Bill provides incentives for research, development into pediatric medication

Pediatricians are familiar with the urgent need for research into medications for children, but the demand for these medications is low and a myriad of hurdles are involved in bringing them to market.

A partial solution to both of these problems may be the Creating Hope Act, a bill under review in the US Senate Committee on Health, Education, Labor and Pensions. This legislation, introduced by US Sen. Robert Casey Jr., D-Pa., on March 17, provides a voucher-based system that entitles pharmaceutical companies priority review on any other products, for any indication, they may be developing, in exchange for an FDA-approved drug for a pediatric rare disease. These vouchers would also be transferrable.

“Pharmaceutical companies can use this incentive to get a bigger bang for their dollar,” said Edward Connor, MD, who is director of the Office of Innovation Development and Investigational Therapeutics at Children’s National Medical Center in Washington, D.C. “If you are a larger pharmaceutical company, this could mean more rapid approval on a medication that may go to a larger market.”

Connor and colleague Pablo Cure, MD, MPH, also of Children’s National, recently wrote a commentary on the Creating Hope Act because, Cure said, this piece of legislation, along with others like it, “incrementally get us to a better place in which there are incentives for developing medications in children.”

Although children make up nearly 40% of the world’s population, little research is done on pediatric-specific medications.

The market for pediatric drugs, especially those for diseases such as childhood cancer, is relatively small compared with the market for adult drugs because fewer children develop rare and serious illnesses.

To maximize efficacy and return on investment, pharmaceutical companies tend to focus their efforts on therapeutics that address illnesses common to larger populations. This practice forces pediatric specialists to prescribe many medications for children “off-label.” Research, however, has shown repeatedly that drugs and devices for adults can affect children differently, and drugs that are designed for adults sometimes do not work in childhood diseases, or vice versa. For example, a National Cancer Institute-funded team is aiming to test a certain class of drugs against Ewing’s sarcoma, which can occur any time during childhood and young adulthood, but usually develops during puberty, when bones are growing rapidly. But no manufacturers have yet agreed to provide the medications because the drugs are not showing enough promise in more common adult cancers.

Creating Hope Act

The Creating Hope Act is bipartisan legislation that builds on the FDA Amendments Act of 2007, which originally established a voucher for drug development for neglected tropical diseases.

When introducing the legislation, Casey said: “Millions of Americans are affected by rare diseases and neglected conditions for which there is currently no hope because there is no treatment. The Creating Hope Act provides an incentive, at no cost to taxpayers, to develop treatments for these illnesses. The broad support for this legislation speaks to the need to solve this problem.”

The priority review voucher program would award a voucher to a company that gains FDA approval for a new drug application designed for a rare pediatric disease. To be eligible for a priority review voucher, the new drug application for the rare pediatric disease must be:

• Eligible for priority review by the FDA;
• A new drug that has not been previously approved by the FDA;
• For a pediatric indication; and
• For a disease that has received Orphan Disease Act designation.

The Orphan Drug Act was lobbied for by National Organization for Rare Disorders (NORD) and provides incentives for researching and developing treatments for rare or “orphan” diseases. The Creating Hope Act defines orphan diseases similarly to the Orphan Disease Act, in that the disease should affect fewer than 200,000 people. The numbers necessary to be considered a rare disease vary from region to region, but a disease with an incidence of one of 1,500 to 2,500 is typically deemed an orphan disease.

The 2011 version of the legislation is co-sponsored by Sens. Scott Brown, R-Mass., Sherrod Brown, D-Ohio, Al Franken, D-Minn., and Johnny Isakson, R-Ga.

“Since many of these diseases are genetic, more than half of the patients affected by rare diseases are children,” Mary Dunkle, spokeswoman for NORD, told Infectious Diseases in Children. “Very often, these are life-long and serious diseases, which create real challenges for families and the doctors that care for them. So this Act is an important measure that makes good use of existing resources.”

The Creating Hope Act of 2011 fixes certain weaknesses in the current law, such as the limited transferability of the vouchers and an undue waiting period before exercise of the vouchers, which has resulted in minimal use of the current priority review voucher program, according to Nancy Goodman, a parent from Washington, D.C., who is the driving force behind the Act. She founded Kids v Cancer after the death of her son, Jacob, from medulloblastoma.

“Two weeks after Jacob’s diagnosis, his physicians had evidence that the recommended protocol was unlikely to control his tumors. However, they did not modify his treatment because there were no other viable options,” Goodman said in an interview. “In the past 30 years, treatment for medulloblastoma has not materially changed.”

Goodman, who received her master’s in public policy at Harvard Kennedy School of Government and graduated from the University of Chicago Law School, said during the past 20 years, the FDA has had only one initial FDA approval for a childhood cancer drug. Nearly all chemotherapies used for children’s cancers are more than 40 years old.

More incentives needed

Although the legislation is being lauded by several grassroots organizations and by several members of Congress, some said the Creating Hope Act does not go far enough to stimulate research into the pediatric market.

More pharmaceutical companies are finding that work on investigational drug candidates is being delayed or halted in late stages of development because of increasing demands from the FDA for more stringent clinical documentation. Also, more financial backing is needed to conduct this type of research, but with recent cuts, that money is not likely to appear soon.

Steve Projan, PhD, who is senior vice president of research and development at MedImmune, told Infectious Diseases in Children that conservative estimates put the price tag for developing a new drug at $300 million to $600 million, but these costs can easily surpass $1 billion when additional trials are required for approval and for post-marketing commitments.

“Twenty-four percent of (the US) population is made up of children, yet only 11% of the funding coming out of the NIH is focused on children,” Projan said. “[Acts like these] are the government’s way of looking for solutions that don’t require them to spend any money.

“It helps knowing you wouldn’t have to hold your breath for another year to see if you got approval,” he said, adding that exclusivity rights that “make sense” would stimulate research.

Because of the long development process unique to the pharmaceutical industry, Projan said researchers who work to develop new antimicrobials do not have their intellectual property protected the same way as inventors in other industries. For example, 12 years passed from the time tigecycline (Tygacil, Wyeth Pharmaceuticals) was discovered in 1993 to the time it became commercially available. Between 2000 and 2005, Wyeth spent $12.5 million in research and development. In the case of tigecycline, more than 50% of the patent life had expired before the drug became commercially available. Projan said adjusting the standard 20-year patent life for new drugs or offering longer periods of market exclusivity may be a reasonable way to reinvigorate an industry with limited options.

Increased research

Although the government grapples with the best way to incentivize more research into pediatric medications, research continues to lag.

The antibiotic pipeline remains slim, and there are hundreds of diseases for which there are little therapeutic options. All parties said they agree that the Creating Hope Act is a good first step in providing additional therapeutic options.

And other signs of research into specialized areas are also on the horizon. The NIH recently announced plans to establish a registry and center that would examine genetic roles in usable therapies. During a recent meeting with NIH, international researchers from the International Rare Diseases Research Consortium crafted a statement that asks companies to deliver diagnostic tests and 200 new therapies for patients affected by rare diseases by 2020.

Goodman said many members of Congress have expressed interest in hearing from physicians, researchers and biotech and pharmaceutical executives about this legislation. Any readers interested in providing advocacy support for passage of the Creating Hope Act are encouraged to contact her at nancygoodman@kidsvcancer.org. – by Colleen Zacharyczuk

For more information:

• www.kidsvcancer.org/about-us/act-now/
• Connor E. Sci Transl Med. 2011;3:66cm1.

Disclosures: Dr. Connor currently serves as a part-time chief medical officer at 3-V Biosciences and is on the board of directors of ReveraGen Biopharma. He has served as an adviser to Teva and AVI Biopharma in the past year. Approximately 2 years ago, he served as a consultant to MedImmune. Dr. Cure is a LEAP Scholar at Children’s National Medical Center and is funded by the Florence Nesh Charitable Trust through the PNC Foundation. Dr. Projan is senior vice president of research and development of MedImmune.

What areas of research do you feel would benefit most by Creating Hope?

I commend Sen. Casey and his colleagues for introducing the Creating Hope Act. Almost all of the chemotherapeutic drugs we use today to treat children with cancer were approved more than 40 years ago. Although we have leveraged these drugs to dramatically increase the cure rates for children, this approach has come at a price. There are both significant short- and long-term consequences associated with current treatment, and cancer, nonetheless, remains the primary cause of disease-related death in children. This act would provide an important new incentive to better engage scientists and drug development expertise that resides in the biopharmaceutical industry, enabling us to develop more effective and less toxic drugs to treat the children we care for.

Peter C. Adamson, MD, is Chair of the Children’s Oncology Group at The Children’s Hospital of Philadelphia.

Legislators and funding agencies should not only encourage the biopharmaceutical industry to support pediatric studies, they need to encourage pediatric research by providing direct support for collaborative networks of children’s hospitals. To participate in some national collaborative groups aimed at reducing pediatric harm, children’s hospitals are sometimes charged a fee to offset costs. The fees are well worth the benefits, but in this budget-conscious climate, they are disincentives for participation.

The best use of new antibiotics is definitely an important area of research that needs to be looked at in a pediatric-specific manner. It is important to understand in children whether new antibiotics are safe to use and to define the optimal dosing regimens. Pharmaceutical companies can help with these studies. In addition, we need independent studies to help us understand how and when to use new antibiotics in children. We do not want overuse new antibiotics.

Charles B. Foster, MD, is with Cleveland Clinic Children’s Hospital. Dr. Foster recently co-authored an editorial in the Journal of the American Medical Association that calls for pediatric-specific quality measures to guide infection prevention and treatment practices.

Disclosures:Drs. Adamson and Foster report no relevant financial disclosures.