FDA Fast Track KNS-760704 for ALS

[rocmg]

PITTSBURGH--(Business Wire)--
Knopp Neurosciences Inc. announced that it received Fast Track designation from
the U.S. Food and Drug Administration (FDA) for the development of KNS-760704 in
amyotrophic lateral sclerosis (ALS).

Knopp has completed the randomized, placebo-controlled portion of its Phase 2
studies of KNS-760704 in 102 ALS patients and expects to initiate Phase 3
studies in the U.S. and Europe in 2010. Subjects who completed the Phase 2
program were offered enrollment in an ongoing, 48-week open-label safety
extension in which all participants are receiving the highest dose tested of
KNS-760704.

The Fast Track Program was created to facilitate the development and expedite
the review of new drugs with the potential to meet unmet needs in serious or
life-threatening conditions. ALS is a universally fatal disease of progressive
paralysis with limited treatment options.

"Knopp Neurosciences is very pleased to receive Fast Track designation and the
recognition that KNS-760704 holds the potential to address unmet needs in ALS,"
said Michael Bozik, M.D., president and CEO of Knopp. "We are pursuing every
available opportunity to accelerate the development of KNS-760704, and will take
full advantage of the opportunities under Fast Track to work with the FDA in
designing a program to demonstrate the drug`s safety and efficacy."

About KNS-760704

KNS-760704 is a low molecular weight benzothiazole shown to improve
mitochondrial function and to confer significant cellular protection in neurons
under stress. The chirally pure form of the synthetic benzothiazole
(6R)-2-amino-4,5,6,7-tetrahydro-6-(propylamino)benzothiazole, KNS-760704 is
highly orally bioavailable, water soluble, renally excreted, and only moderately
protein bound. In Phase 1 studies, the compound was shown to be safe and well
tolerated in healthy human subjects. KNS-760704 has received orphan drug
designation from the U.S. Food and Drug Administration and the European
Medicines Agency for the treatment of patients with ALS.

About ALS

Amyotrophic lateral sclerosis, also known as Lou Gehrig`s disease and Charcot`s
sclerosis, is a rapid, universally fatal neurodegenerative disorder
characterized by progressive muscle weakness and wasting. ALS affects adults in
the prime of life and creates a substantial burden for caregivers. U.S.
prevalence is approximately 20,000 and the global incidence is approximately two
per 100,000. Worldwide prevalence estimates of ALS range from 2 to 9 people per
100,000. Only one drug has been approved for the treatment of ALS. Life
expectancy after symptom onset is usually three to five years.

About Knopp Neurosciences Inc.

Knopp Neurosciences is a drug discovery and development company focused on
delivering breakthrough treatments for neurological disorders through
innovation, experience, and partnership. The company`s lead product candidate is
KNS-760704, an orally bioavailable small molecule in development for the
treatment of ALS. Knopp`s leadership includes experienced neuroscience drug
development and discovery executives formerly associated with major
pharmaceutical companies. Knopp`s financing has been led by Saturn Capital Inc.
of Boston as placement agent and Saturn Partners II as lead funder.

This press release contains "forward-looking statements," including statements
relating to Knopp`s planned regulatory filings and clinical development programs
for KNS-760704. All forward-looking statements are based on management`s current
assumptions and expectations and involve risks, uncertainties and other
important factors, specifically including the uncertainties inherent in clinical
trials and product development programs, the availability of funding to support
continued research and studies, the availability or potential availability of
alternative therapies or treatments, the availability of patent protection for
the discoveries and strategic alliances, as well as additional factors that may
cause Knopp`s actual results to differ from our expectations. There can be no
assurance that KNS-760704 will be successfully developed or manufactured or that
final results of clinical studies will be supportive of regulatory approvals
required to market the products. Knopp undertakes no obligation to update or
revise any such forward-looking statements, whether as a result of new
information, future events or otherwise.





Knopp Neurosciences Inc.
Tom Petzinger, 412-488-1776
Executive Vice President, Business Development and Public Affairs
[email protected]

Copyright Business Wire 2009

 

[thelma313]

Wow, thanks for sharing this!

 

[Big Mike]

Good post, rocmg. Hopefully, this is a good sign that the drug has strong potential and will come to fruition as a powerful new treatment.

 

[rocmg]

that's the hope Mike... the only thing that perturbs me about the drug is that lithium had the same scientific minds behind it, and i think it also was fast tracked by the FDA. maybe the medical researchers are just as desperate as the patients to find something that works.

 

[Big Mike]

I hope that fast track designation means just that--fast. Does anybody know how much quicker such a designation would bring the drug to commercial use, assuming it is shown effective.

 

[Danijela]

Here is a non jargon entry published by MNDA (UK)


Researchers report on encouraging trial results of KNS-760704
09 December 2009
At the second day of the 20th International Symposium on ALS/MND, researchers have presented the encouraging results of a Phase 2 clinical trial looking at the safety and tolerability of a drug called KNS-760704 in ALS patients. ALS (Amyotrophic Lateral Sclerosis) is the most common form of motor neurone disease (MND).

The results were presented by Dr Merit Cudkowicz, an associate professor of neurology at the Massachusetts General Hospital of Harvard Medical School. Dr Cudkowicz is an expert in co-ordinating MND clinical trials in the USA.

The two-part Phase 2 trial found that KNS-760704 was safe and well-tolerated in ALS patients for up to nine months. The trial results also showed trends suggesting the potential for reducing the rate of decline in the functional capability of patients, for example, how far people can walk unaided, lifting objects, dexterity in eating; and survival.

The researchers emphasised that KNS-760704 is still in the early days of development for patients and that further testing in a large, longer-term, carefully-monitored Phase 3 trial is needed to establish the necessary evidence that the drug is both safe and effective for ALS patients.

“We are very encouraged by the results presented today in Berlin and, at the same time, we’re acutely aware of the work that remains to be done,” said Dr Michael Bozik, president and CEO of Knopp Neurosciences Inc, the pharmaceutical company behind the development of KNS-760704.

In Part 1 of the trial, 102 patients received the treatment or the placebo every day for 12 weeks. Patients taking KNS-760704 received the drug in one of three doses - low, medium or high. KNS-760704 showed a dose-dependent trend in slowing the rate of disease progression with the greatest benefit observed in the high dose group.

In Part 2 of the trial, 92 patients were randomly assigned to receive low or high doses of KNS-760704 for 24 weeks. In addition to results again suggesting a dose-dependent trend in slowing the rate of disease progression there was also a trend toward a survival benefit in the high group compared with the low dose group.

Dr Belinda Cupid, research manager at the MND Association who attended the announcement, explains: “Phase 2 clinical trials determine the size of the dose, the timing of the dose and how the drug is to be taken for the next phase of testing.

“Although Phase 2 testing provides some indication of a drug’s ability to treat a disease, the number of patients involved at this stage is much too small for the findings to be relied upon.

“Phase 3 clinical trials are important as they aim to show whether or not the drug actually has a beneficial effect on patients. This stage of testing will usually involve hundreds of patients which is enough to allow a reliable assessment of the drug’s effectiveness. Phase 3 results will determine whether or not a drug is to be approved to treat a disease."

She continues: “Researchers know that MND is caused by motor neurones dying but what we are now trying to find out is what goes on in these cells before they die.

“We are looking inside these cells as we believe that the compartments which supply energy in the motor neurones are one of the main culprits. Evidence is building to show that when the energy supply goes wrong, MND develops. KNS-760704 acts by improving the energy supply within motor neurones.

“It’s promising news to hear that KNS-760704 will now be tested for its beneficial effects in people with MND."

Phase 3 testing of KNS-760704 in ALS may begin in mid-2010 at sites in Europe and North America under a protocol under development by Knopp Neurosciences Inc., in consultation with global regulatory authorities.

If you are affected by MND and would like to know more about the development of KNS-760704, please contact Knopp Neurosciences Inc. at [email protected].

Contact:
For media enquiries please contact Louise Coxon Communications Manager
01604 611843 / 07760 765142
[email protected]
Notes to editors
The 20th International Symposium on ALS/MND is taking place in Berlin, Germany from 8 to 10 December.

 

[rocmg]

i can't comment on that account... i know that Knopp are trying to get the phase 3 trial started as quickly as possible in 2010...

At first it was thought to being in the first quarter, now it seems likely it will be first half of 2010 -- but they say they're working on it, trying to quicken the pace.

 

[thelma313]

"KNS-760704 is a low molecular weight benzothiazole shown to improve
mitochondrial function and to confer significant cellular protection in neurons
under stress. "

I wonder if this means that it will only protect those neurons that have not yet died or if this drug could actually reverse some of the neuron damage caused by ALS. In any case, if it can help I sure hope that this drug's fast-track testing status pushes it through very soon!

 

[*ENV*]

My guess, in that the proposed target is mitochondrial support, is that it would only protect relatively healthy cells. There is another canDIDATE FROM Trophos (TRO19622 aka olesoxime) that seeks to plug the pores through which irritated mitochondria leak apoptotic factors into the cytoplasm. At some point this kind of support would be insufficient.

 

[BethU]

In my kindergarten-level understanding of all this: when neurons die, the muscles die, and the dead muscle tissue is disposed of by the body's scaverger cells (atrophy). Do the dead neurons remain in the brain? In order to reverse damage, wouldn't the neurons have to be "reborn/reactivated" in some way, and then brand new muscle tissue created?

I can see slowing progress by de-stressing live neurons, but something that would reverse it seems out of reach.

 

[*ENV*]

From my reading, the cytoskeleton remains forming the "scar" that is the "sclerosis" portion of ALS. Once the cell body dies a regenerative therapy (stem cells) would be necessary.

 

[BethU]

Aha! Thanks.

 

[Big Mike]

It would seem that it will take a types or types of stem cell and/or gene therapies to repair the damage and restore motor neurons and muscles cells/fibers. Drugs would be designed for slowing or stopping the disease process.

 

[Aleta]

I did not see this post earlier prior to submitting this response from Knopp in regards to compassionate use.

https://www.alsforums.com/forum/als-mnd-research-news/11048-no-compassionage-use-kns-760704-a.html

Aleta

 

[carrlos]

NOTE : They released this yesterday.

- They know now that the product is safe (for 9 months only, but I know people who would say it's good enough for them).
- They tell people that it is effective, and it looks like it has a real positive effect.

BRAVO but.. With this in mind, why no compassionate use?

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

Knopp Neurosciences Presents Further Encouraging Trends in its Phase 2 Study of KNS-760704 (Dexpramipexole) in ALS

Published April 18, 2010 Knowledge Center , PTC Member Leave a Comment
Tags: ALS, amyotrophic lateral sclerosis, Charcot's sclerosis, dexpramipexole, Knopp Neurosciences, KNS-760704, Lou Gehrig's desease, treatment of ALS

In an invited presentation today before the annual meeting of the American Academy of Neurology, Knopp Neurosciences Inc. (“Knopp”) described further encouraging trends observed in a previously reported Phase 2 study of KNS-760704 (dexpramipexole) in ALS.

Knopp reported that post hoc analyses showed a significant, dose-dependent trend of reduced treatment failure, as measured by both the ALS Functional Rating Scale-Revised (“ALSFRS-R”) and forced vital capacity, over the 12-week, placebo-controlled portion of the study.

In the case of ALSFRS-R, the number of treatment failures, defined as the loss of 6 points or greater in ALSFRS-R scores from baseline, totaled 9 subjects (or 33%), in the placebo group; 8 subjects (35%), in the 50 mg/day group, 4 subjects (15%) in the 150 mg/day group, and 2 subjects (8%) in the 300 mg/day group (p=0.014). In the case of pulmonary function, the number of treatment failures, defined as a reduction in forced vital capacity of 20% or greater from baseline, totaled 8 subjects (30%) in the placebo group, 3 subjects (13%) in the 50 mg group, 3 subjects (12%) in the 150 mg group, and 1 subject (4%) in the 300 mg group (p=0.028).

Knopp emphasized that these encouraging trends require confirmation in the large, long-term, controlled Phase 3 study setting necessary to establish that the drug is both safe and effective for ALS patients. Nevertheless, the additional analyses reported today were concordant with trends previously reported from Knopp’s Phase 2 study, which suggested the potential for dexpramipexole to improve outcomes in both function and survival.

“Despite the limited sample size and treatment periods, ongoing review of the Phase 2 data shows consistently encouraging trends in both pre-specified and post hoc analyses,” said Merit Cudkowicz, M.D., Professor of Neurology at the Massachusetts General Hospital of Harvard Medical School, who served as the principal investigator in the trial and who presented the Knopp study results by invitation at the Academy’s 2010 Clinical Trials Plenary Session. “We are eager to initiate Phase 3 studies as soon as protocol development and other arrangements are completed.”

As previously reported, the two-part Phase 2 study found that dexpramipexole met its primary objective in assessing its safety and tolerability in ALS patients for up to nine months. Secondary objectives included measuring the clinical effects of dexpramipexole on functional decline and mortality. The two-part design of the study provided the opportunity to assess the effects of the drug in the same sample of ALS subjects in two randomized, double-blind treatment periods separated by a one-month placebo washout.

In Part 1 of the study, 102 subjects received daily doses of 50 mg, 150 mg, or 300 mg of dexpramipexole or placebo for 12 weeks. As previously reported, dexpramipexole showed a dose-dependent trend in slowing the rate of disease progression as measured by the difference in slopes of the ALSFRS-R across treatment groups, with the greatest benefit observed in the 300 mg dose group.

In Part 2 of the study, 92 subjects were re-randomized to receive daily doses of 50 mg or 300 mg of dexpramipexole for 24 weeks. In addition to results again suggesting a dose-dependent trend in slowing the rate of disease progression as measured by the ALSFRS-R, there was also a trend toward a survival benefit in the 300 mg group compared with the 50 mg group. In an exploratory test comparing subject rankings on the basis of mortality and functional outcomes, subjects in the 300 mg group had a significantly improved outcome compared with the 50 mg group.

Knopp expects to initiate Phase 3 studies of dexpramipexole in ALS before the end of 2010.