A new paper offers a possible road map for getting more drugs approved to treat rare diseases. One key recommendation: improving access to the FDA’s accelerated approval pathway, originally developed to quickly get treatments to patients with life-threatening diseases.

The paper, written by Brigitta Miyamoto and Emil Kakkis of the Kakkis EveryLife Foundation and published today in the Orphanet Journal of Rare Diseases, says the FDA should offer specific guidelines on how companies seeking to develop drugs for rare diseases can better utilize accelerated approval.

Kakkis helped develop and guide the approval process for three treatments for rare diseases at BioMarin Pharmaceutical, where he served as chief medical officer. He’s now CEO and president of Ultragenyx Pharmaceutical, which recently announced $45 million in financing to support the development of rare-disease therapies. (So he’d also benefit from anything that helped those drugs get to market more quickly.)

The FDA created the accelerated approval process in 1992 in the wake of advocacy by HIV/AIDS patients angry at the slow pace of drug development. It allows drug companies to ask FDA to approve a new therapy using so-called surrogate endpoints — blood tests, urine tests, or other biomarkers that likely predict a patient will benefit from a drug but aren’t on their own a measure of improved health. If the drug is approved, the company has to agree to keep testing to make sure that the results hold up.

(And sometimes they don’t. Just last week an FDA appeals panel recommended the revocation of accelerated approval for Avastin for use in breast-cancer patients after studies showed the drug provided minimal benefits.)

In less-common diseases, drug development is difficult all around. There is often very little understanding of the disease, its natural history and how to treat it, and scant data on managing or treating patients. That makes it very hard for companies to know what information the FDA will need to decide that a surrogate endpoint meets its standard of being “reasonably likely” to predict a benefit in a patient.

Anne Pariser, associate director for rare diseases in the Office of New Drugs at the FDA, tells the Health Blog that it’s crucial to be sure surrogate endpoints are valid indicators of the drug’s efficacy; some have failed to predict outcomes. So “you need evidence to support” any surrogate endpoints. She also notes that drug development fails for many reasons, so easier access to accelerated approval is no panacea.

Kakkis says his foundation plans to hold a workshop in the fall to jump-start a discussion on getting FDA to write guidelines on just how much evidence a company needs to meet the “reasonably likely” standard, and whether the criteria should be different for at least some rare diseases.

In the paper, Kakkis and his co-author identified 15 rare diseases where a treatment reversed the disease in animal models but still stalled in drug development. The reasons why varied, he said. Some were looked at by companies but deemed too expensive to successfully develop, others sat in academia without attracting investment. A few languished for years but are being considered again. All of them, he adds, could benefit by clearing the path to accelerated approval.

If anyone can do it, Dr. Emil Kakkis can.  One of the rare disease communities scientific champions (also one of GQ Magazines recognized Rock Stars of Science), Dr. Kakkis comes at his science with a passion and ferver that moves mountains.  How incredibly lucky is this community to have a scientist like Dr. Kakkis.  With very aggressive goals, Dr. Kakkis is working to bring 10 treatments to the community in 10 years!  Talk about accountability!!!    We are hopeful that this will become an important trend that is pursued by other biotechs, and that Dr. Kakkis like some of the other rare disease focused biotechs, will also show that it makes sense to invest in rare disease.  We are rooting for you and your team Dr. Kakkis!

Ultragenyx Announces Series A Financing
$45 million to support development of rare disease therapeutics

June 20, 2011 10:03 AM Eastern Daylight Time
NOVATO, Calif.–(EON: Enhanced Online News)–Ultragenyx Pharmaceutical Inc. today announced the closing of a $45 million Series A financing to support the development of rare disease therapeutics. The co-lead investors are TPG Biotech and Fidelity Biosciences, joined by European investor HealthCap, and Pappas Ventures. This funding will advance multiple rare disease product programs in the pipeline, as well as the development of new product candidates and partnerships. The lead product, UX-001, a first-in-class therapy for treatment of Hereditary Inclusion Body Myopathy (HIBM), is expected to enter the clinic in 2011.

“I am pleased and excited to have found a set of investors with the insight to support the development of a new rare disease company with multiple product candidates. They believe in the concept that a tightly focused company of committed rare disease development specialists will be able to create value as well as bring a series of novel, life-changing therapeutics to patients affected by rare and ultra-rare disorders,” said Emil D. Kakkis, M.D., Ph.D., Chief Executive Officer and President of Ultragenyx.

Dr. Kakkis formed and funded Ultragenyx in April 2010, based on his experiences in academia and over 11 years at BioMarin, where three rare disease products were approved during his tenure. The company has received additional funding from John Klock, M.D., and William Aliski, both experienced rare disease company executives. Joining the Ultragenyx Board of Directors are Eran Nadav, Ph.D. (TPG Biotech), Ben Auspitz (Fidelity Biosciences) and Mårten Steen, M.D., Ph.D. (HealthCap).

The company will be located in Novato, CA.

About Ultragenyx

Ultragenyx^TM develops therapeutics for rare diseases, sometimes referred to as Orphan products. Founded in 2010, the company is led by Emil Kakkis, M.D., Ph.D., former CMO of BioMarin Pharmaceutical. Efficient and effective development strategies are essential for success in the rare disease space, in which information may be incomplete or ambiguous, and few development precedents exist. The management team’s experience in selecting and developing products with clear mechanisms of action for untreated rare diseases will help Ultragenyx create life-changing therapeutics by leveraging existing yet undeveloped science for these little-known indications.

For more information on Ultragenyx, please visit the company’s website at www.ultragenyx.com.

It’s a Wrap – Rare Disease Day 2011.

DANA POINT, Calif. – The 4th Annual World Rare Disease Day took place February 28, 2011 with a fanfare of activities worldwide! Sponsoring organizations like NORD and Eurordis engaged in more activities and awareness efforts, garnering increased attention and engagement than previous years.

Once again, Global Genes Project™ helped support and create numerous opportunities to raise awareness for this important day through its grassroots campaigns and programs.

Wear That You Care™ Campaign took the world by storm!

Schools, Local Businesses, Disease Groups, Global Corporations were some of the hundreds of organizations participating in the Wear That You Care™ campaign supporting World Rare Disease Day 2011. “The goal of this campaign has always been to make it simple for people to participate and support rare disease families”, said Nicole Boice, co-founder Global Genes Project. “Rare Diseases are complex, the science behind the research is complex, the symptoms and medications are hardly pronounceable, making it difficult for the world to support this community in need”. It’s not easy to understand, and it is overwhelmingly scary for the general public. We are committed to changing that fact. The Wear That You Care campaign is something that is easy to participate in, helps provide an easy entry into supporting this community in need.

The Global Genes Project™ plans on continuing to make it easy to get engaged, show support, and build new champions for the millions of children and their families affected by rare disease. Global Genes Project™ will accomplish this through continued programs and educational efforts. “It is hard to generate support for something people don’t understand, we need to help them understand, in their terms, creating simple ways for people and organizations to support this community of millions”, Boice stated.

Global Genes Project – World Rare Disease Day report card

7,000 Bracelets for Hope™

• Hundreds of Bracelets donated and Hundreds of Bracelets distributed to rare disease families, in recognition of World Rare Disease Day.
• Bracelet Donations received from global designers from the Philippines, Austrailia, UK, Europe, United States.
• Bracelets distributed worldwide to countries like Mexico, Canada, Ireland, France, Australia, Hong Kong & Bangladesh.
• Efforts Continue: This very inspiring campaign will continue throughout 2011. The goal is to receive 7,000 bracelet donations and deliver them to 7,000 deserving families throughout the year. For more information on how you can help, join us at 7000 Bracelets

‘Blue Denim Awareness Ribbon’ Making and Distribution

• Over 20,000 blue denim awareness ribbons were made by volunteers and distributed around the globe in support of World Rare Disease Day.
• In addition to making this outreach possible through financial support, these organizations also recognized World Rare Disease Day by hosting events within their respective organizations, incorporating the blue denim theme; Pfizer, Shire, Illumina, Novartis, BioMarin.
• Kids Helping Kids Activities on campuses nationwide
• GlueDots™, making it possible for volunteers of all ages to help make ribbons
• Ribbon making activities will continue year round and are being offered to all rare disease advocates and groups for events, activities, etc.

NIH World Rare Disease Day Event

Global Genes Project recognition The Global Genes Project was very visible at the NIH for their first annual World Rare Disease Day Event. At the start of the day, Nicole Boice, co-founder Global Genes Project had the opportunity to present Dr. John Gallin (pictured top right), the head of the NIH Clinical Center with a denim ribbon and say a few important words about the Global Genes Project. Additionally, on the heels of a very compelling talk by Dr. Francis Collins (pictured bottom right), Director of the NIH, Nicole Boice and Audrey Gordon, executive director of Progeria Research Foundation, presented him with a 3ft denim ribbon and a ‘treatable’ tshirt. He reciprocated by having his first slide of his presentation being the Global Genes Project logo and Francis Collins in jeans! At the event, all attendees were given denim ribbons and many wore jeans in support of this campaign and the community as a whole!

Rare Disease Caucus – Extraordinary Measures Reception and Screening

John Crowley and the Rare Disease Legislative Advocates Group hosted a rare disease day (evening) event following the efforts at NIH. John Crowley, CEO Amicus and Pompe Disease parent advocate spoke to the group, which included Dick Gephardt (pictured right with Nicole Boice), House Majority Leader, who has been very supportive of the rare disease community and will continue to do so. Well attended, with support from PhRMA.

46NYC

Global Genes Project and 46NYC launched their ‘Treatable’ tshirt to benefit children and their families affected by rare disease. The campaign is on – all our children deserve treatments! – this is a powerful message and one that we can easily all participate in. We have lot’s of ideas about who needs to ‘be seen’ in a Treatable Tshirt! Send us pictures of you wearing yours and let’s post them on facebook!!! Stay tuned for more efforts related to the Treatable campaign.

Additional activities:

• 23andMe – providing new educational materials as resources for Global Genes Project partners and members, recognition of World Rare Disease Day through promotional efforts. www.23andme.com
• Healthline – Provided Awareness efforts and promotion the week leading up to World Rare Disease Day, providing information and support of the Global Genes Project efforts and insights into the rare disease community. www.healthline.com
• Keck Graduate Institute – Helped support World Rare Disease Day and distributed denim ribbons to all graduate students participating in an all day event. www.kgi.edu
• Lundbeck – Raise Your Hand event in Chicago at the NBC Studios. Kerry Hughes and Lori Butler represented both Battens Disease as well as The Global Genes Project where they distributed ribbons.

Thank you:

A Special Thanks to the current Global Genes Project Team:

• Chris Hempel – Addi and Cassie Fund
• Elizabeth Joshi – Joubert Syndrome Foundation
• Heather Earley – Russell-Silver Syndrome
• Sarah Goshman – Jacobs Cure
• Julia Jenkins – Kakkis Everylife Foundation, Rare Disease Legislative Advocates
• Lori Butler
• Kerry Hughes
• Eileen Braun – Angelman Syndrome Foundation
• Jennifer Thornton – AT Children’s Project
• Dean Suhr – MLD Foundation
• Amy Grover – RARE Project
• Wendy Liu
• The Team at Charleston Orwig
• SparkPR

Thank you to our supporters:

Don’t forget to join the discussion on Facebook, Twitter, and within the ‘Global Genes’ blog channel.

Ever want to be part of something bigger?  Ever want to really feel like people are helping champion your cause.  Well. . . they are.   The Global Genes Project was developed by the rare disease community, for the rare disease community.  The goals, to share with the world and educate about the needs of this community, raise awareness globally and ultimately help raise much needed funds for ‘in their lifetime’ research and therapy development.

Global Genes Project and World Rare Disease Day

There has been amazing momentum since the launch of this campaign 1 year ago.   As a result, we have hundreds of rare disease advocacy groups involved and thousands of individuals, engaged, getting involved, volunteering, and helping spread the word.   This campaign has started building real unity within the rare disease community and is working to help engage new champions to help all our efforts!

Some of the great programs underway:

7K Bracelets of Hope - volunteers, designers, children’s groups have all started sending beautiful hand made bracelets that we will be distributing to families around the globe.   We won’t stop until we have received 7,000 bracelets and have distributed them to 7,000 families.  This 7,000 number is representative of the 7,000 different rare diseases and disorders that have currently been identified.   It has been really amazing to see bracelets come to us from around the world, with personal notes of support for those recipients.  The main message is that ‘they are not alone’, and that there are many people out there that want to help and show there support.   Inspiring!!!  Please join us at www.globalgenesproject.org and join this campaign today – and pass it on!

Global Genes '7,000 Bracelets for Hope' supports World Rare Disease Day

Blue Denim Ribbon Making and Distribution - We have had volunteers (mainly made up of children) participating in ribbon making efforts since November.  Communities are coming together to help.  Corporations are jumping in to support this effort as well.  We will be distributing these ribbons leading up to World Rare Disease Day, Feb 28.  And ribbons are officially being sent around the world in recognition for this important day.   Corporate Support has come from; Pfizer, BIO, Shire, Genzyme, BioMarin, Healthline, Illumina, with more joining and supporting every week.  We thank these organizations, it is because of their involvement that we can provide many of these resources and programs to the community.

How can you get involved – Host a denim event in your community, Host a bracelet making party, Wear Jeans, Wear Blue Denim Ribbons, join us at www.globalgenesproject.org for more information and ideas.  And also join us online at Facebook, there you will also hear from many of the community member sharing ideas!!

Make a Difference Today!

Nicole Boice, Founder RARE

Matthew Herper

The Medicine Show; FORBES

November 2010

Right now drugs for rare disorders are the sweet spot of the biotechnology industry. Treatments for illnesses that affect only hundreds of patients can cost $200,000 or more and have built Genzyme into one of biotech’s biggest companies and Alexion and Biomarin into two of its hottest names for investors. Shire has moved into the field in a big way, and Novartis and Pfizer look likely to follow.

But most of these disorder go untreated.

In a speech at the annual meeting of the American Society of Human Genetics on November 6, Francis Collins, the director of the National Institutes of Health and the man who headed the Human Genome Project, implored his colleagues in genetics to work to develop new treatments for rare diseases. His point was that the NIH and the Food and Drug Administration are increasingly able to handle preclinical and early clinical drug development, and that with these first steps taken medicines are more likely to be brought to market by large pharmaceutical companies.

Kicking drugs far enough along that they become appealing to drug giants  is a great strategy. It has worked phenomenally for organizations like the Cystic Fibrosis Foundation and the Multiple Myeloma Research Foundation. It’s why Gilead sells a cystric fibrosis treatment and Vertex is working on one. This is a smart approach for academic researchers to take if they want to develop drugs. Contrary to popular belief, academia and government don’t invent many drugs. A recent scientific paper estimated taht  76% of drugs are invented by large drug firms. The other 24% start in academia and end up at drug companies.

In arguing for the great need for these treatments, Collins said 7,000 diseases affect people, but that only a small fraction support the commercial development of drugs. More than 6,000 of these disorders are rare diseases, most of them caused by a single gene, and fewer than 200 have a drug treatment available. Cumulatively, these orphan disease afflcit 25 million to 30 million people. That’s a pressing need — and a huge market.

If effective treatments for those 30 million people cost $200,000 a year, the bill for treating all of them would be $6 trillion. But not all orphan diseases claimthe $200,000-plus price tag; some drugs for more common orphan disorders like pulmonary arterial hypertension cost $50,000 a year. But if we assume a comparatively cheap average price of $33,000 annually for a new orphan disease drug, treating every patient with an orphan disease for a year would cost $1 trillion. That’s bigger than the entire global pharmaceutical market, which IMS Health projects will hit $880 billion next year.

Of course, many patients with rare diseases actually receive their medicines for free if insurers or governments cannot pay for them. And, more importantly, we’re nowhere near having 6,000 treatments for 6,000 orphan diseases. If we doubled or tripled the number of rare disease drugs over the next decade it would represent a stunning spate of innovation and still leave us with only hundreds of medications.

But this is a real reminder of how big a market has to be to get companies to develop a new treatment, and that’s a fundamental fact – and challenge – when it comes to curing any disease. People tend to think of the profits that pharmaceutical companies make as payment for the research they do. But it’s more like the jackpot in a lottery — a very big prize most drug developers will never get. (Collins also noted that only 5% of drugs that start development make it to market.) If the pot isn’t sufficiently big, the money gets invested somewhere else.

The former chief medical officer at BioMarin Pharmaceutical Inc. — the Novato-based poster child for developing treatments for so-called orphan drugs — is lining up cash and personnel for a new venture again aimed at rare diseases.

“When you see patients treated for the first time, you don’t forget that,” Kakkis said. “You want to do it over and over again.”

Whether Kakkis’ new company, Ultragenyx Pharmaceutical, can add to his string of successes depends largely on lining up financing. He hopes to have Series A funding of “substantially more” than $10 million secured by April and 20 to 25 employees by June.

That may seem like a tough chore in a financing environment that has slowed venture investing in startup biotech companies. Orphan drug companies, however, are hot properties that some experts say can net relatively quick returns on investment for investors.

“VCs are always looking for the next big thing, and orphan drugs is really one of the next big things,” said Eric Nelson, business development lead for the National Institutes of Health’s Therapeutics for Rare and Neglected Diseases program. “Large pharma and specialty pharma are looking for big opportunities.”

Last year alone, 49 rare diseases were discovered, Nelson said. “There’s just a lot of opportunity for new drugs,” he said.

BioMarin, for one, has shown money can be made by focusing on enzyme replacement treatments for diseases with 200,000 or fewer patients that few people know about. Aldurazyme and Naglazyme, BioMarin’s therapies for the lysosomal storage disease MPS, are among the priciest drugs in the world at $200,000 and $375,000 annually, according to Forbes. BioMarin lost $488,000 on revenue of more than $324.6 million last year.

As an assistant professor in the genetics unit of the pediatrics department at Harbor-UCLA Medical Center, Kakkis and Elizabeth Neufeld discovered what would become Aldurazyme. After joining BioMarin in September 2008 — then a company less than 2 years old — he also oversaw development of Naglazyme and Kuvan, a treatment for the metabolic disease phenylketonuria.

Orphan drug development carries tax and intellectual property benefits, including tax credits and seven years of market exclusivity. But as orphan drug development companies have grown, small-market products “don’t move the needle for them anymore,” said Kakkis, who retired from BioMarin in February 2009 and has since run the Kakkis EveryLife Foundation in Novato, an organization aimed at improving the regulatory system for rare diseases.

Ultragenyx already is working on its first small molecule drug — aimed at a biochemical disorder that affects skeletal muscle — with a small Japanese pharmaceutical company handling manufacturing and preclinical work. Ultragenyx also has a collaboration with an academic researcher on a second drug and is working on three other experimental treatments for diseases that Kakkis wouldn’t specify. Among Kakkis’ heady goals for Ultragenyx is to take the lead drug into the clinic by July 2011 and complete the proof-of-concept study within two years.

“We’re going to show how fast things can get done with planning and execution,” Kakkis said. Kakkis has seen the process work quickly before. At BioMarin, for example, it took Kuvan just three years to go from its investigational new drug application to approval by the Food and Drug Administration, and it took Naglazyme, despite only 300 patients identified at launch, five years.

The average pharmaceutical drug takes 10 years to get from IND to approval. To do that, Ultragenyx will create a boilerplate registry system to find patients over a variety of orphan diseases. That is important because orphan diseases can be so rare that there are no advocacy organizations or other way of finding out exactly how many people have the disease, much less who is eligible for the necessary clinical trials.

Such a system can knock months, if not years, off clinical development.

“Rapid development requires insight and expertise. But you have to stay focused,” Kakkis said. “In rare diseases, you can go on forever,
because there’s so little known.”

DANA POINT, CA – February 1, 2010 – Hope – It’s In Our Genes.™ The Children’s Rare Disease Network today announced the Global Genes Project, an initiative designed to raise awareness about the prevalence of rare diseases that afflict millions of children worldwide. Rare disease advocates organizing the campaign selected a blue jeans denim ribbon as the international symbol of hope for children suffering from life threatening and chronically debilitating rare diseases.

More than 90 corporations, non-profit foundations, research institutions and children’s hospitals have signed on to support the Global Genes Project including: 23andme, Amicus Therapeutics, Better Health, BioMarin, CheckOrphan, CollabRx, Counsyl, Coriell Institute, DonateGames.org, FasterCures, FreeForm, Genetic Alliance, Geni.com, Genzyme, Hide and Seek Foundation, Jackson Laboratory, Kakkis EveryLife Foundation, Knome, Lili Claire Foundation, Life Technologies, Mayo Clinic and Shire.

Numerous rare disease foundations from countries including Australia, Argentina, Belgium, Canada, China, New Zealand, Philippines, the United Kingdom and United States are helping support the global movement by organizing activities throughout February and leading up to World Rare Disease Day 2010.

“The Global Genes Project is providing a new platform to help unite people under a common goal and to make a difference for all children suffering from rare disease,” said Nicole Boice, Founder, Global Genes Project. “We want to create a world where children suffering from chronic disease have equal access to life saving drug treatments.”

Growing Public Health Concern; Inequity Exists

Rare disease is an important and growing global public health concern that can no longer be ignored. While each disease may be rare when considered by itself, rare disease collectively impacts the lives of millions. According to estimates from the National Institutes of Health (NIH), approximately 6,800 rare diseases exist, many of which are genetic in origin, translating to an affected population of 25-30 million Americans or approximately 1 in 10 people. In Europe, the number affected is almost identical. Approximately 75% of those affected by rare diseases are children, making the rare disease category one of the most deadly and debilitating for children worldwide.

Despite the success of the Orphan Drug Act of 1983, pharmacologic treatments exist for only a small fraction of rare diseases, or approximately 200 of the 6,800 rare diseases. After 25 years of orphan drug regulations and legislation, the development path to approve new drugs has not stimulated orphan drug development for small populations of patients facing rare disease.
Current studies also suggest that it takes more than a dozen years and hundreds of millions of dollars to take a potential drug from discovery to the marketplace. As a result, severe inequity exists in access to care and treatment for millions of rare disease patients.

Denim Blue Jeans Ribbon Campaign

Leading up to the annual World Rare Disease Day on February 28, 2010, the Global Genes Project will help facilitate a series of denim focused awareness events, charitable activities and engage corporate sponsors, government officials, celebrities and the media to help spread its lifesaving message of hope.

“Blue is the color of strength and our blue jeans denim ribbon is an ideal symbol that expresses solidarity,” added Boice. “Genes and jeans are a natural fit – both are universal, come in pairs and are unique to the individual. It’s a simple concept that anyone can embrace and a powerful way to raise awareness for rare disease.”

The Global Genes Project is asking rare disease advocates and supporters across the world to wear denim jeans and blue jeans denim ribbons the week of February 22 and leading up to World Rare Disease Day 2010. The organization is also asking supporters to display the blue jeans denim ribbon symbol on their websites and to actively invite co-workers, friends and family and their community to join in spreading this global message.

Blue jeans denim ribbons can be obtained by visiting www.globalgenesproject.org. Denim jeans and ribbon wearing supporters can submit digital photos on Facebook. To join the growing list of supporters, visit http://www.globalgenesproject.org/sponsors.php.

About The Global Genes Project

The Global Genes Project is a campaign of the Children’s Rare Disease Network and a grassroots effort with the goal to increase awareness about the prevalence of rare diseases worldwide. The Children’s Rare Disease Network is a registered 501c3 non profit organization. For more information, visit www.crdnetwork.org or www.globalgenesproject.org.