If you saw the mainstream news headlines going into #2018ADA, the biggest diabetes conference of the year, you may have thought we're on the verge of a groundbreaking diabetes cure. That's because the controversial Boston-based researcher Dr. Denise Faustman, who has fueled hope and raised millions of dollars in donations from across the country, began promoting her latest findings in the days before the start of this year's American Diabetes Associations Scientific Sessions in Orlando.

By doing so, there was talk that she may have violated the ADA's embargo policy, which immediately kicked off a heated response from the medical community, creating a somewhat unheard-of blowback against an established researcher.

In an eyebrow-raising move that may be the first of its kind, the ADA and JDRF issued a joint statement cautioning the community to not get too excited about Dr. Faustman's research at this point, noting her study's very small sample size and the fact that "the findings prompt thought-provoking questions but not definitive answers" which are needed before her work can be touted so broadly as a success.

Notably, the ADA also says it's investigating whether Dr. Faustman violated the Scientific Session's embargo policy by pre-publicizing her research and whether she may be banned from future Scientific Sessions.

Whoa!  Leave it to Dr. Faustman to cause a stir like no one else seems to be able to do...

When contacted for a response, Faustman told us the joint statement "came as a little bit of a surprise since we have gone to great efforts to engage both organizations in a positive dialogue."

Many passionate followers in our D-Community have clear opinions on the motivations from each side. Her fans tend to see her as a victim of the big dogs' intolerance for novel approaches, while critics imply that she's a self-promotional fraud peddling false hope.

We've kept tabs on Dr. Faustman's work over the years, from an initial chat in 2009, an update in 2012 and then another interview when her Phase II clinical study was beginning in 2015. Here's a look at background of her work, and the research update that has caused this latest drama...

 

Dr. Faustman's BCG Vaccine Research

For those not familiar with Dr. Faustman's work, she has long been studying something called BCG (Bacillus Calmette Guerin), a generic vaccine that's been around for almost a century and was originally designed to combat tuberculosis (TB). The idea: boosting BCG could stop the pancreas from killing off the beta cells that making insulin, allowing those affected by diabetes to regenerate. Faustman made what was described as a groundbreaking discovery in mice in 2001, but wasn't initially able to replicate that, and her bold promotion of this research kicked off a firestorm of controversy among the medical community and research orgs who doubted her approach. In later years, Faustman points out that other mouse studies did replicate some of her initial findings, but that is up for debate depending on whom you ask.

Share on Pinterest

In her Phase I findings, her team at Massachusetts General Hospital found that in people with "long-term" or "advanced" type 1 diabetes, i.e. having the illness for at least 15-20 years, their vaccine introduced the beginning of pancreatic, insulin-producing cell regeneration.

She finished the first phase of her clinical trials in 2010. She applied for JDRF funding but did not receive a grant, presumably due to doubts about the validity of her work. Mostly because of having to fundraise independently, it took another several years to start the second phase of her research in 2015. That is ongoing and will likely take more years to complete (the estimated clinical trial completion time is 2023, at the moment).

The latest findings published on June 21 are a follow-up on the 9 (yes, nine!) participants enrolled in her original small study eight years ago. It looked at the PWDs' effects over the course of three, five and eight years following the Phase I study.

Study participants' A1Cs dropped slightly and they had "near-normal" BGs, requiring less insulin, and felt free to check their glucose levels less frequently. A1C results went down on average more than 10% during the three years after their treatment and 18% after another year, the study data shows. Participants were also able to reduce insulin intake and achieve "normal" BG levels, the research shows. Interestingly, it appears the vaccine takes a 3-4 years to kick in -- something that Faustman and her team aren't sure why that happens but will continue investigating.

“This is clinical validation of the potential to stably lower blood sugars to near-normal levels with a safe vaccine, even in patients with longstanding disease,” Dr. Faustman said. “In addition to the clinical outcomes, we now have a clear understanding of the mechanisms through which limited BCG vaccine doses can make permanent, beneficial changes to the immune system and lower blood sugars in type 1 diabetes.”

Yet, in the study itself, there's a significant point that Dr. Faustman's research makes that basically contradicts claims from the previous study results -- that the BCG vaccine's A1C and BG-lowering effect is not a result of pancreatic cell regeneration. The paper states: "In the human, this stable blood sugar control was not driven primarily in these human subjects by pancreas recovery or regeneration." In fact, it says that C-peptide regeneation as seen in mice trials weren't replicated in the human PWDs.

Aside from those initial published results, Dr. Faustman also released a "late-breaking" poster on June 23 at the Scientific Sessions, though the data looking at "another subset of patients" was pretty similar to what had been written in the Nature article published days earlier.

 

June Media Blitz

A week before the embargoed research findings were set to go public, Dr. Faustman's team reached out to mainstream media and diabetes press to share some of the new data. So when the ADA conference began, headlines were already appearing across the spectrum -- from Newsweek, Time, STAT, business journals, and diabetes-specific publications with headlines such as "Has Dr. Faustman Found a Cure for Type 1 Diabetes?"

Ugh... If her group is good at anything, it is definitely PR. 

That triggered the response from ADA and JDRF, who rarely collaborate on joint statements unless they believe the issue is fairly monumental.

 

ADA and JDRF's Concerns

On June 25, the two biggest diabetes organizations in the country went public with their concerns by issuing a statement in direct response to all the chatter on Dr. Faustman's research. One might see this move as not only a slap on the hand for a researcher gone rogue, but also a possible warning that PWDs should not keep throwing their money at work that may be creating false hope.

The orgs point out that while this work has attracted attention, Faustman's study only followed a very small number of patients -- nine people at the five-year time point, and three people at the eight-year time point -- "and must be interpreted with caution."

Share on Pinterest

The statement also lists specific limitations that should be considered:

  • All study participants continued to use standard insulin therapy throughout the trial; it’s not a situation whereby the treatment changed their standard of care (all vaccinated individuals remained on insulin therapy).
  • The patients with reported positive outcomes achieved only moderately lower A1Cs, which, while marginally statistically significant, cannot be generalized to the millions of people living with T1D and is not established to be as a result of the vaccination.
  • The research report doesn’t account for the natural variability in A1C levels over time, which is well known to occur in this population: they tend to improve in people with T1D as they age, particularly as they move out of their teens and early 20s. It’s unclear what role that natural history may have played in these subjects.
  • There is no detail on the standard of care in the BCG treated and control group. For example, was the care comparable between both study groups or were adjunctive therapies used?

The statement then notes how neither ADA nor JDRF currently fund Dr. Faustman's work, but they'll be monitoring the progress.

"(We) want every researcher in our field to be successful," the statement concludes. "Both organizations employ rigorous, peer-review processes to make evidence-based funding decisions, and we will continue to focus our resources on projects that we believe give us the best opportunity to create a world without T1D -- for ourselves and our loved ones -- as fast as we can."

JDRF Chief Mission Officer Dr. Aaron Kowalski tells us that while the two diabetes organization's have issued joint statements in the past with FDA on other scientific topics, this particular one related to Dr. Faustman is unique.

"We felt it was particularly necessary to be clear that the standard of care is not changing due to this report," he said, noting that clinicians were being contacted by families wanting the vaccination and mainstream news coverage of this certainly played a part in the D-Community interest and how the orgs decided to respond.

The ADA's Chief Scientic and Medical Officer Dr. William Cefalu echoed those sentiments, reiterating that there were too few patients included to make any determination about the benefits of this BCG therapy.

"This is a case where both organizations agreed on the limitations and concerns of the study and its findings, and we were aligned on making sure it was put into context," he told DiabetesMine:  

Cefalu says Dr. Faustman was allowed to present at ADA, as it wasn't immediately clear whether her pre-conference publication and late-breaking poster results shown at the SciSessions were in violation of the ADA's embargo policy. This conference is specifically about presenting the newest findings, and the embargo policy is meant to ensure no researcher "steals the thunder" before all the newest research is presented there. That's a standard for these types of medical, research-driven conferences.

"We are reviewing the timing and everything in detail," Cefalu says, noting that much of the ADA leadership and office staff is still traveling back from the conference at this time. "The issue was the paper was released so close to the presentation, and if that paper included the same information in the abstract, that's basically the definition of breaking an embargo."

 

Faustman's Response

Faustman says her team disagrees with the points in the joint statement, and also notes that they shared their media plan with the ADA in advance of the conference.

"I am not sure if (the joint statement) clarified anything for the millions of people who want progress toward a safe and viable intervention for type 1," Faustman told us. "We are very sensitive to comments that we are promising too much and have tried to be careful in how we communicate."

Regarding the detailed criticisms of her study, she added:

"Their specific comments on patient size and statistical significance are not supported by the P values. The scientific community uses P values specifically to avoid this type of conversation and there is zero data to suggest that natural variations could account for these changes.

"The other questions related to standard of care and insulin use are what we hope to answer in the Phase II trial, which is fully enrolled and underway. We will continue to try and engage with the JDRF, ADA or anyone interested helping us understand the potential of BCG. There is a lot of work left to do and we could use the support."

She noted that people interested in being part of her clinical trials can contact the trial coordinators at diabetestrial@partners.org.

"As we move forward, please reach out and let us know what you think (good and bad), but we ask everyone to be as civil as possible on all sides," Faustman added. "Our emotions are high because this condition is so hard for patients and the ones they love. Let’s stay together on this and see what we can do -- together!"

 

Hope vs. Hype

Faustman can be a polarizing personality, as we noted while walking the ADA convention center and poster hall talking to other researchers; you could easily sense the tension whenever her name was mentioned.

Some took the "cautious optimism" approach while others cringed and held up their hands to wave off the topic. We also heard more than once the view that she's peddling false hope for a cure.

Whatever your POV here, Dr. Faustman certainly stands as one of the most vivid examples of the "Hope v. Hype" phenom in diabetes research and how emotional it can get -- while the real-world impact of her research remains TBD.