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http://www.novartis.com/newsroom/med.../1344775.shtml

Two-year Phase III study shows Novartis oral MS therapy FTY720 significantly reduces relapses and disability progression

* FREEDOMS study shows FTY720 reduced relapse rates by 54-60% compared to placebo, and disability progression by 30-32%[1]

* Results build on Phase III TRANSFORMS one-year study showing FTY720 reduced relapses significantly more than interferon beta-1a, a standard of care[2]

* Phase III efficacy and safety data confirm positive benefit-risk profile for lower 0.5 mg dose[1] and support planned submissions in US and EU at end of 2009

* Future development of FTY720 in relapsing forms of MS to focus on lower 0.5 mg dose

Basel, September 30, 2009 - Initial results from the two-year Phase III FREEDOMS study show that oral FTY720 (fingolimod) was significantly superior to placebo in reducing both relapses and disability progression in patients with relapsing-remitting multiple sclerosis (MS)[1] - one of the leading causes of neurological disability in young adults[3].

The FREEDOMS study met its primary and secondary endpoints for both the 0.5 mg and 1.25 mg doses, with no significant difference in efficacy between doses. This result builds on previous data showing superior efficacy to interferon beta-1a[2] in TRANSFORMS, the largest head-to-head Phase III study against a standard of care treatment in MS.

In FREEDOMS, FTY720 was generally well tolerated with a lower incidence of adverse events at the 0.5 mg dose than 1.25 mg[1]. Regulatory submissions for FTY720, planned in the US and EU at the end of 2009, will seek approval for the lower 0.5 mg dose based on comprehensive Phase III results establishing its positive benefit-risk profile. Future development of FTY720 in relapsing forms of MS will focus on the 0.5 mg dose.

"We are proud to have reached this critical milestone in the development of FTY720, a novel oral therapy that has the potential to transform the treatment of this ultimately disabling disease," said Trevor Mundel, MD, Global Head of Development at Novartis Pharma AG. "FTY720 0.5 mg therapy offers compelling efficacy on all relevant endpoints compared to both placebo and a standard of care, complemented by extensive safety data."

Results from the placebo-controlled FREEDOMS study show that FTY720 reduced the relapse rate by 54% for the 0.5 mg dose and 60% for the 1.25 mg dose compared to placebo (both p<0.001)[1]. In addition, FTY720 reduced the progression of disability by 30% for patients on 0.5 mg (p=0.024) and 32% for those on 1.25 mg (p=0.017) compared to placebo over two years[1]. These findings were supported by positive effects on brain lesions as measured by magnetic resonance imaging (MRI) scans.

FREEDOMS is the second of three Phase III studies to report results in the largest development program ever conducted in MS, involving more than 4,000 patients worldwide. Previously reported results from the one-year TRANSFORMS study showed a reduction in relapse rates of 52% and 38% for FTY720 0.5 mg and 1.25 mg respectively compared to interferon beta-1a (both p<0.001)[2]. FREEDOMS II, currently under way, is a two-year placebo-controlled Phase III study, similar in design to FREEDOMS.

"The positive results from the FREEDOMS study confirm the efficacy and safety of fingolimod, and provide important evidence of its effect on disability," said Professor Ludwig Kappos, Chair of Neurology and Research Group Leader in the Department of Biomedicine at the University Hospital in Basel, Switzerland, and the principal investigator of the FREEDOMS study. "As an oral therapy, it is clear that fingolimod potentially represents a significant advance in the treatment of MS."

FTY720 has a well-studied safety profile with more than 5,300 patient-years of exposure, including patients now in their sixth year of treatment. Previous data from the development program raised questions about potential side effects including macular edema, melanoma, liver injury, infections, and increased blood pressure. In the FREEDOMS study, at the 0.5 mg dose there were no cases of macular edema or melanoma[1]. Reversible and generally asymptomatic liver enzyme elevations were observed more frequently with FTY720 than placebo, and lung infections were also slightly more common[1]. Mild elevation in blood pressure was observed with FTY720. No new safety signals were seen in FREEDOMS compared to previous clinical trials. Three patients died during the FREEDOMS study, one on FTY720 1.25 mg and two on placebo. None of the deaths was assessed as being related to the study drug[1].

FREEDOMS (FTY720 Research Evaluating Effects of Daily Oral therapy in Multiple Sclerosis) was a double-blind, placebo-controlled study involving 1,272 patients in 22 countries to assess the efficacy, safety and tolerability of FTY720. The primary endpoint was reduction in annual relapse rate and the key secondary endpoint was reduction in disability progression, defined as an increase from baseline in Expanded Disability Status Scale (EDSS) scores confirmed at three months[1].

FTY720 has the potential to be the first in a new class of MS therapies called sphingosine 1-phosphate (S1-P) receptor modulators. Comprehensive analyses of the FREEDOMS data are ongoing, and detailed results are planned to be presented at a leading scientific congress in 2010.

Disclaimer
The foregoing release contains forward-looking statements

~HappyPoet (aka Annie1234 at BT)

P.S. I originally posted this earlier today on BrainTalk

Hi HP, Scorpion also posted this yesterday in the Drug Forum. And then Novartis released the detailed Phase III trial results later in the day. Here's the link to that post, including Dignan's thoughts on the webcast. Thank you Dignan! And now I have to go check out BrainTalk, too...
http://www.thisisms.com/ftopict-8290.html

Hi Needled,

I thought about posting it there, too, but I couldn't find the right spot. The pipeline thread mentioned Phase I and II info only, so I put it here. Now, I have to go check out the link you so kindly gave me. Thanks so much.

I thought no one here liked me because there were no replies -- if not for you, I would never have visited TIMS again, so I thank you again for taking the time to let me know

~HP

Any idea when this will be available?

HP, Since the post was already in the Drug Forum, I just added to it. It's very important information, so it could have gone in either place. Anyway, if you could, let us know what's going on over at BrainTalk. I went over there earlier, but it felt like sneaking around in someone else's house and opening their cabinets looking for stuff. I couldn't find anything. I'd be interested in their take on the trial info and webcast. Thanks!

Kathryn, Novartis says they're still on track to file with the FDA in the U.S. by the end of 2009. They have been granted expedited review by the FDA. That means the review process is sped up as the company has been in contact with the FDA during the trial process, so it's not all new to the FDA. A priority review used to be an average of 3-6 months, but I'd read somewhere recently that timeframe has expanded up to 9 months. And that's certainly not a guarantee. Who knows what the FDA could come back and ask for? But if Novartis files on December 31 (earlier would be nice, but let's not push it!), the FDA could conceivably give their decision anytime after April 2010. I would love for it to be an approval and for that to happen so soon, but I'm still thinking sometime during the summer/maybe as late as fall. It's all just a big guestimate.

Okay, thanks! I need something new and this or cladribine seems like a good choice. Copaxone just doesn't seem to be working for me anymore.

This new medication poses a real threat to the established minimally effective CRAB drug group as well as to Tysabri. Because of the huge amount of money that is involved here, I would unfortunately expect the makers of the CRABs and Tysabri to "circle the wagons" and begin taking steps to protect their cash cows against a drug that can be taken orally.

It looks like finally MS patients may have the opportunity to avoid all those needles and nasty side effects from the drugs that they have had to live with for several years.

Has anyone heard yet as to the cost per month of purchasing FTY720?

Harry

Harry, I wouldn't get too excited about the new oral drugs not having side effects...I am sure they have their own major risks in other ways. My biggest worry with these oral drugs are
A. What effect they have on the liver
B. If they increase the risk of cancer. (if its a small risk raise then I am not fussed and will take the chance if it triples the chances or something then I will worry!)

Harry, In April 2009 during the AAN conference, Elmar Schnee, head of Merck's pharmaceuticals business and member of its executive board, talked briefly about Cladribine's pricing. He said that despite Cladribine's infrequent dosing and being a pill, rather than a biologic, Merck will likely be aggressive in pricing the drug.

"I think that pricing has to be in line with the benefits that the drug brings to the patient," Schnee said. "It doesn't differ if you have an injectable or if you have a tablet." The article went on to say that Biogen's Avonex, the MS market leader, is currently sold for about $30,000 a year.

I would be pleasantly surprised if other pharm companies didn't follow Merck. I'm afraid the pills are going to cost as much as the injectibles. I thought I had read somewhere in the new Novartis information about how much they had spent on developing Fingolimod, but I can't find it right now. I understand that they have to recover the millions of dollars invested in research and trials, but still, it gets me mad and sad. Just part of the same old MS rollercoaster ride, I guess...

Here's the link to the full article, definitely worth reading because it also talks about Cladribine's side effects -- http://www.marketwatch.com/story/merck- ... -effective

HarryZ wrote:Because of the huge amount of money that is involved here, I would unfortunately expect the makers of the CRABs and Tysabri to "circle the wagons" and begin taking steps to protect their cash cows against a drug that can be taken orally.
Harry

I'm not so sure about this. Each of the DMD manufacturers is developing its own oral med for MS. So, while those behind in the pill competition might try to forestall things, I think they all see the writing on the wall.

LR1234 wrote:Harry, I wouldn't get too excited about the new oral drugs not having side effects...I am sure they have their own major risks in other ways. My biggest worry with these oral drugs are
A. What effect they have on the liver
B. If they increase the risk of cancer. (if its a small risk raise then I am not fussed and will take the chance if it triples the chances or something then I will worry!)

I guess it depends on the level of the side effects. Any time you take a drug that effects the way the immune system functions, you open up the opportunity for other problems to surface. And the liver is usually the first organ to "complain".

There is a race by big pharma to get the first oral MS medication approved because being first will generate huge revenues. I just hope that the efficacy numbers being published turn out to be accurate!

Harry

'"I think that pricing has to be in line with the benefits that the drug brings to the patient," Schnee said. "It doesn't differ if you have an injectable or if you have a tablet." The article went on to say that Biogen's Avonex, the MS market leader, is currently sold for about $30,000 a year.

As is the case with most drug companies, they base their price on predicted benefits and the numbers they quote to substantiate the price aren't always accurate. Or the companies don't necessarily spend much time and effort telling the public all the possible problems that they know about. Look at Tysabri's introduction a few years ago!

I would be pleasantly surprised if other pharm companies didn't follow Merck. I'm afraid the pills are going to cost as much as the injectibles. I thought I had read somewhere in the new Novartis information about how much they had spent on developing Fingolimod, but I can't find it right now. I understand that they have to recover the millions of dollars invested in research and trials, but still, it gets me mad and sad. Just part of the same old MS rollercoaster ride, I guess...

Other big pharmas will definitely follow Merck. It all has to do with huge revenue generation and little with what benefits MS patients the most.

Harry

I'm not so sure about this. Each of the DMD manufacturers is developing its own oral med for MS. So, while those behind in the pill competition might try to forestall things, I think they all see the writing on the wall.

Not only forestall but they will try and discredit the other company's product. You will see head to head trials which will cost millions of dollars in an effort to "prove" my MS drug is better than yours! And guess who will pay for these trials??!!

There are millions and millions of $$$ at issue here and the marketing and sales of these oral drugs is going to be a giant battle field.

Harry

PX, I always appreciate your thoughts and comments, and I think it's exactly because it is a race that things will get ugly. So I have to agree with Harry on the pricing issue. There are billions of dollars involved here. Nobody's going to play nice. In the 2nd quarter of 2009, TEVA reported the following on Copaxone:

Record global in-market sales of Copaxone® of $682 million, up 21% compared to the second quarter of 2008. Copaxone® continues to be the leading MS therapy in the U.S. and globally.

How happy is TEVA going to be when I switch to Fingolimod? Their pill won't come out for at least a couple more years. I couldn’t understand how Teva/Copaxone could possibly justify the outrageous price increases for the 3+ years I’ve been taking it, or what they were basing it on since there have been absolutely no changes to the drug and it’s been on the market for years. Then when I read Schnee’s comment, it all made sense (at least in my twisted mind). Big Pharma has been jacking up the CRABS so they can use the same pricing for the pills when they come to market. This way they recover the costs for a new pill and don’t loose any money in the transition from “blockbuster” status drugs to pills. At least, that was my take on Schnee’s comment. Just my 2 cents, which is worth absolutely nothing. The good news is I’m thrilled that soon we’ll have more options. I know we have to pay for them, but the bad news is I’m just not sure how long I’ll be able to afford them.