CureDuchenne Founder’s Blog

As parents of a son with Duchenne muscular dystrophy, we feel blessed every day we spend with our sons.  It’s not every day, however, that we have reason to rejoice about the future.  Today is one of those days.  AVI Biopharma announced the top line results from their phase 2 trial for Eteplirsen, a drug which induces exon skipping in patients amenable to a skip of exon 51.

Chris Garabedian, CEO of AVI gave the the top line results which showed that after 24 weeks, four patients  on the 30 mg. dose had an average  increase of dystrophin of 22.5%.  The patients that had received the 50 mg. dose for 12 weeks did not show an increase in dystrophin, suggesting that duration of treatment is important.

I will always caution families, we still don’t know if exon skipping will actually become a real treatment for our sons with Duchenne, or to what extent it will help them.  On today’s conference call announcing these results, AVI’s chief medical officer, Ed Kaye, referred to “reasonable” dystrophin needed to function as 20%, so this study does indeed give us proof of concept and  hope that we might have a treatment sometime in the future.

Dr. Eric Hoffman at Children’s National Medical Center in Washington DC. spearheaded a collaboration with CNMC along with  the Foundation to Eradicate Duchenne and CureDuchenne several years ago.  This collaboration gave critical funding to AVI at a very crucial time which allowed them to move forward with the preclinical work neccessary to progress into this phase 2 human clinical trial.  Dr. Jerry Mendell and Dr. Kevin Flanigan at Nationwide Children’s Hospital in Columbus, OH, have played a pivotal role in conducting this trial over the last several months. We are very grateful to these investigators and organizations for their vision and dedication.

What Comes Next?

There’s a song named “Two Out Of Three Ain’t Bad.”  We now have reasonable data that suggests the drug is safe, there were no adverse events seen.  And, we know that the drug can produce dystophin, and at a reasonable amount.  Now, the big question is whether this quality/quantity of dystrophin will result in meaningful outcome measures and really help Duchenne patients live longer and healthier lives.

All patients including the placebo group  that were on the phase 2 are now on the open label extension study at either the 30 mg. or 50 mg. dose.  They will stay on this dose until they complete a total of 48 weeks dosing, at which time a biopsy will be taken and clinical outcome measures tested.  In the meantime, AVI will be actively involved with the FDA, compiling a brief and planning the pivotal phase 3 study.  Simutaneously, more animal studies will be conducted.  Since the FDA will most likely not accept the presence of dystrophin alone as justification to move forward with Eteplirsen, this extension phase and the data they gather will be very important.  The first patient to be dosed began in August of 2011, which would make this data available later this year.

As we await the clinical outcomes of the extension trial, AVI will be busy looking to the future, and CureDuchenne is equipped and ready to support their subsequent research on additional exons and next generation exon skipping compounds.  CureDuchenne will always fund research projects that show more immediate potential to help our Duchenne sons, such as already approved FDA drugs to slow the progression.  But, CureDuchenne will never take it’s eye off of the prize…to correct the actual defect that causes this terrible disease.  CureDuchenne is committed to fund research, like exon skipping, that will replace the missing dystrophin protein, while we fund more immediate research that could get FDA approved or off target drugs to keep our sons going in order to take advantage of these higer impact drugs.

CureDuchenne was also the first US organization to  support Prosensa, another exon skipping biotech company.  Prosensa was able to leverage our funds and received a committment of up to $650 million to develop their drugs and  is in the process of recruiting patients for their phase 3 pivotal trial.

Two out of three may not be bad, but it’s not enough.  So please join me as we rejoice in the possibility of an effective treatment, while at the same time show restraint with our expectations, since so many drugs do fail, even at late stage trials.  One thing is for sure…we will need all of you to support these research efforts…

TOGETHER, WE CAN CURE DUCHENNE!

If you would like to learn more about our exon skipping efforts, please call me at 949-872-2552

Debra Miller

 30mg dose raises dystrophin 22.5 pct in 24 weeks

* No improvement seen in clinical outcomes

By Deena Beasley

April 2 (Reuters) – A small trial of U.S.-based AVI BioPharma Inc’s experimental muscular dystrophy drug met its goal of increasing levels of a key protein, but did not demonstrate that the drug had an impact on walking ability or other clinical endpoints.

The mid-stage trial, or Phase IIb, which involved 12 boys with Duchenne muscular dystrophy, found that the four patients treated for 24 weeks with a 30 mg dose of the drug, eteplirsen, had a 22.5 percent average increase in levels of dystrophin, a protein essential to building muscle, compared to no increase for four patients treated with a placebo.

Duchenne muscular dystrophy — a muscle degeneration disease affecting young children, almost exclusively boys — leads to paralysis and death in young adulthood. At least 250,000 people worldwide are believed to be afflicted with the disease.

Eteplirsen is designed to silence a specific strand of RNA so that the body can produce the dystrophin that people with Duchenne muscular dystrophy are unable to produce.

The trial found that the four patients treated for 12 weeks with a 50 mg dose of the drug did not show a significant increase in dystrophin, suggesting that a longer duration of dosing is needed.

It also found no significant improvements in clinical outcomes, including a six-minute walk test, in the treated groups compared to placebo.

“We anticipate that these levels of dystrophin could lead to significant clinical benefit if maintained over a longer course of treatment,” Dr. Jerry

Mendell, director of the Centers for Gene Therapy and Muscular Dystrophy at Nationwide Children’s Hospital in Columbus, Ohio and the study’s lead investigator, said in a statement.

There were no treatment-related adverse events, no serious side effects, and no evidence of kidney toxicity.

AVI BioPharma Chief Executive Officer Chris Garabedian said the company plans to discuss with U.S. regulators how best to conduct a longer pivotal trial of the drug.

“The hope is that if we can delay or halt the progression of the disease we would be able to avoid these kids ending up in a wheelchair,” he said. “It would avoid the need for ventilators, maybe even prevent death.”

Eteplirsen is designed to skip a specific “exon,” or protein-coding sequence of the dystrophin gene that is mutated in about 15 percent of people with Duchenne muscular dystrophy.

AVI BioPharma is also developing drugs targeting other exon mutations responsible for muscular dystrophy.

Garabedian said he would prefer raising funding for a pivotal trial from capital markets, rather than a partnership.

“In the rare disease area, it doesn’t take a large commercial infrastructure to do this,” he said.

BOTHELL, WA–(Marketwire – March 30, 2012) – AVI BioPharma, Inc. (NASDAQ: AVII),  a developer of RNA-based therapeutics, today announced it will hold a conference call at 8:00 a.m.  EDT (5:00 a.m. PDT) on Monday, April 2, 2012 to discuss top-line results from its Phase IIb study evaluating eteplirsen for the treatment of Duchenne Muscular Dystrophy (DMD).                                                                          

The conference call may be accessed by dialing 800.561.2718 for domestic callers and 617.614.3525 for international callers. The passcode for the call is 99858553. Please specify to the operator that you would like to join the “AVI BioPharma Phase IIb Top-Line Data Results Call.” The conference call will be webcast live under the events section of AVI’s website at www.avibio.com and will be archived there following the call for 90 days. Please connect to AVI’s website several minutes prior to the start of the broadcast to ensure adequate time for any software download that may be necessary.

About AVI BioPharma
AVI BioPharma is focused on the discovery and development of novel RNA-based therapeutics for rare and infectious diseases, as well as other select disease targets. Applying pioneering technologies developed and optimized by AVI, the Company is able to target a broad range of diseases and disorders through distinct RNA-based mechanisms of action. Unlike other RNA-based approaches, AVI’s technologies can be used to directly target both messenger RNA (mRNA) and precursor messenger RNA (pre-mRNA) to either down-regulate (inhibit) or up-regulate (promote) the expression of targeted genes or proteins. By leveraging a highly differentiated RNA-based technology platform, AVI has built a pipeline of potentially transformative therapeutic agents, including eteplirsen, which is in clinical development for the treatment of Duchenne muscular dystrophy, and multiple drug candidates that are in clinical development for the treatment of infectious diseases. For more information, visit www.avibio.com.
AVI Investor and Media Contact:
Erin Cox
425.354.5140
ecox@avibio.com

AVI Media Contact:
David Schull
858.717.2310 or 212.845.4271
David.Schull@russopartnersllc.com

All of us at Cure Duchenne are so grateful to our supporters who are spreading the word about Duchenne!                                                                                      Duchenne muscular dystrophy is the most common muscle disease in children.  One if 3500 boys will be  born with this disease, it knows no ethnic, geographical or economic boundaries.

This disease can be cured and there are treatments that are in development that can save these children.  But, this disease is too big for the families of Duchenne boys to conquer on their own.  We need the support of everyone who cares about children to help us win this battle with Duchenne.

Please send this video (http://www.youtube.com/watch?v=4JVGIZB3FO0) to your contacts and Facebook friends and encourage them to send it on.  Use the image on this page as your Facebook  timeline banner and ask your friends to donate $10 on their cell phone by texting “SAVE” to 80888.

Please, help our children that suffer from Duchenne.

“TOGETHER, WE CAN CURE DUCHENNE!”

In parallel to the on-going development of the lead compound PRO051/GSK2402968, which is being developed by GSK with an active involvement of Prosensa, there are five more compounds for Duchenne in Prosensa’s pipeline.  Below you can find an update about the current state of development of these compounds.

Prosensa is currently conducting a clinical study to investigate the effect of PRO044 in boys with Duchenne muscular dystrophy, who have a dystrophin gene mutation amenable to an exon 44 skip. This study is a phase I/IIa study that will assess the safety, tolerability, efficacy and pharmacokinetics of PRO044. The inclusion/exclusion criteria, as well as the endpoints and investigator locations are available on www.clinicaltrials.gov (search terms ‘Duchenne and Prosensa’ or ‘PRO044’).

Prosensa has four additional compounds in development that target exons 45, 53, 52 and 55 (PRO045, PRO053, PRO052 and PRO055). These programs currently are in the pre-clinical development phase. It is anticipated that the company will be able to progress PRO045 and PRO053 into the clinic in the second half of 2012. Discussions are on-going with the regulatory authorities to ensure optimum development. Each trial will be posted at the website www.clinicaltrials.govas soon as the study design is finalized and all the required approvals of authorities and ethics committees are granted.

It is always difficult to predict timelines for drug development. Therefore, please keep in mind that expected start and end dates are based on predictions and could be delayed if unforeseen events occur.

Prosensa is very committed to developing safe and effective treatments and we will do our utmost to succeed herein. Our goal is to develop compounds for as many patients as feasible who may benefit from the exon skipping platform.

Click To View Documents: FAST Sign-on Letter.docx (12KB);                                                                      

From the EveryLife Foundation:

We are very excited to share the news that rare disease Accelerated Approval language made it into the House draft PDUFA bill.  The language that incorporates the goals of ULTRA (shown below) is the only mention of rare diseases in the entire 205-page bill.  This is a huge accomplishment for the rare disease community and is a major step toward spurring the development of lifesaving treatments.

Please help us build on this great success by taking two quick actions to support the FAST Act that includes the rare disease language below.  The more support we have for the FAST Act, the better positioned we will be to keep our language in PDUFA:

1)      Please add your organization’s name to the FAST support sign-on letter (attached) by emailing Emily Roberts at BIO at eroberts@bio.org by Wednesday March 21^st

2)      Click here to email your Member of Congress and ask him/her to become a Co-Sponsor of FAST

We would not have reached this huge milestone without the support and hard work of the rare disease community.  The more than 140 patient organizations and the 2700 advocates who took action to support ULTRA are the real champions of this achievement.

Below is the language from ULTRA/FAST that was incorporated into PDUFA:

Under Subtitle D – Accelerated Approval,  Page 186, line 16:
“(taking into account the severity or rarity of the disease or condition and the availability of alternative treatments) that the product has an effect on—
(A) a surrogate endpoint that is reasonably likely to predict clinical benefit; or
(B) a clinical endpoint, including an endpoint that can be measured earlier than irreversible morbidity or mortality, that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit.
The evidence to support that an endpoint is reasonably likely to predict clinical benefit may include epidemiological, pathophysiologic, pharmacologic, therapeutic or other evidence developed using, for example, biomarkers, or other scientific methods or tools.”

Page 191 line 3: “Considerations. – In developing the guidance . . . . the Secretary shall consider . . . . for drugs designated for a rare disease or condition under section 526 of the Federal, Food, Drug, and Cosmetic Act; and
(2)how to incorporate novel approaches to the review of surrogate endpoints based on pathophysiologic and pharmacologic evidence in such guidance, especially in instances where the low prevalence of a disease renders the existence or collection of other types of data unlikely or impractical.”

The EveryLife Foundation believes the above language will empower the FDA to consider achievable scientific evidence to qualify a surrogate endpoint for use in a clinical trial, giving very rare diseases that have never been treated before an opportunity to use the Accelerated Approval process.  Most importantly, the inclusion of the language is a message from Congress to the FDA, that they should allow rare diseases as well as other life-threatening diseases access to the Accelerated Approval pathway.  Additionally, the guidance that the FDA is required to publish within one year of passing PDUFA will lay out a predictable and achievable regulatory process that will encourage investors and industry to fund the development of treatments very rare diseases.

More Information:

Inside Health Policy – Draft Energy & Commerce Bill Reveals FDA Reform Priorities For User Fee Package

Emil’s Blog – Guest blogger Julia Jenkins explains how ULTRA became FAST and what happens next

Newport beach, ca, MARCH 14, 2012:  Eight-year-old Tyler Armstrong, of Yorba Linda, Calif., has set his sights on becoming one of the youngest ever to summit one of the highest mountains in the world, Mt. Kilimanjaro. He already set a record as the youngest person to climb Mt. Whitney in a single day – the highest peak in the contiguous United States. Showing remarkable compassion, Tyler decided he would climb Mt. Kilimanjaro not for himself, but for the 300,000 boys worldwide who suffer from Duchenne muscular dystrophy and for his friend 12-year-old Suhail Zaveri of Anaheim. So, today, Tyler, along with a group of others, announced they will climb Mt. Kilimanjaro June 23 – July 2, 2012 to raise money and awareness for CureDuchenne.

As the most common and lethal form of muscular dystrophy, Duchenne impacts one in 3,500 boys. Boys with Duchenne are usually diagnosed by the age of 5, in a wheelchair by age 12 and most don’t survive their mid-20s. “I am doing this climb to help Suhail and other boys my age that have Duchenne because most of them have a hard time even walking,” said Tyler.

CureDuchenne (CureDuchenne.org) is a nonprofit organization dedicated to funding research to find treatments, and ultimately a cure, so that this generation of Duchenne boys can be saved. Tyler’s climb is being coordinated through CureDuchenne, as part of the fourth annual Climb to CureDuchenne Pick Your Peak event. If everything goes as planned, Tyler, due to special permission granted by the Tanzanian government, will be the second youngest to reach the 19,341 foot summit of Mt. Kilimanjaro and the youngest person to lead a fundraiser of this caliber for the nonprofit.

Achieving this impressive athletic goal requires a dedicated family, impressive athletic ability, a strict training regiment including four-mile runs coupled with an intensive training climb schedule. Achieving this compassionate goal requires a heart-felt want to help others who cannot do what he can. Along with CureDuchenne, Tyler is showing the world what can be done when anyone (even 8-year-olds) put their minds and bodies to it.

“Boys with Duchenne, Tyler, and CureDuchenne all seem to have one thing in common – determination,” said Debra Miller, founder and CEO of CureDuchenne. “We are thrilled Tyler decided to climb Mt. Kilimanjaro to help find a cure for Duchenne muscular dystrophy on behalf of the Duchenne boys who can’t.”

Others can participate in Climb to CureDuchenne Pick Your Peak by choosing any mountain, hill or tall building to climb on June 23 or June 30, 2012. Anyone, regardless of athletic ability, is encouraged to participate individually or to form a team and secure sponsors/contributors to raise funds to find a cure for Duchenne. Click here to donate to the climb. To learn more about Tyler visit TopWithTyler.com.

Travel Dirty is the official travel sponsor for the Mt. Kilimanjaro climb. The international travel agency caters to those who want their vacations to include both stunning locations and athletic adventures.

About CureDuchenne
CureDuchenne is a national nonprofit organization located in Newport Beach, Calif. dedicated to finding a cure for Duchenne, the most common and most lethal form of muscular dystrophy. As the leading genetic killer of young boys, Duchenne affects more than 300,000 boys worldwide.

 CureDuchenne has garnered international attention for its efforts to raise funds and awareness for Duchenne. With the help of CureDuchenne’s distinguished international panel of Scientific Advisors, funds raised by CureDuchenne support the most promising research aimed at treating and curing Duchenne. To date, seven CureDuchenne research projects have made their way into human clinical trials – a unique accomplishment as few health-related nonprofits have been successful in being a catalyst for human clinical trials.

Many fathers of Duchenne sons are working full time to support their families, and then working full time to support their son’s health and physical limitations.  I know there are many dad’s like me who would like to connect and talk about what works for us and learn what works for others in balancing the needs of our sons with Duchenne with our entire family.

As parents, we put our children first and are constantly looking for positive ways to improve the lives of our families.  Whether it be searching for or creating activities that our sons can participate in, improving our son’s health through physical therapy and nutrition, increasing our strength and endurance so we will be equipped to deal with the demands of a weakening child, keeping up to date on research and finding ways to support research projects, sharing how faith plays a role in coping with this disease, and most of all…finding ways for our sons to have fun.

Here’s my story and I look forward to hearing your story and finding out what works for you and your son.  Please contact me or send a friend request to me at:  https://www.facebook.com/#!/pfmiller.  I’ll include you in our Facebook group and I look forward to getting to know you.

The morning of November 16, 2002, we received a phone call from our son’s pediatrician confirming that our only child has Duchenne muscular dystrophy.

Six years earlier, my wife Debra and I were preparing for the arrival of our son, Hawken. As first time parents, Debra and I enjoyed our time together talking about all the things we would do as a family.  All the things we would teach our son.  Those special times seem like a completely different lifetime.  All those hopes and dreams were crushed on November 16, 2002.

We had to adjust and rebuild our hopes and dreams.  We were and still are committed to not letting Duchenne rob us of joy in our lives.  I loved being a Dad from the moment our son entered the world.  In fact, it is my most favorite thing to be!   “Daddy hold you” is an early memory I will hold onto forever.  I relish every request to fix something, play something, answer a question and do something.

Initially, that fateful day in November, caused me to think that much of what I had to offer as a Father was diminished.  The opportunity to play catch, do other physical activities together and coaching sports were lost.  Although, there have been adjustments, I have found where one door has closed, others have opened.  I am constantly coming up with solutions and work arounds to be able to participate and do as many things as possible together.  In other words, I get to fix things so that they work.

These solutions are by no means able to eliminate the challenges of life with Duchenne for my son; however they present opportunities to experience father and son adventures.  We have found ways to be involved and participate.  My son knows that if there is something he wants to do, there is a will and we will find a way.  I think that’s what dads do!

We have been executing this strategy ever since November 16, 2002.  It is not always successful, but what is?  Our adventures and life lessons for my son are numerous.

We are fast approaching ten years of life with Duchenne.  Yes, I have my moments of grief, but I am a dad that relishes every moment and gives it my all for my son.  The adversity isn’t going away anytime soon, but neither is the commitment to joy and adventure.

No one really knows what the future holds, but what I do know is that I will be the dad my son needs me to be.

I am a Duchenne Dad!

Paul Miller

Cure Duchenne will host its third annual “Breakfast with the Experts” at the Duchenne Scientific Summit on February 11^th at the Balboa Bay Club in Newport Beach, CA.  The meeting will be broadcast via a worldwide webcast.  You will be able to submit questions online.

Visit www.ustream.tv/channel/cd2012 on February 11th, between 8:00am – 12:30pm Pacific Standard Time. Our webcast should load automatically.

If you have a question you’d like to submit prior to the meeting, please send them to debra@cureduchenne.org.

We appreciate the support of our conference sponsor, Allergan Foundation.

TOGETHER, WE CAN CURE DUCHENNE!

Scheduled speakers:

Barry J. Byrne, M.D., Ph.D.

Professor and Associate Chair of Pediatrics,

Molecular Genetics & Microbiology

Director, Powell Gene Therapy Center

University of Florida, School of Medicine

Kevin P. Campbell, Ph.D.

Investigator, Howard Hughes Medical Institute

Director, Senator Paul D. Wellstone MDCRC

University of Iowa, Carver College of Medicine

Jeffrey Chamberlain, Ph.D.

Principal Investigator, Chamberlain Lab,

Department of Neurology, University of

Washington School of Medicine

Eric Hoffman, Ph.D.

Director, Research Center for Genetic Medicine

George Washington School of Medicine and

Health Sciences

Children’s National Medical Center

Washington DC

Edward Michael Kaye, M.D.

Senior Vice President and Chief Medical Officer

AVI BioPharma

Douglas Macdonald, Ph.D.

Director, Drug Discovery

CHDI Management, Inc.

M. Carrie Miceli, Ph.D.

Professor

Department of MIMG

David Geffen School of Medicine at UCLA

and UCLA College of Letters and Sciences

Stanley F. Nelson, M.D.

Professor

Departments of Human Genetics

David Geffen School of Medicine at UCLA

Pier Lorenzo Puri, MD Ph.D

Associate Professor, Muscle Development and

Regeneration Program

Sanford-Burnham Medical Research Institute,

La Jolla, CA – US

Bill Abernathy

the VP of Global Market Development

Prosensa

Justin Fallon, Ph.D.

Brown University

Ron Victor, M.D.

Cedars Sinai Hospital