The prominent foundation — the richest nonprofit seeking to cure the crippling neurological disorder — initially wanted to collaborate on a study with the Georgetown University researcher. His preliminary findings last year had buoyed patients’ hopes for the first Parkinson’s medicine that might reverse some of their debilitating symptoms.
The trial was supposed to begin in October, but Fox and the Georgetown team had a bitter falling out, and it’s unclear whether Georgetown will be able to obtain the medicine from its manufacturer so that the study can proceed. Fox, meanwhile, is moving forward on its own, and has established a separate group to study the same drug. That trial won’t start until about a year from now — a long wait for millions of Parkinson’s patients worldwide.
“We thought it was a scientific discussion, but (the foundation) had alternate motives,” Dr. Charbel Moussa, the Georgetown scientist, told STAT. Fox engaged in “a premeditated attempt to cut us out,” he said. “Some people think they are the owners of the conversation, the owners of the scientific debate, the owners of Parkinson’s research.”
Todd Sherer, chief executive of Fox, denied Moussa’s accusations. “We acted in good faith” to reach an agreement with Georgetown, he said, noting that the foundation has a long record of “credibility and authority” in its collaborations with hundreds of researchers.
STAT learned of the dispute from members of the Parkinson’s research community, and subsequently examined published scientific papers and emails and research proposals that passed between Georgetown, Fox, and the foundation’s collaborators.
Conflicts over credit and control of research are far from rare in the chase for medical breakthroughs. But rarely do such fights — with high stakes for professional stature, organizational prestige, and fundraising — erupt into public view.
The trial offers Moussa, a little-known scientist, a chance to vault into the top ranks of researchers, while Fox and its collaborators could reinforce their standing and tap into a bonanza of donations from wealthy philanthropists and worried patients.
The episode also highlights the tension between scientists and foundations that are no longer content simply to dole out money. Following the lead of the colossal Bill & Melinda Gates Foundation, major medical research philanthropies increasingly seek to coordinate or manage studies, or control details of how they are done — vexing many grant recipients.
In this case, the clash involves nilotinib, a cancer drug tested by Moussa and his colleagues in 12 Parkinson’s patients — many of whom described substantial relief from symptoms such as shuffling gait and cognitive decline. Although the trial was small, the results announced last year thrilled doctors and patients who have waited decades for a glimmer of success.
Soon after, Moussa said, the foundation, started by actor and Parkinson’s patient Michael J. Fox, approached him about funding his next steps. Moussa said he already had separate funding, and approval from the US Food and Drug Administration and a university research review board to conduct a Phase 2 trial — a larger test of the drug’s safety and effectiveness — at Georgetown. He hoped that Fox would underwrite costs for other test locations, which would give the results more credibility.
Discussions between the sides lasted about six months, during which Fox officials reviewed and asked for changes in the Georgetown study design. Moussa disagreed with some requests involving verification of concepts he said had been demonstrated in the initial study. The modifications would “delay us for one year, and this was not good for patients,” Moussa said.
The talks fell apart when Brian Fiske, the foundation’s senior vice president for research, told Novartis, nilotinib’s maker, that Fox disavowed the Georgetown project.
“Whether they [Novartis] will continue to review your proposal is of course up to Novartis, but we made it clear that this was submitted without our knowledge or commitment to support,” he wrote to Moussa in a June 17 email provided to STAT by the Georgetown scientist.
Moussa said he hopes Novartis eventually will donate the drug — valued at several million dollars — for the proposed 75-patient trial. He said Fiske’s intervention seemed designed to sabotage his proposal.
Soon after, Fox announced its own Phase 2 trial. Sherer said he encouraged Novartis to supply nilotinib to all researchers — including his foundation and its partners from two other nonprofits.
Novartis spokeswoman Julie Masow would say only that the company “is in discussions with Georgetown about the possibility of supporting this study.”
Sherer said Fox contacted Novartis because Moussa told the drug maker that the foundation was funding his work before an agreement was final. Moussa called that characterization “completely false.” He said he now thinks Fox had planned for some time to delay Georgetown’s efforts, to give its own trial a lead in the race to prove nilotinib’s value.
“The reason why it’s so hard-fought is that there are some people who believe that this is the drug that could be the first to demonstrate an ability to slow the progress of Parkinson’s disease,” a potentially towering achievement, said Peter Schmidt, senior vice president of the National Parkinson Foundation, a smaller charity that also funds research.
Beyond the finger-pointing, there are real scientific differences about how to construct the best test of nilotinib.
“There are people who believe that a better-run trial might demonstrate positive findings. Thus, there are good and noble reasons for a funding agency to want to be involved in organizing an important trial,” Schmidt said. He offered the historical example of the National Foundation for Infantile Paralysis (later, called March of Dimes), which pulled control of the final polio vaccine trial from its inventor, Jonas Salk, in favor of a different leader.
But Schmidt cautioned against unnecessary delays of a Phase 2 trial. “The question of whether or not nilotinib will make a difference is one of great urgency to people with Parkinson’s today,” he said. “Anything that slows down getting the answer to that question is hurting patients.”
The dominant player
Michael J. Fox’s star power has built the foundation into a fundraising juggernaut. Rather than directing scientific programs, he focuses on boosting public awareness and donations — assisted by fellow celebrities, such as Tina Fey, Paul Simon, and Julianna Margulies, with whom Fox starred on “The Good Wife.” Moguls from Silicon Valley, rather than Hollywood, have given the most, including $25 million or more in annual contributions from Google cofounder Sergey Brin and his ex-wife, 23andMe founder Anne Wojcicki.
The foundation awarded nearly $88 million in research grants last year, dwarfing combined support by all other Parkinson’s nonprofits. Fox has gained far-reaching influence by funding leading academic, corporate, and even National Institutes of Health researchers.
Sherer, 43, joined the foundation in 2004 after completing a PhD in neuroscience and postdoctoral training. He built the foundation’s scientific team that assesses and steers research priorities before being elevated to CEO in 2011. In a news release at the time, Michael J. Fox praised Sherer’s “uncommon ability to look at therapeutic progress from both the scientist and the patient perspectives,” and how “his research peers … willingly follow him in new and challenging directions.”
Since Sherer took the top job,the foundation has funded about 1,000 grants. Most were calculated to the dollar, akin to contract invoices and unlike conventional grants awarded for a body of work or project. Fox spokeswoman Christina Brdey said grant managers approve specific research budgets and approaches.
“Philanthropies find that this kind of contract research is acceptable to researchers, given the difficulty in securing federal funds,” Schmidt said.
Allan Tobin, director emeritus of the UCLA Brain Research Institute, helped start the CHDI Foundation, which funds studies on Huntington’s disease, another neurodegenerative disorder. He said CHDI also actively shaped grantee projects to help ensure the best results.
This hands-on approach is ascending in medical research philanthropy, Tobin said, and on the whole works well, although “some CHDI-supported researchers objected to the foundation’s scientific and financial management.”
Fox sometimes parses large projects into many grants, maintaining overall control, as it has done for a large observational study to define physical or biological signs of Parkinson’s. Working with the study’s principal investigator, Fox officials manage “the study’s protocol, governance, financing, expansion, promotion, (and) recruitment,” Brdey said in an email.
Fox is spreading $60 million over dozens of testing sites and research programs for that project. Brdey compared the foundation’s role to that played by the National Institute on Aging on a similar Alzheimer’s project.
Leading a trial for the most important Parkinson’s treatment in more than 40 years could bring the Fox Foundation valuable cachet and more donations, according to executives of other philanthropies.
“The March of Dimes took advantage of their direct involvement in the development of the polio vaccine to continue as a fundraising powerhouse, despite having achieved their principal mission objective with the vaccine,” Schmidt said in an email. “It is very powerful to be able to say to a prospective donor, ‘We are doing this,’ rather than, ‘We are funding this.’”
Decades of frustration
Parkinson’s afflicts about 1 million Americans, who face increasing tremors, stiffness, movement problems, and often mental decline. It has no cure. Parkinson’s is associated with a reduced supply of dopamine — a naturally occurring chemical in the brain that helps nerve cells talk to each other.
Since the 1970s, to relieve some movement symptoms, many patients have taken levodopa, also called L-dopa, which replenishes dopamine. But L-dopa does not reverse the course of the disease and helps less over time, so scientists have long sought alternatives.
Nilotinib, a blood cancer medicine, has long been considered for its potential to help Parkinson’s patients. Lab and animal studies suggested that the drug could protect dopamine-producing cells in people. But its toxicity made researchers nervous. It carries the Food and Drug Administration’s “black box warning” — indicating possibly life-threatening side effects.
Georgetown scientists, who had been deeply involved in basic research exploring nilotinib’s potential, felt confident that a small human safety trial at far lower doses than used by cancer patients would be safe to try.
Their results, presented at a meeting last October of the Society for Neuroscience, exceeded every expectation.
Nilotinib appeared to double patients’ dopamine production, reduce the death of dopamine-producing nerve cells, and clear from those cells a toxic protein associated with Parkinson’s and a related disorder, dementia with Lewy bodies.
Relief from symptoms seemed equally striking among the 11 patients who completed the trial. Alan Hoffman, 75, a retired university professor who participated in the trial, said in an interview that by 2014, his Parkinson’s had become devastating. He suffered frequent falls and stiff, “frozen” muscles. After a life of intellectual curiosity, his powers of concentration were reduced to scanning news headlines.
Nilotinib proved transformative, Hoffman wrote in his blog. “I was walking steadily. … My speech was louder and clearer, I was no longer falling, I was less confused about things in general, and my life was considerably better,” he said. “I first read the David McCullough book on the Wright Brothers and then progressed to others. I was thrilled!”
When the study ended, Hoffman regressed sharply, he told STAT. After he secured nilotinib from Canada at a discount from the $10,000 monthly cost charged in the United States, his symptoms again began to taper off.
Such stories prompted doctors around the world to begin prescribing the drug for some of their Parkinson’s patients, though it had not been approved or proven safe and effective for that condition.
A few participants in Georgetown’s Phase 1 safety trial experienced health problems that might have been caused by nilotinib, and the study had serious limits — no control group or double-blind design, in which neither patients nor researchers know who gets the drug and who gets a sugar pill. Such features can help verify benefits attributed to nilotinib and possible side effects. Moussa and his colleagues cautioned that the hopeful results must be confirmed in a larger Phase 2 trial.
Quest for collaboration
Moussa, 43, said he acquired his love of science and medicine by accompanying his father, a large-animal veterinarian, on his rounds to farms in their native Lebanon. He earned his MD and PhD degrees in Australia, and came to Georgetown in 2003.
“Since my first year in college, it always fascinated me how the brain works. But there are few answers,” he said. “Neuroscience is one of the areas in medicine today where you can really make a contribution.”
Fox had rejected his request to underwrite the Phase 1 nilotinib trial. “So when we announced the results and Michael J. Fox Foundation contacted me, it was an exciting moment” and validation, he said.
Moussa confidentially shared his group’s test plans, proposal to Novartis, and other details. Both sides expected Fox to provide funds.
Moussa provided STAT a February email from Fox research director Marco Baptista, who wrote, “MJFF is willing to work with you to design such a study and fund it. … I can ensure you that I have the full support of MJFF senior management to overcome any obstacles so that together we can make this happen.”
Dr. Patrik Brundin, a top scientist at the Van Andel Research Institute in Michigan, and Dr. Richard Wyse, research director at the United Kingdom-based Cure Parkinson’s Trust, also approached Georgetown about possible collaborations. In an email, Wyse praised Moussa for convincing top global experts that low-dose nilotinib was “likely to be safe” for Parkinson’s patients.
But talks between Moussa and the possible collaborators foundered in June after he learned that Fox officials had approached Novartis about Georgetown’s proposal behind his back. Those officials also pressured Moussa not to speak with Novartis independently. Fiske, the Fox vice president, wrote in an email that Moussa should only have submitted to Novartis a proposal approved by the foundation, a process the foundation thought Georgetown had agreed to follow.
Moussa bristled at Fiske’s admonition. “Your email appears to suggest that you are in control of our study,” Moussa replied. “We do not feel that we have to wait for your approval to continue our engagement with Novartis. We have come a very long way to get the drug donated and we are interested in engaging MJFF for funding. We do not believe that one thing depends on the other in any way, shape, or form.”
Fiske responded that “given these challenges” in communications with Novartis, the foundation was “reassessing the ability of MJFF and Georgetown to continue our collaboration and are reviewing other options we have for independently evaluating nilotinib.”
In interviews, Brundin and Sherer described their differences with Georgetown as technical ones concerning study design and priorities for the Phase 2 trial.
Moussa said Fox officials never formally notified him that his grant proposal had been rejected. In July, he published the results of the initial trial in the Journal of Parkinson’s Disease, which is co-edited by Brundin. The article appeared alongside an editorial by Brundin, Wyse, and Sherer, which said the Georgetown study “substantiates a new direction” but castigated the intense media exposure when the results were announced last fall as “an object lesson on how not to report a small clinical trial that has no placebo control.”
The editorial concluded that a new clinical trial of nilotinib was warranted and that it should involve “leaders in (Parkinson’s) clinical trial design” and be conducted at multiple sites.
Moussa read the editorial as an attempt to disparage his group’s work and planned trial. Without Fox’s funding, it would be conducted at only one site.
The commentary made no mention about what the authors were planning next.
A gatekeeper moment
The same day the editorial appeared, the three authors announced in an optimistic press release their mutual collaboration on a multisite, Phase 2 nilotinib trial.
Moussa said he had no idea it was coming. “This is a huge endorsement of what we are doing at Georgetown University, but why they would want to … cut us out of the process, I don’t understand,” he said. “Now they are racing us to get the credit.”
Brundin said he didn’t understand such concerns. If nilotinib does become important, he said, most credit would go to basic scientists who uncovered its potential. That includes Moussa, who “ironically, would benefit tremendously if there is a second trial (unconnected to Georgetown) that shows nilotinib works, because it will have so much more credibility…” Brundin said.
Georgetown has applied for a patent, with Moussa as inventor, on using nilotinib to treat neurological disorders, and could earn licensing fees should the medicine be approved for that use.
Moussa contends that Brundin, Wyse, and the Fox Foundation improperly took advantage of their access to confidential materials about his research to plan their own study. This included prepublication versions of Georgetown’s journal article, detailed plans for his Phase 2 study, and his proposal to Novartis that showed the scientific explanation for the drug donation request. For months, Moussa said, Fox “wanted to get more data out of me.”
Sherer and Brundin said nothing improper occurred. Their own study plan, Brundin said, was based on “publicly available scientific reports, including (Georgetown’s) own report, which is published, of course, in the journal.”
Leigh Turner, a bioethics professor at the University of Minnesota, said that in general, funders and journal editors should exercise care to be above reproach in their handling of insider information.
“You have these gatekeeper moments, where it is possible to take advantage of positions like that, to gobble up as much information as possible, and repurpose it for your own advantage,” he said.