Pfizer’s Viagra Faces FDA Review for Use in Children With Lung Condition

By Shannon Pettypiece and Molly Peterson – Jul 27, 2010

A form of Pfizer Inc.’s erection drug Viagra, sold as the blood-pressure treatment called Revatio in adults, may be used for children with a rare lung disorder if U.S. regulators can agree on how to test it.

The condition, called pulmonary arterial hypertension, affects only 600 children a year, New York-based Pfizer said. It causes high blood pressure in arteries in the lungs, making the right side of the heart work harder than normal and causing chest pain, dizziness and fatigue. Outside advisers to the Food and Drug Administration are set to meet July 29 to evaluate whether Pfizer’s study of Revatio is sufficient to determine its effectiveness in children, the agency said today.

If the New York-based company meets FDA requirements, the drug would get an extra six months on the market without generic competition. Patents on the drug, with 2009 sales of $1.89 billion as Viagra and $450 million as Revatio, are expected to expire in 2012. Some doctors are already using the treatment in kids with the lung condition.

“It’s a good option in pediatric patients because it is well-tolerated, in that it doesn’t have as many side effects as some of the other options,” said Chad Knoderer, a pediatric clinical pharmacist at Riley Hospital for Children in Indianapolis, who has used Viagra in kids with the disorder.

FDA Request

The FDA in 2001 asked Pfizer, the world’s biggest drugmaker, to study the medicine in children with the lung disorder. Sildenafil, the chemical name for both Viagra and Revatio, blocks an enzyme found in the lungs and penis that regulates blood flow. Pfizer is considering whether to seek approval for Revatio, a lower-dose form of sildenafil, in children, said Colin Ewen, an executive director at the company, in a July 23 telephone interview.

Pfizer shares rose 16 cents, or 1.1 percent, to $15.18 at 10:09 a.m. in New York Stock Exchange composite trading.

The FDA is asking its panel of advisers to decide what is the best measurement to use in determining if the drug is effective in children with pulmonary hypertension.

In adults, researchers typically use an exercise test to determine if the drug is having a benefit. Because that test was difficult to perform in young children, Pfizer has asked the FDA to consider an alternative test that measures blood flow by inserting a catheter through the arteries.

In Pfizer’s study of 234 children, the drug failed to show a benefit when the children’s exercise ability was measured. However, it did show a significant benefit when researchers used an alternative measure of blood flow.

NIH Takes On New Role in Fight Against Rare Diseases

July 24, 2010

By AMY DOCKSER MARCUS

A government program focusing on rare diseases has launched five pilot projects that are taking the National Institutes of Health in a new direction: developing drugs.

The NIH Therapeutics for Rare and Neglected Diseases (TRND) program was established last year with $24 million of funding. TRND will work together with scientists, advocates and others to do the required research and testing on drugs before a compound can be tried in humans in a clinical trial.

Promising new drugs discovered through basic research often flounder during this stage of the process, which is expensive, time-consuming and prone to failure.

The pilot projects, three of which were selected this spring, target drug development for sickle-cell disease; chronic lymphocytic leukemia; the fatal neurodegenerative disease Niemann-Pick Type C; the genetic muscle disorder hereditary inclusion body myopathy; and the parasitic diseases schistosomiasis and hookworm.

The projects, which are in various stages of development, were selected because they illustrate a range of problems and issues in the effort to drive drug development.

The problems include the high cost of studies in animals to determine if a drug is too toxic to give to humans, the challenges of meeting regulatory requirements before the Food and Drug Administration allows clinical trials to begin, and the sheer amount of coordination that goes into getting a new drug to market.

“Most of the problems we are addressing are not scientific problems,” said Christopher P. Austin, director of the NIH program. “They are operational issues.”

For most new drugs, these issues are handled by a pharmaceutical company. Rare diseases, which the NIH defines as diseases that affect fewer than 200,000 people in the U.S., represent a small market.

As a result of the small markets, many pharmaceutical companies are reluctant to take on the risks and expense of trying to develop new drugs for these conditions.

TRND is assigning project managers with experience in drug development to the pilot projects to help identify the necessary steps to get to clinical trials.

The sickle-cell disease project, for instance, involves AesRx LLC, a Newton, Mass., biotech company, and needs to complete toxicity studies and regulatory work to launch a trial.

“The alternative would be to raise outside capital from venture capitalists,” said Steve Seiler, chief executive of AesRx. Mr. Seiler said at this stage of the project it would have been difficult to get the financing. “Once we have human clinical data, it is much different,” he said.

With the muscle disorder hereditary inclusion body myopathy, William A. Gahl, clinical director of the National Human Genome Research Institute, said he had been unable to launch a clinical trial to test a promising compound for three years, before the project was taken up by the NIH program.

He said that before he could start a clinical trial with the compound, the FDA wanted toxicology studies conducted in animals, at an estimated cost of $500,000 to $1.5 million—money the small biotech company and patient advocacy group he is working with didn’t have available. “We were about to give up,” Dr. Gahl said.

TRND is getting toxicology studies done and has hired a regulatory consultant to help address any regulatory issues with the FDA to get permission to start a trial.

“TRND has smoothed the way enormously,” said Dr. Gahl, who said he hopes to launch the trial this year.

In the case of Niemann-Pick Type C, TRND’s Dr. Austin had previously worked with a group of scientists and parent funders called SOAR-NPC to screen already approved FDA compounds to see if they might be effective against the disease. A promising compound was identified, but extensive work will be required to determine whether the drug is safe and effective enough to be tried in patients, Dr. Austin said.

This kind of tinkering with a promising drug—testing it in animals and then going back to the lab for further tweaks—is both time-consuming and expensive, and can be out of the reach of a parent-funded organization like SOAR.

Last week, at the annual conference of the advocacy group Genetic Alliance, Dr. Austin, a parent funder in SOAR, and Steven U. Walkley, a professor at Albert Einstein College of Medicine who is a member of SOAR, gave a joint talk that addressed some of the pressures the NIH program faces.

“There is a lot of promise built in to TRND, but there is no guarantee that they will be able to make the science deliver a therapy for a disease,” Dr. Walkley said.

Dr. Austin said he recognized that “we have to succeed with these pilot projects, and if we don’t, the program won’t continue.”

Half of the program’s budget this year is going to fund the five pilot projects, he said. The other half of the budget is going to setting up TRND. Dr. Austin added that the program plans to solicit additional projects in September.

Link to article

NORD Testifies Before Senate HELP Committee

July 21, 2010

WASHINGTON DC – An advocate for people with rare diseases today told a U.S. Senate committee that the burden of funding and driving research on rare diseases too often falls upon patients and their families.

“As a society, it is wrong for us to expect people with devastating diseases to fund the search for their treatments,” said Diane Dorman, vice president for public policy of the National Organization for Rare Disorders (NORD). “There are nearly 7,000 rare diseases, and only about 200 of them have treatments. Many are not being studied by any researcher in government, academia or industry.

“Through golf tournaments, raffles…even bake sales and car washes, it’s too often the patient community that funds and drives rare-disease research. We need a more significant commitment at the federal level.”

Dorman said the word “rare” is misleading, since about one in 10 Americans have diseases classified as rare. While each disease is unique, there are many problems and challenges that all people with rare diseases share, she added.

Dorman told the committee that federal funding and guidelines are needed for natural history studies, patient registries and other basic tools to make clinical research possible. And, she said the Food and Drug Administration (FDA) should institute a statement of policy on rare diseases and orphan products to reduce regulatory uncertainty and encourage researchers to develop treatments for diseases that have none.

She also urged the nation’s medical schools to enhance training on rare diseases. “NORD believes our nation is blessed with a caring and dedicated medical establishment,” she said. “But we urge a greater emphasis on rare diseases in medical education centers to prepare young clinicians to treat these diseases and encourage young investigators to study them.”

Dorman made her comments in invited testimony before a Senate Committee on Health, Education, Labor, and Pensions hearing on the topic, “Treating Rare and Neglected Pediatric Diseases: Promoting the Development of New Treatments and Cures.” The hearing was co-hosted by Committee Chair Senator Tom Harkin (D-IA) and Ranking Member Senator Michael B. Enzi (R-WY).

To address the lack of treatments, Dorman told the committee, NORD has launched several recent initiatives that offer hope for the future, working closely with FDA and the National Institutes of Health. These include:

• · a new training course and a handbook to prepare researchers for the special challenges of studying rare diseases
• · a task force to help NIH and FDA identify ways to work together more effectively and
• · a series of focus groups through which stakeholders—academic researchers, patient organizations, industry, and investors— share their views with NIH and FDA officials.

NORD is a non-profit organization representing all Americans with rare diseases. It was founded in 1983 by leaders of patient organizations and provides programs of education, advocacy, patient services and research.

A Great Win for Rare Diseases in U.S. Senate Appropriation Bill

New FDA funding and requirements for guidances will help give rare diseases access to the accelerated approval process.

July 15, 2010 (Novato, California) — Just 16 months after the Kakkis EveryLife Foundation kicked off the CureTheProcess Campaign, the Foundation, in association with the National Organization of Rare Diseases (NORD) and numerous other patient and physician organizations, have increased the support and commitment to improving rare disease regulatory policies.

A US Senate Appropriation bill has been submitted including language supporting two of the Campaign’s goals. Specifically, the Bill supports the creation of new guidances which could improve the scientifically sound use of surrogate endpoints and new clinical study designs and analysis. The Senate Bill also includes an appropriation for the Food and Drug Administration to hire new staff to fulfill these requirements.

“We are especially grateful to Senator Sam Brownback (R-KS) for his leadership on this issue and to Senator Herb Kohl (D-WI) for his support,” said Emil Kakkis, M.D. Ph.D., President of the Kakkis EveryLife Foundation. “We are very pleased to see so much progress made, in such a relatively short time.”

The Senate Appropriations Committee will now review the FY 2011 Agriculture, FDA, and Rural Development Appropriations Bill. The bill includes the first increase for the Orphan Product Development Grant program since FY 2005. The program is increased by $2,000,000 for a total grant level of $16,035,000. The Bill also includes specific funding for the Office of the Associate Director for Rare Diseases in the Center for Drug Evaluation and Research (CDER). Funding for this office is increased by $1,000,000 to hire additional staff with specific expertise in facilitating the development and review of products to treat rare diseases.

The manager’s package that should be adopted at Committee includes language, cleared by the FDA that builds on the Brownback/Brown Amendment language that was included in the FY 2010 Appropriations Bill (Section 740). The language requires the FDA Commissioner to “…develop updated guidance documents and review standards for the development of safe and effective products to treat rare diseases and neglected tropical diseases…”

Specifically, the Bill spells out requirements to:

• Maximize the use of accelerated approval where feasible and appropriate, including guidances on the use of surrogate endpoints that are reasonably likely to predict clinical benefit of drugs and biological products under the regulations under Subpart H
• Work with drug company sponsors to facilitate expanded access to investigational therapies
  Develop guidance on clinical development programs for rare diseases
• Increase coordination among individual drug, biological product, and device review divisions across FDA centers to support the development of safe and effective medical products for rare and neglected diseases

The FDA is required to implement these as a part of the FY 2010 Brownback/Brown Amendment reforms and report back to the Appropriation Committee on implementation of these items.

“The Senate Bill is a good step forward in improving the regulatory process for rare diseases. By creating a more predictable pathway for orphan treatments, we will shorten development timelines and reduce the financial risk associated with the development of rare disease therapeutics. The result will be a surge in development activity for even the most rare disorders, giving more patients with rare biochemical and genetic disorders earlier access to effective treatments.” said Dr. Kakkis.

The Foundation initiated the CureTheProcess Campaign to give even the rarest diseases access to the accelerated approval process and put treatments on the fast track. There are more than 7,000 rare disorders that together affect over 25 million Americans and their families; however less than 5% have treatments as few drug companies conduct research on rare diseases since it is currently difficult to recoup the costs of developing treatments for such small populations. More than 130 patient and physician organizations have endorsed the Campaign goals to:

1. Establish a new Office of Drug Evaluation for Genetic and Biochemical Diseases at the FDA, consolidating and expanding expertise to ensure safe, effective and timely patient access to needed treatment.
2. Create a new standard to qualify biomarker or surrogate measures of the effect for treatments of rare disorders, and allow these treatments full access to the accelerated approval pathway for life threatening diseases.
3. Devise new clinical study designs for rare diseases that account for disease complexity and patient variability to properly capture treatment effects on all aspects of the disease.

To learn more about the Kakkis EveryLife Foundation, please go to www.Kakkis.org.

Regulatory Flexibility

Patient advocates call on FDA to develop policy that would speed development of new therapies for rare disease.

Rare disease patient advocates called on the U.S. Food and Drug Administration to remove regulatory uncertainty and allow for greater flexibility in how the agency reviews drugs for diseases afflicting small populations of patients. The call came during a two-day public hearing held by the agency as it seeks ways to spur drug development around diseases where markets may be too small to entice drugmakers to make the large investment needed to bring drugs to market for these conditions.

“No one is arguing against rigorous standards, it’s just the standards for rare diseases need to take into account the size of the patient population and the devastating nature of these diseases,” says Jonathan Jacoby, CEO of the RARE Project, a group that advocates for accelerated rare disease research.

There are about 7,000 diseases that are considered rare and treatments for only about 200 of them. A disease is considered to be rare if it afflicts 200,000 people or less. Though individually each of these diseases is rare, about 10 percent of the population suffers from a rare disease.

The FDA’s 2010 appropriations bill required the agency to convene an expert committee to review the ways the agency deals with therapies to treat people with rare diseases. As part of that effort, the expert committee held the hearings as a way to reach out to patients, their families, patient advocates, drugmakers and researchers for their input.

Frank Sasinowski, chairman of the National Organization for Rare Diseases, said in a statement at the hearing that the FDA in the 1980s put into place regulations in response to the AIDS crisis that provided for flexibility in applying standards to drugs in development to treat life-threatening and debilitating illnesses in order to speed the development, evaluation, and availability of new drugs.

“When these trials are conducted, sometimes with designs with which all parties may not be in full concurrence, including the FDA, great deference should be afforded the design of these trials and flexibility applied in the interpretation of their results,” says Sasinowski. “If such a principle were to be addressed and accepted by the FDA, much good would come of it.”

Children’s Rare Disease Network Partners With Medpedia.com To Create Rarespace

Online Knowledge Share Platform to Provide Valuable Information to Rare Disease Community

Dana Point, Calif. (June 29, 2010) – Every parent needs a supportive, collaborative network full of information where medical professionals, researchers, patients, parents, advocates and the general public share knowledge about the rare childhood diseases that affect 22.5 million American families. RareSpace is an online knowledge sharing platform designed in partnership with R.A.R.E. Project, the Children’s Rare Disease Network and Medpedia.com to help grow resources for children with special needs. This resource is available online now at RareSpace.

“RareSpace is a unique and valuable tool for families caring for children with rare diseases,” says Jonathan Jacoby, CEO of the R.A.R.E Project. “With the help of Medpedia.com, RareSpace will become a safe place to share important information aggregated from the rare disease community at large, which is vital to finding hope for children.”

It’s the collaborative structure of RareSpace that makes it truly unique. The site will educate and connect users about critical resources, innovations in research, standards of care as well as best practices in treating rare diseases and disorders. Creating a community filled with medical professionals, policy advocates, researchers and parents catalyzes a free exchange of information, increasing the general knowledge quotient of every stakeholder. The goal is to supply real resources and connections for those who are in the care of children living with rare diseases and disorders, and help each family not feel isolated in their struggles to care, treat and advocate for these sick children.

“It’s so critical for families and caregivers to have a knowledge bank like RareSpace to draw from,” says Devon Watts, community manager at Medpedia.com. “We are excited that Medpedia.com is a part of connecting a community and granting an open space for dialogue and education. It’s the widespread sharing of information that will benefit patients most.”

Different from other community sites, one key advantage of RareSpace is that people can share documents and resources very easily. Discussions of genetics and genetic diseases in general happen on RareSpace, with the understanding that research on all these diseases could lead to cures for other genetic disorders as well. Articles on translational research and discussions of possible cures for diseases can be found on RareSpace. A major benefit is that medical professionals will answer questions posed by site users about treatment, best practices and how to best help these children and their families. Users will create profiles and have the opportunity to upload documents and links and connect with other users all within the RareSpace portal. In addition to connecting within RareSpace, users will have the ability to create disease specific groups that can all be linked with RareSpace. This robust platform provides numerous ways to share critical information and knowledge across the rare disease community, which can be done in a safe environment that includes representation from all of the key stakeholders involved in rare disease.

R.A.R.E. Project’s, Jonathan Jacoby to present at FDA Hearing on Rare Disease

On Tuesday, June 29, 2010, and Wednesday, June 30, 2010, FDA’s Office of Orphan Products Development will host a two-day public hearing and Webcast on the Development of Articles for Rare Diseases.

This public hearing is intended to gain from health care providers, academia, industry, patients, and other interested persons their perspectives on various aspects of the development of medical products for the diagnosis, treatment, or management of rare diseases. The input from this public hearing will help inform the work of FDA’s committee for rare diseases

Jonathan Jacoby, CEO R.A.R.E Project will present case studies on therapeutic candidate generation, focusing on;

• Challenges of patient-driven R&D
• Challenges and successes with biomarker identification
• Experience with Orphan Drug Designations
• Individual investigator INDs and IND exemptions
• NIH clinical trials
• Barriers to recruitment and participation in CTs

Following the presentation, Jacoby will provide recommendations that include the importance of very small CTs as a pathway to regulatory approval. Jacoby will present this testimony from 11:40 – 12:00, June 29, 2010.

The meeting will be webcasted and any interested persons are encouraged to join:

• Dates: June 29-30, 2010
• Time: 9:00 AM to 5:00 PM ET
• Webcast addresses (will be active at the time of webcast):
  June 29 – collaboration.fda.gov
  June 30 – collaboration.fda.gov

FDA Database Aims to Spark Orphan-Disease Drug Development

By Amy Dockser Marcus

For months now, the Food and Drug Administration has been trying novel ways of encouraging drug makers to develop drugs for rare diseases.
Today the agency’s Office of Orphan Products Development is launching a new gambit—a database of FDA-approved compounds and products that show promise in rare diseases too.

The concept is called “repurposing” — finding new ways to use products that have already been okayed by the FDA for some other use.

The already-approved products in the Rare Disease Repurposing Database are unique in that they’ve also previously received orphan-drug designation, meaning they’ve shown potential to treat one or more of the diseases affecting 200,000 or fewer Americans. (While orphan-drug status doesn’t guarantee FDA approval as a treatment for the rare disease, it’s a prerequisite for getting incentives such as tax breaks and marketing exclusivity if the agency does okay the drug for that purpose.)

Timothy Coté, director of the orphan products development office, says that testing an already-approved drug as a treatment for a rare disease has significant advantages — for one, it’s already been found safe by the FDA. And running trials on an existing drug is much cheaper than trying to develop a totally new compound.

Despite the incentives in the Orphan Drug Act, there are only about 350 such drugs that have been approved — and there are some 7,000 rare diseases.

Information in the database is already publicly available through the FDA but until now has been scattered. Coté says officials went through more than 2,000 orphan drug designations to compile the new 235-drug database, which he says is likely to be used not only by drug companies but also by venture capitalists looking for promising investments and patient advocacy groups eager to drive drug development for their rare condition.

Coté says he hopes the new database will spark drug development efforts. But he plans to do some repurposing of his own. He says the next step after the database is released is for his office to carefully study the list, identify some particularly promising products, and urge the companies to move forward.

Link to article

Father’s Day Turns 100!

We know some amazing dads who work so hard caring for kids with rare diseases. This year we want to celebrate them!

Father’s Day turns 100 on June 20, 2010.

EXCLUSIVE: Pfizer Plans to Move Fast on Rare Disease Pacts

Pfizer went public with its new rare disease unit earlier this week, but one of its top execs has been working away for the past few months setting up a division that is preparing to team up with a range of biotechs on new therapeutics.

“This morning at 7 a.m. I was at breakfast, talking to a company,” Jose Carlos Gutierrez-Ramos, Pfizer’s Cambridge-based senior vice president for biotherapeutics research and development, tells FierceBiotech. “We are actively talking to people and have been for the last two months.”

Pfizer isn’t just interested in partnering with biotechs working on new drugs for rare diseases. The company also wants to forge close ties with leading academics as well as key patient associations, several of which have taken an ambitious lead in funding studies of experimental therapies. In some cases, three-way pacts partnering Pfizer with a patient association and a drug developer could make sense.

“We’ll do internally what we do well,” he adds, “and what we don’t do well we’ll do externally with others.” Dr. Edward Masciolo, who had founded Dapis Capital, will head the unit and report to Gutierrez-Ramos.

The goal is to create a small, “highly virtualized, highly focused” group that will start inking pacts in the next two to three months as it builds a significant pipeline of new drugs over the next two to three years, says the Pfizer exec.

“We are very interested in certain areas,” he adds, highlighting hemophilia, muscular dystrophy and protein misfolding. “There are certain areas where we have biases,” with the seriousness of the disease and the impact Pfizer can make on it the two leading indicators of where it will focus its resources.

But Pfizer isn’t starting completely from scratch, either. The pharma giant has spent years developing new hemophilia therapies and recently licensed Protalix’s Gaucher’s drug, which will put it in direct competition with Genzyme, a large cap company that has made a big mark selling some very expensive medications for rare diseases. Genzyme’s successes with drugs like Cerezyme helped inspired GlaxoSmithKline to start their own rare disease unit back in February.

“We have significant expertise in rare diseases,” Gutierrez-Ramos says. “We’ve worked in hemophilia for 10 years and as a consequence of that we have developed a protein therapeutic and protein replacement capability and know-how that is unlike few other companies.” – John Carroll

Link to article

Next Page »