This Is MS Multiple Sclerosis Community: Knowledge & Support

Full data will be released at AAN in april but here is the news release:

TYSABRI-R- Two-Year Monotherapy Trial Demonstrates Significant Impact on Disability Progression and Relapse Rate in Multiple Sclerosis
Thursday February 17, 2:30 am ET


CAMBRIDGE, Mass. & DUBLIN, Ireland--(BUSINESS WIRE)--Feb. 17, 2005--
Data Show 42% Reduction in the Risk of Disability Progression and Sustained 67% Reduction in Relapse Rate

Biogen Idec (NASDAQ: BIIB - News) and Elan Corporation, plc (NYSE: ELN - News) announced today that the Phase III TYSABRI® (natalizumab) AFFIRM monotherapy trial achieved the two-year primary endpoint of slowing the progression of disability in patients with relapsing forms of multiple sclerosis (MS). TYSABRI treatment led to a 42 percent reduction in the risk of disability progression relative to placebo. These data also demonstrated a 67 percent reduction in the rate of clinical relapses over two years, which was sustained and consistent with the previously reported one-year results.


Other data from AFFIRM at two years, including MRI measures and immunogenicity were similar to previously reported results.

The adverse event profile at two years was also consistent with previously reported results. Common events included headache, fatigue, urinary tract infection, depression, lower respiratory tract infection, limb and joint pain, and pharyngitis. The incidence of infections in TYSABRI-treated and placebo-treated patients was similar. Serious infections occurred in 3.2 percent and 2.6 percent of patients, respectively. These included bacterial infections such as pneumonia and urinary tract infection, which responded appropriately to antibiotics. TYSABRI has also been associated with hypersensitivity reactions, including serious systemic reactions that occurred at an incidence of less than 1 percent of patients.

"TYSABRI, with its significant effect on slowing the progression of disability, offers new hope for patients with MS," said Burt Adelman, MD, executive vice president, Development, Biogen Idec. "With these data, we gain a more complete understanding of the broad therapeutic benefit of TYSABRI in MS."

"Results from the two-year monotherapy clinical trial mark a major milestone in the treatment of MS. These two-year data strengthen our belief that TYSABRI will become the leading therapy for MS patients," said Lars Ekman, MD, executive vice president and president, Research and Development, Elan.

AFFIRM is a two-year, randomized, multi-center, placebo-controlled, double-blind study of 942 patients conducted in 99 sites worldwide, evaluating the effect of TYSABRI on the progression of disability as measured by the Expanded Disability Status Scale (EDSS) and the rate of clinical relapses. Patients were randomized to receive either a 300 mg IV infusion dose of TYSABRI (n=627) or placebo (n=315) every four weeks.

Based on one-year data from AFFIRM and the SENTINEL add-on trial with AVONEX® (Interferon beta-1a), the U.S. Food and Drug Administration (FDA) granted Accelerated Approval for TYSABRI on November 23, 2004, as a treatment for relapsing forms of MS.

The companies anticipate that two-year data from the AFFIRM trial will be presented at the American Academy of Neurology (AAN) meeting in April 2005. The companies expect two-year results from the SENTINEL trial will be available mid-year. Two-year data from both studies will also be submitted to regulatory authorities.

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Davy's on the 2yr AFFIRM Data

Tysabri impresses on two-year AFFIRM data

jack.gorman@davy.ie

• As expected, Elan has issued headline data from the two-year AFFIRM study ahead of full presentation at AAN in April
2005.

• The results are very good. Tysabri met its primary endpoint of slowing the progression of disability. It demonstrated a 42%
reduction in the risk of disability progression relative to placebo (Rebif has shown 22–30% reductions and Avonex up to 37%
reduction in other differently structured trials). This was achieved with high significance. The relapse rate reduction was
sustained at 67% over the two years, same as after one year and is a positive surprise. Encouragingly, the adverse event
profile is also consistent with one-year data (i.e. modest).

• This headline data confirms that Tysabri's two-year data is very strong. As such, the product sustains its clear lead over
competitors with regard to relapse reductions, and now has exceeded them on disability as well. This will help convince
neurologists that the product is safe and effective over a longer time period, and will underpin revenue forecasts.
.

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Bloxham comment on the 2yr AFFIRM Data.

This morning Elan released the headline data from its two year phase three clinical trials for Tysabri for MS. The AFFIRM trials met their secondary endpoints with a 42% reduction in risk of disability progression and a 67% reduction in the relapse rate.

These results are consistent with the one year data. The release of this data begins to put clear blue water between Tysabri and the other MS treatment which have a lower impact on MS’s disease progression and relapse rates. When this better efficacy is combined with Tysabri’s stronger safety profile, Biogen’s CEO recent claims that Tysabri can take at least 50% of the MS market may prove conservative. 2000 out of the target 6000 neurologists have prescribed Tysabri at least once, the 4000 US neurologists who have yet to prescribe Tysabri may have been waiting for two year data before commencing prescriptions.

Today’s news flow goes a long way towards reducing the uncertainty about Tysabri and its long term effectiveness. With 3000 patients by January end already on Tysabri and another 9000 awaiting infusion, today’s news flow switches the issue facing Tysabri from sales trajectory to production capacity constraints.

The recent 4Q conference calls highlighted that Biogen is only expecting to produce enough supply for 40,000 patients in 2005. Today’s headline goes a long way towards driving the Tysabri rollout rapidly towards that upper limit, which would equate to $940m in sales.
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The summary of a SG Cowen note on Biogen Idec today:

ELN/BIIB....AFFIRM trial results superb

February 17, 2005

Biogen Idec (BIIB)


Positive 2-Year Data Position Tysabri To Own The MS Market
Conclusion: Biogen Idec and partner Elan reported 2-year data from Tysabri's AFFIRM monotherapy trial. The results indicate Tysabri reduced the risk of disability progression by 42%. This figure eclipses the highest previous reported reduction in the risk of disability for a multiple
sclerosis drug. Tysabri also showed a 67% reduction in relapse rate versus
placebo at two years, a result that is very consistent with the one year data.

We believe the positive 2-year data position Tysabri as superior to all other MS therapies and expect the drug to achieve our Street high sales estimate of $4B in 2009. We view BIIB as the best growth stock in the biotechnology sector.

Tysabri Sets A New Standard In Disability. Tysabri's 42% reduction [in] the risk of disability progression versus placebo at 2 years is modestly better than the previous record set by Avonex (37% reduction). Rebif's label indicates a 30% reduction in disability progression at two years while Betaseron and Copaxone have never shown an impact on progression.

Tysabri Clearly Superior On Other Endpoints. At two years, Tysabri demonstrated a 67% reduction in relapse rate versus placebo. This result is consistent with the 1-year data and far superior to the
approximately 30% reduction in relapse rate demonstrated by other agents at 2 years. MRI measures also positively impacted at 2 years.

Biogen and Elan characterized immunogenicity data as consistent with the one year results, indicating roughly 10% of patients may be inappropriate for therapy based upon antibody formation to drug.
Tysabri's safety profile continues to be excellent at 2 years. Full 2-year data will be presented at the AAN meeting in April.
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great research! we've covered the release on the front page:

http://www.thisisms.com/modules.php?nam ... =0&thold=0

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Disclaimer: Any information you find on this site should not be considered medical advice. All decisions should be made with the consent of your doctor, otherwise you are at your own risk.

Just want to make the point that comparison's on disability reduction with Tysabri against the other therapies is not valid. The Tysabri data is reporting reduction in RISK of disability progression, not the real efect on disabilty as mesaured by progression on the EDSS scale (which is how disability was reported in the other trials). Lets remember that we need to compare appropriate outcome measures. Unfortanately, comparisons are being made across different trials which is not valid. For example, you cant compare disability reduction between Rebif and Avonex pivotal trials b/c the Avonex trial really only measured mild disability because the EDSS inclusion criteria was only up to 3.5 while the Rebif trial was up to 5.0- a big difference.

The Tysabri press release does not share absolute numbers which is important to know because of how the placebo arm responded. The placebo arm in the AFFIRM trial did very well. It makes you wonder how Tysabri would do in a patient that was progressing, or futher along in their disease. I dont want to rain on this parade, let's just wait until this data is published and peer reviewed.

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Prudential Report Today on Tysabri.

HIGHLIGHTS

• This morning Biogen Idec and partner Elan released the top line 2 year data from the AFFIRM monotherapy trial.

• While not directly comparable to competitive compounds, the data from AFFIRM appears consistent with the 1 year data in terms of reduction in relapse rate and safety.

• By our analysis, the reduction in relapse rate for both the one year and 2 year data appear to be approximately twice that of each of the interferon compounds (Avonex, Rebif and Betaseron), as well as Copaxone.

• With respect to disability progression, Tysabri demonstrated a hazard ratio of 42% compared to placebo. Recall that neither Betaseron nor Copaxone have a disability claim in their respective labels.

• We learned from Biogen Idec management that when the full data set is presented at the upcoming AAN (American Academy of Neurology) on April 12 and 13 in Miami, the data will be sliced in various ways which will allow a direct comparison to the labels of the competitive compounds listed above.

• We view this as an indication of Biogen Idec confidence in the superiority of their data over the competitive set.

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A two year trial has demonstrated the efficacy of Tysabri in RRMS.


http://www.commentwire.com/commwire_sto ... re_ID=6376
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Typical of Biogen- slicing the data.

Bebe,



Glad that there is someone out there who knows how to interpret this data and recognize just what Biogen is doing here. They are masters at this kind of press release but most MS professionals recognize exactly what is being done. I guess when marketing people see just how much money exists at the end of the MS med rainbow, they will do almost anything to ensure that they "get it".

Harry

Bebe and HarryZ,

I'm not sure you understand what "slicing the data means" in statistics lingo.
The only way we can tell if Tysabri is any better at reducing disability than CRABs is by trying to analyze it the same way it was done in the trials that used the CRABS (i.e., slicing it differently).

HarryZ, I thought you'd be happy - you were forever complaining that:

1.) There's no disability data
2.) They're not releasing the 2-year data.
3.) The FDA shouldn't have approved it, and the 2-year data will be different.

Now, granted, I may be biased toward that drug, since it's my wife only real hope of staving off MS using current drugs.
But surely, isn't it time to express some joy at the good news?

Although Biogen and Elan are in it for the money, It doesn't mean that they are evil treacherous conglomerates conspiring to sell a useless potion to the masses for a fortune.
Being in research myself, I'll bet you that the scientist who developed this (not the marketing types) are happy for the patients.
It really makes a difference when you know your hard work improved someone's life.

Guy


Guy

Dr. Guy,



That's the problem...you can't slice it differently because the trials were designed differently. But Biogen tried to compare their trial results between Tysabri and the other MS meds and state that their results were better. As Bebe stated, you can't compare them. But in the world of marketing, that doesn't mean much as long as the people reading your press releases don't know any differently!



Not sure that I would use the word "complaining"...perhaps concerned about the incomplete data would be much better

1) The disability data I am looking for is the EDSS scores which I am told is the real measurement for these drugs. From what I have been told by people in MS medicine,that did not improve in the trials. Biogen has still not published that data yet.

2) I've never "complained" that Biogen didn't release the two year data....only the fact that it had not been released to give the MS peer group a chance to review it. It is now starting to come out, mind you not in publications as yet but in Biogen press releases.

3) I've never said the FDA should not have approved Tysabri...only that the approval of the drug based on one year data was very unordinary when it came to the approval of Tysabri. Almost every MS professional that I have spoken to or read comments about have all said the same thing! And when you look at the current situation that the FDA has found itself in with a variety of problems with other "approved" drugs, you have to wonder about their process with Tysabri.



With all the suffering that I have seen MS patients endure over the years, I, as much as anyone else affected by this disease, welcome any good news that helps people with this disease. At the same time there is nothing worse than promoting the heck out of a drug for any kind of illness before you have all your homework done. I've been told by a number of MS medical people that the homework was not completed and that this is not the process to follow when it comes to drug development. Who knows, perhaps in the long run, Tysabri will turn out to be an excellent drug for certain kinds of MS patients and the days of having to endure the problems associated with the CRABs will be greatly reduced.


As for Biogen's game plan...well, those in the field of medicine already know them and how they operate. Nothing more needs to be said.

Harry

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From National MS Society

Companies Release Results of Completed 2-Year Trial of Tysabri in MS

February 17, 2005

Biogen Idec and Elan Corporation today announced the successful completion of a two-year clinical trial of Tysabri® (natalizumab, formerly known as Antegren) in relapsing forms of multiple sclerosis. According to a company press release, the two-year trial achieved its primary outcome by slowing the risk of progression of disability by 42 percent.

The release also confirmed that the drug reduced the rate of clinical relapses by 67% over two years, and continued to reduce the development of new or newly enlarging MRI-detected brain lesions, findings that are consistent with the previously released results of the first year of the trial. Progression of disability was measured using the EDSS (Expanded Disability Status Score), which measures walking ability and other neurologic function.

The companies have announced that details of the two-year AFFIRM results will be presented at the American Academy of Neurology meeting in April, and that the two-year data will be submitted to the FDA and other regulatory agencies.

According to the companies, the safety profile of Tysabri over two years was consistent with findings announced for the first year. Common side effects included headache, fatigue, urinary tract infection, depression, lower respiratory tract infection, limb and joint pain and sore throat. The overall incidence of infection was similar between those on Tysabri and those on placebo. Serious infections, such as pneumonia and urinary tract infection, occurred in 3.2 percent of participants on therapy and in 2.6 percent on inactive placebo. Tysabri has been associated with hypersensitivity reactions, including serious systemic reactions that occurred at an incidence of less than 1 percent of patients in the trial. Longer term safety information is not available.

The “AFFIRM” trial was placebo-controlled and involved 942 participants from around the world. In November 2004, the U.S. Food and Drug Administration approved Tysabri for relapsing forms of MS based on first-year results of the AFFIRM trial and of a second trial, “SENTINEL,” which adds Tysabri to Avonex® (interferon beta-1a) therapy. The companies expect results from the SENTINEL trial by mid year.

Unlike other drugs that have already been approved for treating MS, Tysabri is a monoclonal antibody that is given by infusion into a vein every 4 weeks. It is designed to interfere with movement of potentially damaging immune cells from the bloodstream, across the “blood-brain barrier,” and into the brain and spinal cord. Tysabri inhibits this movement by attaching to alpha 4-integrin, a protein on the surface of immune T cells that normally enables them to pass through the blood-brain barrier. 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.

Commentary: The fact that Tysabri has been shown to be safe and effective over two years against both relapses and progression is excellent news for persons with MS. The National MS Society looks forward to reviewing the full data when they become available.

http://www.nationalmssociety.org/Resear ... eb17-2.asp
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Biogen-Idec and Elan just told you that disability progression as measured by EDSS scores showed Tysabri patients did far better than placebo group. The companies said they would release full data at AAN in April.

People in MS Medicine... more mysterious people with information that continues to be contradicted by released data, by anecdotes told by real patients here and on other MS boards, and by the companies themselves.

Quote: Tysabri has been associated with hypersensitivity reactions, including serious systemic reactions that occurred at an incidence of less than 1 percent of patients in the trial.

It will be interesting to see the data on this when they release the "full" results of the trials.