Dr. Susan Perlman, one of the two investigators for the phase III trial in the United States, said, "I still strongly support the disease-modifying effect of Catena® in Friedreich's Ataxia. I believe it slows the progression of the neurological and cardiac aspects of this condition over time, and I strongly recommend that patients continue in the open-label extension study arm of the Phase III IONIA trial to enable us to gather as much longer term data as possible."  In its published statement and its public telephone conference earlier today, Santhera emphasized that the trial results “have not dampened our confidence in the drug's potential in Friedreich's Ataxia.”  Santhera goes on to say that it is hopeful that additional data from the “extension study” in the United States (in which all patients who participated in the U.S. phase III trial will now receive Idebenone if they choose to continue) and from the European phase III trial in which “results are expected in the first half of 2010,” will be sufficient to achieve statistical significance and provide the basis for filing for approval in the United States and Europe.

Now, in my own words, let me say what I believe this all means to all of us.  First and foremost, let me say, on behalf of every FA patient and patient family, thank you from the bottom of our hearts to all patients and patient families who participated and continue to participate in this phase III clinical trial of Idebenone as a potential treatment for FA.  As with all clinical trials, the FA community will learn a great deal from this trial.  We will learn a great deal about FA, about how to measure progress in FA and how best to conduct clinical trials in FA.  In sum, we will take important steps toward our goal of curing this disease.  None of that would be possible without the many eligible patients and families who stepped forward and made the sacrifices required to participate in this trial.  We are all grateful to you and, like Dr. Susan Perlman, strongly encourage you to continue your all-important contribution to our mutual cause by participating in the “extension study” so that additional data can be added to the results of the U.S. and European trials so even more can be learned and the required “statistical significance” can be achieved.

So, there is still much to be done to obtain the most positive outcome possible regarding Idebenone.  Although Idebenone continues to be shown to be safe and well tolerated, it is clear that the results of the U.S. phase III trial were not nearly as positive as most of us hoped and expected.  We had received indications that, if the phase III trial of Idebenone reproduced the results observed in the phase II trial at NIH, the FDA would be likely to approve the drug for FA.  But, the trial fell short of that goal in the following ways and for the following reasons:


   The U.S. phase III trial showed improvements in those receiving drug but those improvements were about half as large as observed in the phase II trial at the NIH. 

   The “effect size” (difference between any improvements in those taking drug and the results observed in those taking placebo) was further reduced by the amount of improvement in those taking placebo.  In other words, those taking drug improved more than those taking placebo but the difference between the two was less than expected and did not reach the threshold of statistical significance.

  All of us expected the benefits of Idebenone to be modest, so none of us was expecting a huge “effect size.”  Had the trial been longer, the “effect size” could have been expected to have been greater because the “placebo effect” usually diminishes over time and the improvements in those taking drug could be expected to become more apparent along with FA’s slow progression among those taking placebo.  Similarly, a trial with more patients would be better able to measure small differences between those taking drug and those taking placebo.  So, the “extension study” in the United States and the European trial offer opportunities to collect data more convincing for the FDA, European and Canadian regulators.  


To expand a bit on the importance of the European trial, it is, when compared to the U.S. trial, longer (one year vs. 6 months), larger (232 patients vs. 70) and includes mostly adults (the U.S. trial involved 8-17 year-olds).  Santhera expects the results of the European trial during the first half of 2010 and those results could possibly show sufficient “effect size,” especially when added to data from the open-label U.S. “extension study,” to proceed with submitting the net results to the FDA for approval.

Another way to summarize what has just happened is as follows:

Based on the positive results of the earlier trials and research of Idebenone in FA, on the natural history available regarding FA patients and on the suggestions of the FDA, Santhera judged that a phase III trial of Idebenone could be conducted successfully in 70 patients over a six-month period.  However, given all the variables -- for example, the differences among FA patients (heterogeneity), FA’s slow progression, the placebo effect (not uncommon in clinical trials), and clinical outcome measures that are always less than perfect -- this trial by itself did not result in data good enough to obtain approval of the drug.  We need to proceed with the U.S. “extension study” and the European trial and see if the resulting data crosses the threshold for approval.

So, we are obviously disappointed.  We had hoped that the U.S. trial would be sufficiently successful to lead to prompt approval of Idebenone as a treatment for FA.

But, we are not daunted.  Our patient community will rise to the challenge and complete the “extension study” and the European trial in search of additional, compelling data.  Our scientific community will learn a great deal from these and subsequent trials.  We know that mitochondrial dysfunction plays a key role in FA and that Idebenone and other compounds in our pipeline represent a valid and promising pathway to effective treatment.  We know we are extremely fortunate, especially as a rare disease group, to have such a motivated, united patient family community, such a talented and devoted scientific community, such generous supporters, and so many pharmaceutical companies advancing our cause.  We will all continue to work together and will not fail.  We will treat and cure FA.

Warm regards,

----- Original Message -----
From: Ron Bartek
To: FAPG ; This email address is being protected from spambots. You need JavaScript enabled to view it.
Sent: Tuesday, May 19, 2009 11:04 PM
Subject: [internaf] Re: ENG: Santhera Press release - Santhera's US Phase III IONIA Trial in Friedreich's Ataxia Misses Primary Endpoint

Ronald J. Bartek
Friedreich's Ataxia Research Alliance (FARA)
P. O. Box 1537
Springfield, VA 22151
Tel (703) 426-1576
FARA website: http://www.CureFA.org
Email: This email address is being protected from spambots. You need JavaScript enabled to view it.
Please register in the FARA Patient Registry at http://www.curefa.org/registry/ and for e-news at http://visitor.constantcontact.com/email.jsp?m=1101190303489

The legacy of Marie Schlau: literature to help cure Friedreich's Ataxia

If you feel like reading an unputdownable novel while collaborating with a just and solidary cause, "The Legacy of Marie Schlau" is your book! 100% of all funds raised will be dedicated to medical research to find a cure for Friedreich's Ataxia, a neurodegenerative disease that affects mostly young people, shortening their life expectancy and confining them to a wheelchair.

The life of Marie Schlau, a German Jewish girl born in 1833 hides great unsolved mysteries: accidents, disappearances, enigmas, unknown diagnoses, disturbing murders, love, tenderness, greed, lies, death ... alternatively a different story unfolds every time and takes us closer to the present. Thus, there are two parallel stories unravelling, each in a different age and place, which surprisingly converge in a revelatory chapter.

Paperback and Kindle versions for "The legacy of Marie Schlau" available for sale at Amazon now!



Research projects currently being financed by BabelFAmily

Currently, BabelFAmily is financing two promising research projects aimed at finding a cure for Friedreich's Ataxia. Whenever you make a donation to us or purchase a copy of "The legacy of Marie Schlau", this is where all funds raised will be devoted to:

1) Gene Therapy for Friedreich's Ataxia research project:


The project is the result of an initiative of Spanish people affected by this rare disease who are grouped in GENEFA in collaboration with the Spanish Federation of Ataxias and the BabelFAmily. The Friedreich’s Ataxia Research Alliance (FARA), one of the main patients’ associations in the United States now joins the endeavour.

2) Frataxin delivery research project:

The associations of patients and families Babel Family and the Asociación Granadina de la Ataxia de Friedreich (ASOGAF) channel 80,000 euros of their donations (50% from each organisation) into a new 18-month project at the Institute for Research in Biomedicine (IRB Barcelona). The project specifically aims to complete a step necessary in order to move towards a future frataxin replacement therapy for the brain, where the reduction of this protein causes the most damage in patients with Friedreich’s Ataxia.

The study is headed by Ernest Giralt, head of the Peptides and Proteins Lab, who has many years of experience and is a recognised expert in peptide chemistry and new systems of through which to delivery drugs to the brain, such as peptide shuttles—molecules that have the capacity to carry the drug across the barrier that surrounds and protects the brain. Since the lab started its relation with these patients’ associations in 2013*, it has been developing another two projects into Friedrich’s Ataxia.



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