[Ip-health] Drug Companies and Doctors Battle Over the Future of Fecal Transplants

Claire Cassedy claire.cassedy at keionline.org
Mon Mar 4 06:54:44 PST 2019


https://www.nytimes.com/2019/03/03/health/fecal-transplants-fda-microbiome.html

Drug Companies and Doctors Battle Over the Future of Fecal Transplants

As pharmaceutical companies seek to profit from the curative wonders of
human feces, doctors worry about new regulations, higher prices and
patients attempting DIY cures.

By Andrew Jacobs
March 3, 2019

CAMBRIDGE, Mass. — There’s a new war raging in health care, with hundreds
of millions of dollars at stake and thousands of lives in the balance. The
battle, pitting drug companies against doctors and patient advocates, is
being fought over the unlikeliest of substances: human excrement.

The clash is over the future of fecal microbiota transplants, or F.M.T., a
revolutionary treatment that has proved remarkably effective in treating
Clostridioides difficile, a debilitating bacterial infection that strikes
500,000 Americans a year and kills 30,000.

The therapy transfers fecal matter from healthy donors into the bowels of
ailing patients, restoring the beneficial works of the community of gut
microbes that have been decimated by antibiotics. Scientists see potential
for using these organisms to treat diseases from diabetes to cancer.

At the heart of the controversy is a question of classification: Are the
fecal microbiota that cure C. diff a drug, or are they more akin to organs,
tissues and blood products that are transferred from the healthy to treat
the sick? The answer will determine how the Food and Drug Administration
regulates the procedure, how much it costs and who gets to profit.

In 2013, the F.D.A. announced a draft decision to regulate the therapy as a
new drug but said it would continue to study the matter before reaching a
final decision — which is expected to happen soon. Critics say that
approach is based on outdated science and could lead to increased costs for
patients, most of whom currently rely on a nonprofit stool bank in
Cambridge. At stake, some researchers says, is the future of pioneering
therapies that harness the human microbiome — the trillions of organisms
that colonize the body and are increasingly seen as critical for healthy
brain development and immune function.

“People have good reason to worry because for many patients, fecal
transplants are a matter of life and death,” said Catherine Duff, founder
of the Fecal Transplant Foundation, a patients group. “The concern is that
corporate greed will get in the way of patient access.”

As the F.D.A. nears a final decision, both sides are ramping up the
pressure. More than 40 prominent gastroenterologists and infectious disease
doctors recently wrote to the agency, urging it to rethink its approach.

Dr. Alexander Khoruts, a gastroenterologist at the University of Minnesota,
said he feared the F.D.A. was favoring the interests of what he calls the
“poop drug cartel,” a group of companies seeking approval for new ways to
deliver the active ingredients in transplanted feces. Three of the
companies, Rebiotix, Seres Therapeutics and Vedanta Biosciences, have
raised tens of millions of dollars from investors and they recently formed
an association to advance their interests with the F.D.A.

“An obscene amount of money is being thrown around by companies trying to
profit off of what nature made,” said Dr. Khoruts. “I don’t think there are
clear villains here, but I worry that the regulators are not caught up on
the latest science and that the interests of investors may be exceeding
those of patients.”

Pharmaceutical executives and some doctors argue that the drug model will
help ensure the efficacy and long-term safety of a therapy whose mechanics
remain poorly understood.

“The first principle of medicine is do no harm, and at the moment we don’t
have a long-term track record of F.M.T.’s adverse effects,” said Dr. Sahil
Khanna, an associate professor of gastroenterology at the Mayo Clinic who
has conducted industry-funded clinical trials on fecal transplants. “We
also need to move away from transferring poo from one person to another.”

Experts in the field of bioethics and many doctors are pressing the F.D.A.
to come up with a new regulatory category that reflects the groundbreaking
nature of microbiota therapies.

Much like the fight over prescription drug prices, the “poop wars,” as one
doctor described it, mirrors long-running tensions in American health care
between pharmaceutical companies and patients.

Human feces, it turns out, are a potential gold mine, for both medical
researchers and drug makers.

According to the analytical firm GlobalData, the market for drug-based
treatments for C. diff is expected to reach $1.7 billion by 2026, up from
$630 million in 2016. The growth is tied to soaring rates of C. diff, which
parallel the overuse of antibiotics, leaving patients more vulnerable to
the infection.

Inspired by the success of fecal transplants for C. diff, scientists are
racing to develop similar treatments for an array of ailments and
disorders, among them obesity, autism, ulcerative colitis, and Alzheimer’s
and Parkinson’s diseases.

Investors, too, have taken note, and they are pouring tens of millions of
dollars into start-ups chasing the next microbiota breakthrough.

“The whole field is screaming forward faster than anyone could have
imagined,” said Lee A. Jones, chief executive of Rebiotix, which is testing
two products to treat C. diff. “The microbiome has the potential to change
the way we look at and treat disease.”

Such exuberance is a far cry from what researchers experienced when they
first tried to sell the curative power of human feces.

Mark Smith, a microbiologist at M.I.T., was halfway through his pitch with
a group of pharmaceutical executives when one of them interrupted to ask if
the meeting was a prank. “I can’t believe you wasted my time with this
crazy idea,” the man said, Dr. Smith later recalled.

That was 2012. Later that year he helped found OpenBiome, the nonprofit
stool bank that now supplies most of the fecal matter for transplants in
the United States. Three years ago, he started his own drug company, Finch
Therapeutics, which has raised $77 million.

Over the past decade, tens of thousands of Americans with C. diff have been
cured through fecal transplants, often with a single dose that can bring
patients back from the brink of death. The treatment has more than an 80
percent success rate, according to several studies, and many patients feel
better within hours of receiving the procedure, which is usually
administered through colonoscopy or capsules containing desiccated fecal
matter.

The F.D.A. has not formally approved the therapy but it has suspended
enforcement of its rules for patients who have failed on antibiotics while
it figures out the best way to regulate a regimen that, until recently, was
sometimes performed at home by desperate patients using an enema, saline
and a relative’s stool. Ms. Duff, the head of the C. diff patients group,
credits her own recovery from the disease to a homemade concoction her
husband created with his own stool in the kitchen blender.

The F.D.A. declined to comment for this article. Until the agency finalizes
its decision, many insurance companies will not cover the therapy.

Treating fecal transplants like a new drug requires pharmaceutical
companies to submit proposed products to an exhaustive investigative
process to assess their efficacy and safety, which can cost millions of
dollars.

Critics fear that designation would allow a drug company to gain the
exclusive right to sell a fecal transplant treatment for up to 12 years, a
move they say would stymie innovation.

Some also worry that patients unable to afford a company’s proprietary
therapy could turn to home remedies, putting them at risk for pathogens in
unscreened stool.

For now, most of the material used in fecal transplants comes from
OpenBiome, the public stool bank in Cambridge that embraces its mission
with both humor and gravitas. Giant poop emojis decorate its offices,
conference rooms are named after sections of the intestinal tract and
employee birthday cakes invariably come in one flavor: chocolate.

The organization produces 900 to 1,000 monthly treatments, most of them
bottled liquids that are packed in dry ice and sent overnight to clinics
across the country. Any unpleasant odors are confined to an airtight
production facility, where employees in white hazmat suits gingerly handle
clear plastic bags filled with a mud-colored slurry.

The material comes from donors who earn $40 a pop and must pass intensive
screenings and regular medical checkups. “It’s harder to become a stool
donor than it is to get into M.I.T.,” said Carolyn Edelstein, who runs the
organization.

In 2012, Ms. Edelstein created OpenBiome with Dr. Smith, now her fiancé,
after her cousin contracted recurrent C. diff and, facing a six-month wait
for the procedure, did it at home with a roommate’s stool.

A few months later they started OpenBiome with seed money from a foundation
and sent out six treatments that first year. “It’s been a wild ride,” Ms.
Edelstein said as she showed off a room full of mammoth freezers that hold
thousands of screened stool samples.

But OpenBiome and other stool banks are facing an uncertain future. Drug
companies, which have been struggling to funnel patients into the  clinical
studies that are required for F.D.A. approval, would like federal officials
to restrict the stool bank’s ability to distribute fecal matter in the hope
that more patients will enroll in their trials.

The F.D.A. has ramped up oversight of OpenBiome’s production, leading to
more rigorous testing and higher prices, which will double to $1,600 this
month.
Stephen Shaw of Providence, R.I., was successfully cured of C. diff with a
fecal transplant.

Patient advocates expect those prices to jump exponentially should the
F.D.A. grant market exclusivity to one of the companies that are in the
final stages of testing alternatives to raw stool transplants.

“It is very frustrating to see hyperregulation again ruining a good thing
in health care,” said Dr. Colleen Kelly, a gastroenterologist at the Brown
University medical school.

Her patients share her worry. Stephen Shaw, 66, a retired truck driver,
spent much of last year tethered to a toilet as he battled C. diff. A
diabetic, Mr. Shaw acquired the intestinal affliction the way many people
do: during hospitalization for a series of infections treated with repeated
rounds of antibiotics.

“I couldn’t go anywhere for fear I was going to blast out,” he said,
recalling the many times he soiled himself. “My life was destroyed.”

In late December, Dr. Kelly administered a fecal transplant via
colonoscopy, and within hours, Mr. Shaw started feeling better. By
Christmas his bowel movements had returned to normal.

“I never imagined the solution to my nightmare could be so simple,” he
said. “I just hope Big Pharma doesn’t make it unaffordable for the people
like me.”


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