Pediatric oncology research legislation to take effect – OutSourcing-Pharma.com

While the Research to Accelerate Cures and Equity (RACE) Acta measure designed to promote pediatric cancer research and development of therapieswas enacted three years ago, it takes effect August 18. Even with the long lead time, many research entities may find themselves unprepared for the changes.

Outsourcing-Pharma (OSP) discussed the RACE Act with representatives from contract research organization (CRO) PRA Health Sciences:

The experts shared the reasons for the legislation, as well as advice on how sites, sponsors and partners can better prepare for the impending requirements.

OSP: Could you please provide an overview of yourperspectiveon the RACEAct?

PRA: TheResearch to Accelerate Cures and Equity (RACE)for Children Actshould result inmore precision medicine clinical trial options to offer young cancer patients and their families, andultimatelymore pediatric oncology drugs in the pipelinethat willresultinimproved therapeutic outcomes and decreased long-term side effects.This will be achievedby way oftwo notablechanges tothe existingPREA(Pediatric Research Equity Act)as outlined below.In essence,the RACE for Children Actdoes two things:

OSP: In particular, what are the most notable changes between this and the PREA?

PRA TheRACE for Children Act was signed into law as Title V of the FDA Reauthorization Act to amend the PREA (21 U.S. Code 355c) on August 18, 2017 and goes into effect on August 18, 2020. It will impact all cancer drug development. Under the RACE for Children Act, new molecularly targeted compounds for adult cancers will need to be evaluated for childrens cancers if the molecular target or mechanism of action (MoA) of the drug is relevant to the growth or progression of pediatric cancer.

The RACE for Children Act amends the existing PREAandends the previous exemption from PREA requirements for cancer drugs that have orphandrugstatus. Any new drug application (NDA) or biologics license application (BLA) submitted on or after August 18, 2020 for a new active ingredient, dosage form, dosing regimen, or route of administration,unless an exemption of this requirement was provided, must have an agreed initial pediatric study plan before submission.

Put simply, it will be standard practice for oncology drug applications to contain reports of molecularly targeted pediatric cancer investigations (unless a deferral or waiver of that requirement is granted).

OSP: In general, how has the field of pediatric oncology research, and development of treatments, evolved in recent yearsor has it remained relatively flat?

PRA: It has been almost completely flat, especially in comparison to the improvement seen for conditions and diagnoses in other therapeutic areas since PREA came into effect. Wed like to say we are optimists and thatimprovement has been seen, especially with the upcoming implementation oftheRACE for Children Act; however, we knowthere are some startling statistics in the field of pediatric oncology.

Currently,only 4% of the billions of dollars that are spent annually on cancer researchin the U.S.are directed toward childhood cancer(National Pediatric Cancer Foundation),and that of the many drugstheFDA approved for cancer treatment inadults, only 30have been approved for children (June, 2020 FDA website). Thisis despitethe impact thatPREA has had inencouragingan increase in treatments forothertherapeutic areasand indications.

Due to these discouraging statistics, the dire need to increasenot just available but up-to-date treatment options for children became evident. Doing so maygivesome patients with extremely poor or fatal diagnosis hope, andin the endmayalsolessen the debilitating late effects due to present cytotoxic therapies that befall too many pediatric cancer survivors even years after initial therapies and when they are considered cured.

Adult oncology has much more widely available molecularly targeted treatment optionswhen compared to pediatric oncology.We need to start uniformly applying the advanced science of molecular targeted therapies to our children.

OSP: Could you share your perspective on how those changes might be beneficial, or possibly negatively impact, various stakeholders?

PRA: PRA considers patients the most vital stakeholdersin clinical development.We cant forget whothe why is inthe tireless work we do.PRA knows that many patientadvocacygroups have worked tirelesslyin the preceding years tohavetheir concerns and voices heard andhave brought usto where we are today with the RACE for Children Act.

Sponsors the drug companieshavea lot to learn regarding this updated legislation and how it will impact their drug development.Each appropriate drug will have to be doubly considered and applied for adults and pediatrics.This should be perceived as a positive for patients, families, investigators/sites, and the public.

However, sponsors may well perceive this asan additional hurdle, primarily due to the burden to conduct the trialswhen there may be little return on investment.Obviously, sponsors wouldbe happy to contribute to the improvement of treatments for children, butrealistically there must be a return oninvestment,and thisis not easily doneaccording to traditional business models.

We all need to worksmartlyto lower burden and cost for all stakeholders.With collaborative efforts, what has not been perceived as asignificantrevenue generator for drug companiesdue tothe rarity ofchildhood cancersmaybecomesowhencancer ismore appropriatelytreated as a molecular diseasewithinnovative approaches.

The need for collaborationbetween all stakeholdersto make the RACE forChildren Act a success isthuscritical, and this maybeseen asa challenge for some, at least initially.

OSP: You mentioned the changes could cause a scramble to develop pediatric study planscould you please elaborate?

PRA: Its all about timing.Planning ahead can be enormously helpful and sponsors should never assume anything.The FDA requires there be an agreed uponiPSPwhen sponsors submit their marketing authorization for a drug that includes a new active ingredient, new indication, new dosage form, new dosing regimen,or new route of administration.

Previously,many of these pediatric oncology drugs were exempt from PREA.TheRACE for Children Act changes that and we expect far fewer exemptions.Once aniPSPis submitted,it cantakeseveral months for it to become agreed upon by the FDA. If the FDAdoesnt agreewith it the first time, more time ensues.

The total length for review of aniPSPcan be aslong as210 days.TheiPSPshould be initiated after the End of Phase 2 (EOP2) meeting, and many sponsors may not have this expertise in-house.

While before sponsors reasonably expected to receive a waiver, they can no longer count on that.Given the focus and commitment of the FDA to increase therapeutic options for pediatric oncology,and the time and expertise required for developing a pediatric plan,iPSPsshould be planned for in advance to prevent alast-minutescramble.

OSP: How has PRA been readying its operation and preparing to help its clients and others for the RACE Act?

PRA: Here at PRA, we have been preparing for the RACE for Children Act since it was passed in 2017, so we are able to quickly and effectively support our clients and sponsors looking to conduct this research. We have brought together a highly credentialed and cross-functional team internally, including27board certified pediatriciansand nineboard certifiedpediatriconcologists/hematologists,to serve as hands-on consultants in the development and execution of pediatric study plansand trial conduct.

OSP: How will thosechangesimpact pharma companies and their research partners?

PRA: Weve tried to think of everything and continue to communicate about all the possibilities of the RACE for Children Act.We too want this new, updated legislation to go forward as smoothly as possible and with the final intent,as the FDA has stated,ofbringingmore pediatric oncology drugs into the pipelineandtopatients.

However,we also want to bemindful that were notjust bringingmore pediatric oncology drugs intothe pipeline, but appropriate ones. Due to the rarity of pediatric cancer, there may be timeswhencertaindrugs and trials will need to be prioritized; we recognize that and will help to ensure that not only will there be moretrials, but the right trials for pediatric cancer.

Companies and research partners will need to embracecollaborationwith each other, sites, and patient representatives. With the significant oncology pipeline but the paucity of pediatric patients, innovation and collaboration will be critical, starting in the pre-competitive space (for example, pre-clinical data and tissue repositories).

Master protocols, innovative study designs, and global studies will become more common. This requires scientific and drug development expertiseand awareness of ongoing regulatory and technological developments.

OSP: Is there anything else youd like to add that I havent touched upon?

PRA: Looking back at the previous question, we ask ourselves, what are the best trials for pediatric cancer research to focus on?If your child is diagnosed with cancer and given a 90% cure rate,unfortunately,thatstatisticdoesntmatter if your child falls into the 10% that isntinitiallycured or,worse yet,doesnt survive.During that time, your child is the only thing that matters.

Whatwe do know about pediatric cancer therapy today is that of those that do survive,nearly 80% will have some significant late effect,likelyyears later, directly related to their childhood cancer therapy. Many will even get a secondary cancer as an adult related totheirinitial therapy.

Forsomediagnoses,such as diffuse intrinsic pontine glioma, there is no cure and families are told there may be up to an18-monthlife expectancy.Thereis so much room to do better.

Similarly,PRA is embracing human-centricity, and just as we say that it takes a village to raise a child, it will takeavillage to commit to curing a childofcancer.

Child death is unacceptable, and the RACE for Children Act is essentially closing a loophole (orphan exemption) and leading the scientific way for oncology to be addressed as a disease with molecular targets, not organs/tumors. We must remove the barriers for sponsors and others to show that treating pediatric cancer is not a burden,but a responsibility, and if done well with the help of PRA it will be profitable.

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