Creating Hope Act 2010 Bill Would Extend Priority Review Voucher System To Rare Pediatric Diseases
August 9, 2010 by Carrie
Filed under Bloggin' Mama, Legislation
** By Chris Hempel
Great news for the pediatric rare disease community came out late last week — rare disease advocates please get this out on your blogs!
Senators Sam Brownback (R-KS), Sherrod Brown (D-OH), and Al Franken (D-MN) are supporting the bipartisan bill S. 3697, the “Creating Hope Act of 2010.” Nancy Goodman, Executive Director of Kids v Cancer, is the person leading the charge on S. 3697 and a priority review voucher system for pediatric rare diseases.
In 2009, Nancy lost her son Jacob to a rare pediatric cancer called medulloblastoma. She is an inspiration to all in the rare disease community!
The Creating Hope Act of 2010 builds upon the Food and Drug Administration Amendments Act of 2007, often called the “treat and trade” program, which established a priority review voucher program for drugs or biologics targeting neglected tropical diseases. At the time this bill was passed, rare childhood diseases were excluded.
he Creating Hope Act of 2010 will encourage the creation of new drugs for underserved children like Addi and Cassi who suffer from serious and life threatening medical conditions by providing a priority review voucher (PRV) as an incentive to pharmaceutical companies who develop drugs for rare pediatric diseases like Niemann Pick Type C.
This is exactly the type of novel incentive system I have been asking for that could fast track cyclodextrin research. For example, with a PRV system in place, I could get a company like Johnson and Johnson to actually take on Niemann Pick Type C disease research and help me make a cyclodextrin drug for Niemann Pick Type C kids. In turn, Johnson and Johnson could receive a priority review voucher that gives them priority FDA review of another application that would otherwise be reviewed under FDA’s standard review clock.
This priority review voucher could be used for a blockbuster drug that a company would want want to bring to market and receiving priority review could mean millions of dollars to a Pharma or biotech company. This is why they would be willing to invest in Niemann Pick Type C research and cyclodextrin and help our small community bring a potentially life saving compound to market for kids like Addi and Cassi.
Since I already have an orphan drug application filed and approved with the FDA, having a priority review voucher system in place potentially makes Niemann Pick Type C an attract investment risk by Pharmas or BioTechs.
Priority reviews vouchers for pediatric rare diseases are a win-win for everyone! We need to rally the rare disease community to fight for the passing of S. 3697, Creating Hope Act 2010 bill.
Below are some key provisions of the S. 3697, Creating Hope Act 2010 bill:
- Extension to pediatric rare diseases: This legislation includes rare pediatric disease within the scope of the program. This category encompasses any disease that is “rare” within the meaning of the Orphan Drug Act (affects less than 200,000 people, or the cost of development would exceed revenue) is recognized in the medical community as affecting a pediatric population and is a new drug that has not received FDA approval for an adult indication
- Closing a loophole: This legislation would prevent companies from receiving a voucher for tropical disease products that they already market in other countries. This change will ensure that the program rewards only innovative treatments
- Unlimited transferability of vouchers: A voucher may now be transferred unlimited times provided that the transferee, in each instance of transfer, notifies the FDA of the change in ownership. This change enables drug companies to maximize the value of the voucher in the marketplace
- Optional upfront priority review designation process: Under the current law, sponsors do not know whether their new drug application will qualify for a voucher until the time of FDA approval. The proposed legislation permits sponsors of both tropical disease drugs and rare pediatric disease drugs to seek a designation that the new drug would qualify for a voucher, should it be approved, even before they submit their new drug application.
- Adds Chagas disease to the list of neglected tropical diseases: Chagas disease is responsible for more deaths in Central and South America than every other parasite-borne disease, including malaria. Yet, despite its profound impact, research and development of new treatments is severely underfunded. The addition of Chagas to the list of eligible diseases fulfills the intent of the original authors.
- Reporting and marketing requirements: The Creating Hope Act requires that the sponsor submit a statement of good faith intent to market the eligible drug, as well as a report describing the demand and distribution of the ultimate product.
The Scientist Magazine: A Rare Chance
February 3, 2010 by Mommy
Filed under Bloggin' Mama, Parkinson's Link, Pics and Videos
http://www.the-scientist.com/article/display/57100/By Alison McCook
A rare chance
Over the course of 5 days last summer, an army of researchers and clinicians examined, poked, and prodded 1-year-old Hannah Ostrea at the National Institutes of Health (NIH). Experts in neurology, rehabilitation medicine, physical therapy, speech pathology, and anesthesiology gave the little girl an EEG, a test of her heart’s electrical activity (EKG), an MRI, a CT scan, X-rays, and a throat exam (laryngoscopy). All this testing was meant not only to help Hannah but in the hope that her rare disease could reveal something about another condition that affects 1 million Americans: Parkinson’s.
Hannah has Gaucher’s disease, and within hours of her birth, it was obvious something was wrong. Looking past her thick head of dark hair, and the fact that she could down an entire bottle of formula in 5 minutes, clinicians quickly saw that her spleen was massive, and her platelet counts were rock bottom. Her liver was expanding—in a few months it looked like she had a volleyball in her stomach. These are the classic signs of Gaucher’s, a rare, recessive genetic disorder in which the body does not produce enough of a lysosomal enzyme that breaks down the fatty substance glucocerebroside, causing it to glob up in cells of the liver, spleen, and other organs—including, sometimes, the brain.
But researchers have never seen the combination of mutations Hannah carries, so doctors couldn’t determine if she had the Type 2 or Type 3 form. Children with Type 2 typically die before their third birthdays, while those with Type 3 can live much longer. “They [wouldn’t] give us a prognosis,” Hannah’s mom, Carrie Ostrea, says. “They came out and said that to us. Which is fine by me.”Hannah has many classic Gaucher’s symptoms, such as developmental delays, and the inability to easily shift her eyes from side to side or up and down. But she also has some puzzling symptoms. For one, she only blinks once every 30 minutes or so—“you’ll have a staring contest with her,” Ostrea laughs. This is not a symptom of Gaucher’s disease, but it is a symptom of Parkinson’s.
Indeed, in recent years, researchers have been noting more and more crossover between the two diseases, and the hope is that insights into one will reveal secrets of the other.
In an October issue of the New England Journal of Medicine, Ellen Sidransky at the NIH and her colleagues found that Parkinson’s patients were five times more likely to carry a mutation in the gene associated with Gaucher’s disease. Furthermore, Parkinson’s patients with the mutation in the Gaucher’s gene tended to develop Parkinson’s earlier, and were more likely to have family members with Parkinson’s (N Engl J Med, 361:1651–61, 2009). It’s unknown how many people have signs of both diseases, Sidransky notes, but it’s “clearly dozens and dozens.”
Still, Parkinson’s and Gaucher’s are more different than they are alike. One comes from a deficiency of the lysosomal enzyme that breaks down glucocerebroside, the other likely from a deficiency of dopamine, and it’s largely unclear why the two diseases are linked, says Sidransky. Perhaps the lysosome plays a role in Parkinson’s; the protein misfolding that underlies Parkinson’s may be aggravated by mutations in the Gaucher’s gene.
Gaucher’s itself is an interesting model for trying to understand single-gene diseases, Sidransky adds. She and her colleagues like to invite patients with rare presentations of a disease to the NIH to study them and hopefully learn something about an entirely different condition. “I’ve always been convinced that focusing on one thing and becoming an expert helps you see connections” between that one question you’re investigating and other unanswered—perhaps even more significant—questions.
The NIH visits can be long, but Hannah held up fairly well, her mother says. She didn’t like waking up from the EEG and being tied down, and didn’t like the heart ultrasound, but the neuro-ophthalmologist got her to laugh hysterically by turning his video camera around so she could look at herself. “She just thought that was the funniest thing in the world,” Ostrea says.
Genzyme to Evaluate to-BBB’s Technology for Delivering Biologics to the Brain
November 6, 2009 by Mommy
Filed under Bloggin' Mama, Gaucher's - News
This could be HUGE!!! I’m waiting to hear back from Genzyme to get more details — Cerezyme, Genzyme’s product, delivered to the brain! That could be what we have been waiting for!!!!
http://www.genengnews.com/news/bnitem.aspx?name=67331403
Nov 3 2009, 11:02 AM EST
Genzyme to Evaluate to-BBB’s Technology for Delivering Biologics to the Brain
GEN News Highlights
Genzyme and Netherlands-based to-BBB established a research collaboration to evaluate the use of the latter’s G-Technology™ to transport biologics against neurodegenerative diseases across the blood brain barrier (BBB).
G-Technology has been developed to transport different classes of drugs directly across this barrier using glutathione-coated liposomes. The company’s research partnership with Genzyme follows on from a similar agreement with MedImmune, signed in September.
Liposomal formulation allows the encapsulation of a wide range of compounds and biological molecules without changing their function and protecting them against degradation and immune responses, according to to-BBB. Coating liposomes with PEG further ensures a prolonged circulation time in plasma. Conjugation of glutathione to the tips of the PEG molecules targets the liposomes toward the active glutathione transporters on the blood-brain barrier, the firm explains.
to-BBB’s lead in-house project is 2B3-101, a G-Technology formulated doxorubicin, currently in preclinical development. A Phase I/II trial is expected to start during the second half of 2010. Additional preclinical-stage in-house projects are ongoing in diseases including Alzheimer’s and lysosomal storage diseases.
The Parkinson’s Disease – Gaucher Disease link
October 23, 2009 by Mommy
Filed under Bloggin' Mama, Gaucher's - News, Parkinson's Link
What we have known for a few months has finally started hitting the mainstream media now as well as some other medical sites. There are just a few….
Question is, now how can we capitalize on this and get the Parkinson’s community to start paying attention to our Gaucher kids?
Gaucher disease linked to Parkinson’s – Los Angeles Times
Mutant Gene Raises Risk of Parkinson’s (WebMD)
Glucocerebrosidase Mutations in Parkinson’s Disease New England Journal of Medicine (subscription)
Study Conclusively Ties Rare Disease Gene To Parkinson’s – Medical News Today
A possible delivery system that crosses the blood-brain barrier!!!!
September 22, 2009 by Mommy
Filed under Bloggin' Mama, Gaucher's - Research
Kyle’s mom and I are off to get the researchers’ opinions of this hopeful breakthrough!
University of Iowa scientists use blood-brain barrier as therapy delivery system
Enzyme delivered through the bloodstream corrects deficiencies in the brain
The blood brain barrier is generally considered an obstacle to delivering therapies from the bloodstream to the brain. However, University of Iowa researchers have discovered a way to turn the blood vessels surrounding brain cells into a production and delivery system for getting therapeutic molecules directly into brain cells.
Working with animal models of a group of fatal neurological disorders called lysosomal storage diseases, the UI team found that these diseases cause unique and disease-specific alterations to the blood vessels of the blood brain barrier. The scientists used these distinct alterations to target the brain with gene therapy, which reversed the neurological damage caused by the diseases.
The findings, which were published Sept. 13 in Nature Medicine’s Advance Online Publication (AOP), could lead to a new non-invasive approach for treating neurological damage caused by lysosomal storage diseases.
“This is the first time an enzyme delivered through the bloodstream has corrected deficiencies in the brain,” said lead investigator Beverly Davidson, Ph.D., UI professor of internal medicine, neurology, and molecular physiology and biophysics. “This provides a real opportunity to deliver enzyme therapy without surgically entering the brain to treat lysosomal storage diseases.
“In addition, we have discovered that these neurological diseases affect not just the brain cells that we often focus on, but also the blood vessels throughout the brain. We have taken advantage of that finding to delivery gene therapy, but we also can use this knowledge to better understand how the diseases impact other cell types such as neurons,” she added.
Lysosomal storage diseases are individually quite rare, but as a group they affect approximately 1 in 8,000 live births. The diseases are caused by deficiencies in enzymes that break down larger molecules. Without these enzymes, the large molecules accumulate inside cells and cause cell damage and destruction.
Enzyme replacement therapy has been successful in treating one form of lysosomal storage disease called Gaucher disease. However, storage diseases that affect the central nervous system remain untreatable because it has not been possible, to this point, to get the missing enzymes past the blood-brain-barrier and into the brain.
“Our discovery allowed us to test the idea that the brain cells might be able to make use of the reintroduced enzyme to stop or reverse the damage caused by the accumulated materials,” said Davidson, who also is the Roy J. Carver Professor in Internal Medicine. “In the treated mice, the affected brain cells go back to looking normal, the brain inflammation goes away and the impaired behaviors that these mice have is corrected.”
To develop their gene therapy targeting system, Davidson and colleagues used a technique called phage panning to identify peptides that hone in on the blood vessels surrounding the brain. Surprisingly, they found that peptides that targeted the brain blood vessels in mice with lysosomal storage diseases were distinct from the peptides that targeted brain blood vessels in healthy mice. Moreover, the peptides that targeted blood vessels in different diseases were distinct from each other, suggesting that each disease causes specific alterations to the blood vessels.
The team modified a deactivated virus used for gene therapy so that the virus expressed copies of the unique brain-targeting peptide on its outer coat, and also carried the genetic blueprint for the missing enzyme.
The study showed that the modified virus targeted the blood vessels in the brain and caused the blood vessel cells to produce the enzyme. Most importantly, the researchers found that the enzyme was secreted into the brain tissue in sufficient quantities to correct the disease symptoms and problems.
The team was able to use this approach to treat two types of lysosomal storage disease in mice, suggesting that the approach could be used for other types of lysosomal storage disease and possibly other neurological disorders.
Thank you, Debra!
May 20, 2009 by Mommy
Filed under Bloggin' Mama
Just like my friend, Heather, and her husband, Jim, helping us raise money for Hannah’s fight (Makdan publishing), my friend, Debra, has offered to donate 30% of all sales of her absolutely adorable teddy bears and stuffed animals for Hannah’s cause!
For my Canadian friends, please take a moment and consider Bears N Buddies. She has been around for awhile, and she has such a huge heart. She donates often to causes she cares about, and I want to thank her and support her anyway I can!
See the cute teddy bears and stuffed animal kits! Thank you, Debra, for everything!
Ethan M, 23 months old with Gaucher’s type 2
May 10, 2009 by Mommy
Filed under Bloggin' Mama, Ethan GD2
This is a guest post from Tina M. from Kansas City, Missouri. She is the mom of Ethan, 23 months old, recently diagnosed with Gaucher’s Type 2.
When we found out that we were having a little boy, we were ecstatic. The pregnancy was going great. We had no complications until we hit the seven month mark. Then the complications started, and haven’t ended yet. Ethan James McKown was born at 33 weeks. He was 4lbs 2oz and 19inches long. He was a little guy, but we knew right away he was a fighter. He did well in the NICU for 3 weeks and we finally got to take him home on the forth of July 2007.
He always had large stomach but all the doctors in the NICU just simply said “he just has a large belly” and left it at that. We thought it was peculiar but we were so stressed with everything going on in the NICU that we didn’t think much of it at the time. Eventually he would grow out of it, right? We were wrong.
He went through a period where everything seemed to be getting back to normal. He started to get bronchiolitis/ bronchitis with severe double ear infections. We were fighting off every little cold and sniffle he would get. There was one night that we thought we were going to lose him. We knew he had a cold and we had taken him to his pediatrician and he gave us some cold medicine and said to keep and eye on him.
A couple of nights later we put him to bed and notice that he just wasn’t breathing right. We picked him up and tried to get him to respond to us or “liven” up a bit. He just looked at us exhausted, working very hard to breathe. When we couldn’t get him to keep his eyes open or breathe normally we decided we better take him to the ER. We went to the local hospital and it was a nightmare! They are not equipped to deal with a child that fragile and that little.
He was still very petite. Every nurse and every doctor in the ER were in that room. They did chest X-ray’s and everything else and finally made us leave the room because they had to put a breathing tube in. We were torn apart. Even the security guard who escorted us to the waiting room had tears in his eyes. We thought we were going to lose him. We called both of our parents at 2am and told them what was going on and sat and waited. The longest thirty minutes of our lives past by and we were finally allowed back to the room. He looked so helpless and completely drained of everything. The hospital had called for a transport to the area children’s hospital because they didn’t have the equipment to handle Ethan.
The children’s hospital was about a forty-five minute drive away. We got to the children’s hospital and were immediate reassured everything was going to be alright. We were in very good hands then. They admitted him to a room and he had a bad case of bronchitis and the flu on top of it. His poor little body couldn’t keep up but he sure was fighting hard! We were there for about a week and were released to go home.
Over the next 6 months or so we were in and out of the hospital at least once a month with respiratory issues, lack of weight gain, and various other issues.
Finally in April 2008 they admitted Ethan for failure to thrive and said that he wasn’t leaving until they found out what was wrong. They ran hundreds of tests in the week we were there. They first thought he had Cystic Fibrosis, but that test was negative. They drew more blood and finally told us we could go home because they would have to wait on results from some of the tests.
A week or two after we went home, we received a call stated plainly that we had an appointment in genetics the following week. That was it. No explanation, no reasoning, nothing.
May 5, 2008 two days after my husband’s 25th birthday our lives change forever. We met with Ethan’s genetics doctor and counselor and learned that he had Gaucher Disease. We had never heard of it and had no idea what we were up against. I have never felt so helpless or heartbroken in my life. They weren’t sure which type he had, but since he presented symptoms so early and already had neurological side effects, they were leaning towards type II but were hoping for Type III.
The next week he went into surgery to get a port placed so he could receive enzyme replacement therapy. We had quite the scare when he had trouble breathing after the sedation. About three weeks later, we received the results from his Type testing. While we were in the hospital with pneumonia, we found out that he had a homozygous L444P mutation. He had type III. We were so happy we cried that day. There was a chance for him. He would at least get treatment and hopefully live a healthy happy live. He was doing well with his treatments and everything was starting to get on track. He still wasn’t gaining weight, but his levels were good. Everything seemed to be looking up for us.
I went to visit my brother in Topeka, KS which is about an hour away. Ethan would have breath holding spells, but none were as bad as that night. He went into a fit while grandma was feeding him. I took him from her and he stopped breathing. I immediately started CPR and tried to get him back. My brother called an ambulance but I luckily got him breathing again before they arrived. That was the longest three and half minutes of my life!
After this episode, they scheduled a sleep study and realized that it was very dangerous for him to sleep. He would wake up about twenty times an hour because he would stop breathing. He was only getting two minutes of REM sleep a night. It was no wonder he wasn’t gaining weight. He was burning calories even when he was trying to sleep.
After seeing the results, the ENT clinic said that it was probably a good idea to have a tracheostomy tube put in. We were completely caught off guard with this. We didn’t know what to say but we had no choice. The risk of our son dying in his sleep was too high; we had to do the surgery. The scheduled it for the following day. They also did a surgery on his eyes to fix his strabismus.
When we saw him in the ICU after the surgery, I wanted to scoop him up in my arms and just go home. All we knew was our son was laying there with a tube in his throat to breathe through and blood filled tears. It was the most heart wrenching sight. He looked at us so confused. He couldn’t figure out why he couldn’t call out to us. He was trying to talk but no sound was coming out. His eyes would fill with tears which just made it worse. It is so hard to know that we won’t be able to hear his laugh again. We miss that more than anything.
He spent five days in the ICU and then another week on a floor before we were trained enough on how to take care of him.
A week before Christmas 2008, we went home and turned his nursery into a hospital room. We have oxygen sensors, liquid oxygen tanks, suction machine, CPR equipment, humidification machine. The list goes on. He started sleeping better and finally began to put on some weight, but not much.
In March of 2009 we had a gastrostomy tube placed and a nissen fundoplication because his acid reflux was so bad. He started to consistently gain weight and was doing better.
In April of 2009, they decided to send our blood off for more genetic testing because he was not responding to the treatments like a typical Type III patient would. We received the results a few weeks later. The results were not good. Ethan in fact has one copy of L444P gene and one copy of L444P, A456P, and V460V:1497G>C gene. His genetics doctors have never seen this variant of the disease before.
Ethan has Type II Gaucher Disease. Our world has changed forever. We just found out that our son probably will not live to see his third birthday.
We will be forced to stop his enzyme replacement therapy and he will slowly begin to fade away from us. We cannot understand why they will not allow us to continue the treatment when it seems to be doing him good. Why must they give up on our son?
