another oral drug up for approval

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another oral drug up for approval

Postby scorpion » Wed Sep 30, 2009 4:42 am

* On track for planned submission for approval



ZURICH, Sept 30 (Reuters) - Swiss drugmaker Novartis AG (NOVN.VX) said on Wednesday its FTY720 oral drug to treat multiple sclerosis reduced both relapses and disability progression.

Novartis's head of global development, Trevor Mundel, told reporters the group was on track to submit the drug for approval in the United States and Europe in December.

Mundel also said the study had not shown signs of new safety issues, which have been a concern with the drug.

Novartis shares were up 1.8 percent to 52.20 Swiss francs by 0746 GMT, outperforming a 0.7 percent rise in the DJ European pharmaceuticals sector index..SXDP

"The efficacy data published this morning confirm that FTY720 is superior to the current interferon-based gold standard of treatment," Vontobel analyst Andrew Weiss said in a note to clients.

"Given that the higher dose does not seem to add much benefit, it seems viable that Novartis will be filing only for application with the lower dose 0.5 mg," he said. "This is potentially good news as the safety profile is more benign at the lower dose," he said.

SAFETY

FTY720 has been associated with potentially fatal infections, skin cancer and a case of haemorrhaging focal encephalitis, an inflammation of the brain with bleeding. It is unclear whether the drug was responsible for the events. [nLT73514]

Novartis and German Merck KGaA (MRCG.DE) are leading the charge to develop MS drugs that can be taken orally, rather than by infusion or injection, but they must persuade physicians and investors the treatments are safe. [ID:nN24419113]

Novartis said initial results from the two-year Phase III study showed oral FTY720 was significantly superior to placebo in reducing both relapses and disability progression in patients with relapsing-remitting multiple sclerosis, one of the main causes of neurological disability in young adults.

Comprehensive analyses of the data were ongoing, and detailed results are planned to be presented at a leading scientific congress in 2010, Novartis said. (Reporting by Sven Egenter; Editing by Dan Lalor)
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Postby CureOrBust » Wed Sep 30, 2009 6:10 am

I've been waiting for these results. Now, when do we get it?
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Postby patientx » Wed Sep 30, 2009 6:32 am

Novartis said initial results from the two-year Phase III study showed oral FTY720 was significantly superior to placebo in reducing both relapses and disability progression in patients with relapsing-remitting multiple sclerosis, one of the main causes of neurological disability in young adults.


Not trying to be a damper, but in the video I posted in the previous thread, Dr. Coles had stated that FTY didn't show a significant difference in disability progression.
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Postby Needled » Wed Sep 30, 2009 6:44 am

Novartis' 3rd quarter conference call is on October 22. Maybe there'll be more info then. They don't usually give that kind of detail in the quarterly results, but you never know. I still haven't been able to find out if Novartis filed for Fast Track Approval for Fingolimod, like Merck did with Cladribine. That would be a big help in getting it through the FDA process. Does anyone know?
PX, the video was interesting, but I think the podcast that Dignan posted in January (thank you Dignan!) gave a lot more detail on all 5 of the new oral meds that are in various Phase III stages, including their history, effectiveness, side effects, etc. It’s about a ½ hour long, but well worth listening too, even though it’s a bit older now. Here’s the link -- http://www.thisisms.com/ftopict-6639-podcast.html
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Postby dignan » Wed Sep 30, 2009 9:00 am

Thanks for the update scorpion. Looks like it is on schedule. I'm glad to see confirmation that they are going to file for approval of the lower dose only. I still think they should do post-marketing trials of an even lower dose to see if they can find an even safer, effective dose.
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Postby Lyon » Wed Sep 30, 2009 1:34 pm

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Last edited by Lyon on Sat Nov 26, 2011 10:03 am, edited 1 time in total.
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Postby Needled » Wed Sep 30, 2009 2:06 pm

This was released today by Novartis on Fingolimod. There was also a webcast and the initial results were released in a 16-page document filled with info. I think everything's on this link -- http://www.novartis.com/newsroom/news/2 ... y720.shtml

September 30, 2009 07:15 CET

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.
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Postby Needled » Wed Sep 30, 2009 6:05 pm

I listened to the webcast, and during the Q&A session of the call, Novartis confirmed they will file the FDA application with a request for expedited review. They have been in close contact with the regulators all along since it’s been such a large study with so much data.
Has anyone else had a chance to review the data or listen to the call? I'd love to hear other thoughts/opinions.
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Postby dignan » Wed Sep 30, 2009 8:14 pm

Needled, I just listened to the webcast. I thought their explanations about side-effects (high blood pressure--not raised by much, cancer--low dose had fewer incidents than placebo in this study and infections--no serious infections) were reassuring and I didn't feel like they were spinning things.

Where I did feel a spinning sensation (I do have MS, so that could have just been my brain acting up...) was on the 2 questions they got about whether they would consider testing an even lower dose. The first answer they gave was that in the other phase 3, there was no difference at all in efficacy between 1.25 and 0.5, but in this study, there was a tiny difference in favour of 1.25, which I believe I read somewhere was NOT statistically significant. So they used that non-significant finding to say that they are starting to see a normal "dose response" e.g. a lower dose is less effective. So they don't want to try a lower dose that will probably be less effective. I call bull-shit on that.

The second answer was to say that they have some research data (not from clinical trials) on how the immunomodulatory effects of the drug change at even lower doses than 0.5mg and they believe that this would lead to lower effectiveness in lower doses. My thought is that their initial dose in the phase 2 trials was 5mg, which is ten times(!) the dose they are going to file for approval, so how much faith should we have in their lab results?!

So Novartis is not going to do anything about a lower dose, which leaves it up to the regulators to make them do something.
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