Executive Summary

Blue ribbon panel has plenty of industry-friendly recommendations on ways to accelerate oncology science, but with the clock ticking down on the Obama Administration, the question is whether the recommendations have any political traction.

Recommendations from Vice President Joe Biden’s Cancer “Moonshot” Blue Ribbon Panel have a specific emphasis on patient-focused research, new areas for oncology R&D and the establishment of a national clinical trial data network for “one-stop, free access” to patient data from studies across the country.

The Blue Ribbon Panel was established to identify key scientific opportunities to meet the Moonshot’s ambitious directive: to make a decade’s worth of progress in preventing, diagnosing and treating cancer in five years. (Also see “Biden’s Cancer Initiative May Intensify Industry, Government Collaboration” – Pink Sheet, 18 Jan, 2016.)

The moonshot report, released Sept. 8, lists 10 recommendations that cut across all areas of oncology: developing a patient-level understanding of the disease, improved access to clinical trials, new research to better understand the causes of different types of cancers, improved prevention strategies and methods to avoid drug resistance.

For manufacturers, the recommendations are all upside: early research encouraged by the Cancer Moonshot could open up new areas for drug development. Pediatric indications are particularly highlighted as a necessary focus of new research, and the report also has a specific emphasis on immunotherapy and the development of more targeted diagnostics and devices.

More Collaboration Wanted

In immunotherapy, current investments – led by companies like Merck & Co. Inc. and Bristol-Myers Squibb Co. – “represent only the tip of the iceberg of what is possible,” the report says. A Cancer Immunotherapy Clinical Trials Network would coordinate research efforts and provide a “national infrastructure” to efficiently discover and evaluate novel immune-based approaches to cancer.

The panel also recommends additional R&D investment to better understand oncoproteins, which are significant drivers of pediatric cancers. A more collaborative effort could lead to the development of novel small molecule probe compounds and “galvanize” investment in pediatric cancers by “lowering the barriers to success,” the report says.

A third pro-innovation recommendation would create incentives for manufacturers and researchers to develop “powerful new technologies” to deliver “smarter, more effective therapies tailored to patients’ individual tumors.” The report notes recent success in using devices in animal models to deliver micro-doses of drugs directly into a tumor. A proposed demonstration project would simultaneously test several new drug candidates in a single tumor.

A recommendation on research efforts to identify “effective, sustainable strategies” on cancer prevention repeatedly mentioned the success of human papillomavirus vaccines at preventing cervical cancer. But the report also notes that uptake of the HPV vaccines marketed by GlaxoSmithKline PLC (Cervarix) and Merck (Gardasil) has been hampered by concerns about side effects and a perceived relationship about vaccination and promiscuity. Moonshot funding would increase awareness of cancer prevention techniques; HPV would be a “high priority” cancer on that list. (See table at bottom of article for a complete list of all 10 recommendations.)

213 Appearances

A central theme of the report is a need for direct patient engagement in oncology research – patient-focused recommendations include individual tumor profiling, pre-registration for clinical trials, use of patient-reported outcomes and evidence-based symptom management.

The patient focus of the report’s recommendations should be expected: the Cancer Moonshot itself was introduced as an extension of President Obama’s Precision Medicine initiative, and the task force is chaired by Greg Simon, a cancer survivor and former president of the patient advocacy group FasterCures. (Also see “Cancer Moonshot Initiative: FDA To Form Virtual Oncology Center of Excellence” – Pink Sheet, 1 Feb, 2016.)

Indeed, “patient” appeared 213 times in the 72-page report.

Regulatory Issues Outside The Scope

The report did not make any mention of the creation of an Oncology “Center of Excellence” at the Food & Drug Administration. The creation of a Center of Excellence was included as part of the overall Moonshot initiative, but the Blue Ribbon Panel was specifically charged with identifying scientific opportunities in oncology, so any changes to the regulatory environment would be outside its scope.

Implementation of an Oncology Center of Excellence at FDA is already underway; the creation of OCE was announced in conjunction with Biden’s “Moonshot” Summit at Howard University in late June. FDA’s Office of Hematology & Oncology Drug Products Director Richard Pazdur, MD, was selected to head OCE. (Also see “FDA’s Pazdur Won’t Become Oncology Bureaucrat: ‘My Presence Will Be Felt'” – Pink Sheet, 30 Jun, 2016.)

The need for regulatory reforms, however, is a topic for consideration by the larger Cancer Moonshot task force, which is made up of representatives from the heads of many federal agencies, including FDA and the Department of Health & Human Services. Among other areas, the task force has been charged with identifying “unnecessary regulatory barriers” and “ways to expedite administrative reforms.” Those findings and recommendations are due before December 31, 2016 – in the waning days of the Obama Administration.

Pricing Totally Off The List

The report also identified a number of policy issues that were outside the scope of the panel, but that members felt would need to be addressed before many of the recommendations can be implemented. Seven issues have been forwarded to the Cancer Moonshot task force for consideration; notably, while “coverage and reimbursement” made the list, drug pricing did not:

• Coverage and reimbursement
• Privacy and consent with regard to patient data
• Fragmentation of the delivery of patient care in the community
• The need to improve the clinical trials system
• Incentives to encourage pediatric drug development
• New federal research funding models
• Barriers to data sharing

Working Against The Clock

The Blue Ribbon Panel was also working against the clock; the panel took just five months to make its recommendations. The question now is which, if any, of the recommendations will be implemented by the next administration. Hillary Clinton has pledged to continue the work of the Cancer Moonshot if elected to the White House; Donald Trump has not taken a position on the Obama/Biden Administration initiative.

The Blue Ribbon Panel conducted its work on an accelerated timeline: members were announced April 4 and the first (virtual) meeting was held April 11. Much of the work was done by seven working groups, which included additional outside members. The working groups were announced May 2 and met frequently until mid-July. The Blue Ribbon Panel itself met several more times – in person on April 18 and July 20, and virtually on July 13.

The majority of the 28-member panel hails from the top research universities and hospitals in the country. The acting deputy director of the National Cancer Institute, Dinah Singer, PhD, is the sole government official on the panel; ex officio members include FDA Commissioner Robert Califf, MD. Ellen Sigal, PhD, the founder and chair of the patient advocacy organization Friends of Cancer Research, is also a member of the panel.

The one pharma industry spot on the Blue Ribbon Panel was filled by Pfizer Worldwide R&D President Mikael Dolsten, MD, PhD. NantWorks CEO Patrick Soon-Shiong, MD – who founded Abraxis BioScience and developed the cancer drug Abraxane, before selling the company to Celgene in 2010 – also served on the panel. Both executives, while obvious choices for the panel, were also a bit controversial at the time of their appointments. (Also see “Cancer “Moonshot” Launch Team Announced: Uncomfortable Ties To Anti-Industry Headlines” – Pink Sheet, 13 Apr, 2016.)

Additional industry representatives served in one of the seven working groups. The companies represented were Bristol-Myers Squibb (Alan Korman, PhD), Genentech (Ira Mellman, PhD), Merck Research Labs (Roger Perlmutter, MD, PhD), Incyte Corporation (Peter Langmuir, MD) and Pfizer (Bob Abraham, PhD). From FDA, Office of Oncology Products Director Rick Pazdur, MD, and Lead Medical Officer Marc Theoret, MD and FDA Chief Health Informatics Officer Taha Kass-Hout, MD, also served in working groups.

Recommendations from Vice President Joe Biden’s Cancer ‘Moonshot’ Blue Ribbon Panel

Network for direct patient engagement

Enlist direct patient engagement through a federated network where patients will be offered comprehensive tumor profiling. Many patients are eager to provide their data, and gathering this information in a linked network of databases would enable more precise knowledge about what works, in whom, and in which types of cancer. Providing their data would also “preregister” patients for clinical trials, enabling them or their physician to be contacted if their tumor’s molecular characteristics made them eligible for new clinical trials.

Cancer immunotherapy clinical trials network

Organize a cancer immunotherapy clinical trials network, for both adult and pediatric cancers, that would develop and implement a national strategy to discover and evaluate novel immune-based approaches, with the goal of increasing the cure rate in cancer patients and eventually developing vaccines to prevent cancers of all types.

Therapeutic target identification to overcome drug resistance

Launch interdisciplinary studies to delineate the range of genetic, molecular, cellular, and physiologic mechanisms that lead cancer cells to become resistant to previously effective treatments, with the goal of informing the development and clinical testing of new therapies to prevent or overcome drug resistance and thereby reducing deaths from recurrent disease.

A national cancer data ecosystem for sharing and analysis

Create a National Cancer Data Ecosystem to collect, share, and interconnect a broad array of large datasets so that researchers, clinicians, and patients will be able to both contribute and analyze data, facilitating discovery that will ultimately improve patient care and outcomes.

Fusion oncoproteins in pediatric cancer

Improve our understanding of the abnormal fusion proteins that result from chromosomal translocations and have been found to drive many pediatric cancers. Integral to this is a coordinated research effort that will lead to the creation of new preclinical models of these pediatric cancers, the identification of their key dependencies, and the application of this knowledge to develop novel therapeutic approaches that target their mechanisms of action.

Symptom management research

Support research necessary to accelerate the development of guidelines for routine monitoring and management of patient-reported symptoms in all care settings, throughout the cancer continuum (from diagnosis throughout survivorship and at end-of-life) and tailored to differing patient and survivor needs. Systematically gathered patient-reported outcomes data and evidence-based symptom management are needed to improve patients’ quality of life and the likelihood that they will adhere to effective treatments that are effective rather than abandoning them because of intolerable side effects.

Prevention and early detection: implementation of evidence-based approaches

Conduct implementation science research to accelerate development, testing, and broader adoption of proven cancer strategies to significantly reduce cancer risk and health care disparities. Research should focus on identifying effective, sustainable strategies that involve individuals, families, and caregivers; health care providers and systems; and the greater community. High-priority areas for which much is known about effective prevention and screening modalities are HPV vaccination, colorectal cancer screening, tobacco control, and identification of individuals with genetic predisposition to cancer, both in the general population and among medically underserved groups.

Retrospective analysis of biospecimens from patients treated with standard of care

Analyze acquired tumor samples from thousands of patients who have received standard treatments to develop hypotheses about which tumor features predict clinical benefit, treatment resistance, and other clinical outcomes. Once these categorizations are validated in clinical trials, they can be used to develop better risk stratification of cancers and allow tailored treatments to be developed for patients who are at high risk of relapse or who likely would not benefit from standard of care alone.

Generation of human tumor atlases

Create a dynamic three dimensional map of the evolution of human tumors of all types, pediatric and adult, by documenting the genetic lesions and cellular interactions that guide the development of each tumor as it evolves from a precancerous lesion to advanced cancer while interacting with its microenvironment (including suppressing immune system recognition) to promote tumor growth, metastasis, and development of resistance to treatment. This comprehensive picture of the events and interactions that determine cancer cell behavior will help reveal the processes that underlie cancer, make it possible to predict how cancers will develop and respond to treatment, and enable the identification of new therapies for cancer treatment and new strategies for cancer prevention.

Development of new enabling cancer technologies

Support the development of promising new technologies that will accelerate testing of therapies and characterization of tumors. These include implantable microdosing devices for testing drug effectiveness directly in tumors; new tumor models such as organoids and other patient-derived tissue models that preserve the architecture and range of cell types seen in actual tumors; advanced imaging technologies such as single-cell mass cytometry and multidimensional fluorescence microscopy that allow proteins to be visualized within cells; new patient imaging approaches such as radiologic imaging, nuclear medicine imaging methods using new metabolic probes, and PET imaging using labeled antibodies, as well as methods that allow the results of different imaging technologies to be combined; and computational platforms that allow integration of data derived from these studies.

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