalizumab/default.htm

> ü For a summary of the approval announcement and other

updated information from the National MS Society, visit our Web site

at http://www.nationalmssociety.org/tysabri

> ü For further information about the availability of Tysabri,

individuals may call Biogen Idec's MS Active Source information line

at: 1-, or go to the Biogen Idec Tysabri information

site at http://www.biogenidec.com.

>

> Safety Concerns About Tysabri

>

> Q. What is the primary safety concern regarding the use of

Tysabri?

> A. A primary safety issue is the fact that three people who had

been in clinical trials involving Tysabri developed a rare disease

called PML (progressive multifocal leukoencephalopathy), caused by a

common virus called the JC virus. Two of them died, including one

person with MS.

>

>

> Q. If I take Tysabri, what are the risks that I will get PML?

> A. No one knows the true risk of getting PML outside of the

clinical trials of people taking Tysabri. According to a study

published in The New England Journal of Medicine (The New England

Journal of Medicine 2006;354:924-33), the risk in the clinical

trials population, who had taken an average of 17.9 doses of

Tysabri, is one in one thousand. Go to summary of these findings here

>

> There is not enough known about the true risk of getting PML in

people who may use Tysabri. For these and other reasons, Biogen Idec

and Elan have developed procedures for the careful tracking of

adverse events and has established a large observational study to

help evaluate the long-term safety of Tysabri.

>

> Q. Will I be safe if I take Tysabri alone, without any other

drugs that alter the immune system?

> A. No one knows. During the March 2006 advisory committee

meeting held by the FDA about Tysabri, FDA representatives stated

that the risk of PML in those who took Tysabri alone versus those

who took Tysabri in combination with Avonex is still unclear. That

means that at this time there is insufficient data to determine

whether PML was caused by taking Tysabri in combination with other

immune-modulating drugs, or whether PML can arise in those taking

Tysabri alone.

>

> Q. Are there any tests that can be done to know in advance

whether you are at risk for developing PML?

> A. No.

>

> Q. Are there any tests that can be done to know if you are

developing PML?

> A. Yes. If a person begins to show persistent signs of new or

worsening neurological symptoms, they would likely be taken off

Tysabri. Then their doctor would likely begin tests of the blood and

spinal fluid as well as obtain an MRI scan of the brain to help

determine whether the JC virus that causes PML is present and

active.

>

> Q. What are the signs of PML that a person using Tysabri should

look out for?

> A. All of this will be clearly explained in patient information

that will be supplied to individuals before they begin taking

Tysabri. Patients will be cautioned to inform their prescribing

physicians and/or infusion nurse if they experience any new or

worsening neurological symptoms. These might include any changes in

thinking, eyesight, balance, strength and other symptoms.

>

> Q. What is the treatment for PML?

> A. There is at present no drug that has been proven to fight the

JC virus. Therefore, treatment consists of reconstituting the immune

system by withdrawing any immune-suppressing therapies.

>

> Q. Are there risks of getting other serious infections if I take

Tysabri?

> A. The clinical trials of Tysabri in MS did not reveal significant

differences in serious infections between those on active treatment

versus those on inactive placebo. However, the risks of longer-term

exposure to Tysabri are currently unknown.

>

> FDA scientists reviewing safety data pointed out that Tysabri's

mode of action inhibits the recruitment of immune cells to sites of

infection, making it possible that risks of serious or opportunistic

infection may exist. According to the drug's labeling, the immune

system effects of Tysabri may increase the risk for infections.

During clinical trials, certain infections occurred more often in

those taking Tysabri, including pneumonias, urinary tract

infections, gastroenteritis, vaginal infections, tooth infections,

tonsillitis and herpes infections.

>

> Q. I read that the FDA has included a " Black Box Warning " on

Tysabri's label. What does that mean?

> A. According to the FDA, a Black Box Warning is " the most serious

warning placed in the labeling of a prescription medication... Black

box warnings are designed to highlight special problems,

particularly those that are serious, and to give health care

professionals a clear understanding of a potential medical

complication associated with a drug. Black box warnings provide

physicians with important insights as to how to prescribe a drug

that may be associated with serious side effects in a way that

maximizes its benefits and minimizes its risks. "

>

> The Black Box Warning for Tysabri warns of the increased risk of

PML and the importance of monitoring patients using the drug for any

new sign or symptoms that may be suggestive of PML.

>

> Q. Are any other side effects possible if I'm taking Tysabri?

> A. Yes. These will be detailed in the patient materials prepared

by the drug's sponsors. In a two-year clinical trial of Tysabri

alone, some of the adverse events reported significantly more

frequently in those on Tysabri included fatigue, allergic reaction,

and hypersensitivity reactions. In a two-year clinical trial of

Tysabri in combination with Avonex, adverse events experienced

significantly more often in those on combination therapy included

anxiety, sore throat, sinus congestion and peripheral edema

(swelling). In addition, two cases of PML, one of which was fatal,

were diagnosed in those on combination therapy.

>

> National MS Society's Role in Advancing New Treatments

>

> Q. What has the National MS Society done to advance the

development of new drugs, including Tysabri?

> A. Since the Society's founding in 1946, it has expended over $500

million to advance MS research, and has been at the core of

virtually every major breakthrough in treating and understanding MS.

>

> Over the past 20 years, the National MS Society has invested

over $13 million in 61 clinical studies of potential MS therapies.

These investments in basic and applied MS research have made

possible significant advancements towards finding effective

treatments and improving diagnosis, rehabilitation, and symptomatic

therapy for people with all forms of MS, as well as bringing us

closer to a cure. For example, it was the Society who began funding

the initial research into interferons and glatiramer acetate which

led to the development of the current disease modifying medications

Avonex, Betaseron, Copaxone, Rebif, and Novantrone -- the first

therapies shown to affect underlying disease course.

>

> Q. Was the Society involved in the discovery of Tysabri?

> A. Yes. The significance of the integrin molecule, the study of

which led to the development of Tysabri, was discovered as part of a

Society-funded research fellowship.

>

> Q. What will the National MS Society do if additional people die

or experience serious side effects after taking Tysabri?

> A. The use of Tysabri carries with it the risk of developing PML,

an often fatal disease, and its use for extended periods of time

carries unknown risks. If there are new cases, the National MS

Society will monitor the situation and disseminate the information.

If the risk for PML or other serious adverse events were to

significantly rise in clinical use, we would advocate that the FDA

take immediate and appropriate action.

>

> The National MS Society-Indiana State Chapter is proud to be a

source of information about MS. Our comments are based on

professional advice, published experience and expert opinion, but do

not represent individual therapeutic recommendation or prescription.

For specific information and advice, consult your personal

physician.

> We are excited about having this opportunity to provide you with

the latest in advocacy on multiple sclerosis issues, and we hope you

enjoy reading about it. If, however, you wish to be removed at any

time, please let us know.

>

> Kraus

> Director of Chapter Programs

> National Multiple Sclerosis Society

> Indiana Chapter

> 7301 town Road, Ste 112

> Indianapolis, IN 46268

> www.nationalmssociety.org/ini

> 1-800-FIGHT-MS or (ext. 16)

> Fax:

>

> Everyone deserves reliable, affordable healthcare.

> This is why we advocate.

> Join our advocacy action network at

> www.nationalmssociety.org/advocacy.asp

> or call 1-800-FIGHTMS

>