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Thursday, July 11, 2019

Israeli medical aesthetics company InMode files for a $75 million US IPO

InMode Limited, which develops and markets minimally-invasive medical aesthetic products, filed on Thursday with the SEC to raise up to $75 million in an initial public offering.
The Yokneam, Israel-based company was founded in 2008 and booked $110 million in sales for the 12 months ended March 31, 2019. It plans to list on the Nasdaq under the symbol INMD. Barclays and UBS Investment Bank are the joint bookrunners on the deal. No pricing terms were disclosed.

Biophytis boosts size of U.S. IPO

In a quick amendment to its registration filing from earlier this week, France’s Biophytis (BPTS) says it will now offer 15M shares (including 10M ordinary shares in the form of American Depositary Shares) through H.C. Wainwright.
That’s up from 13.1M ordinary shares, 8.75M of those in the form of ADS.
It still expects to price the offering at $7-$9/ADS (about €0.62-€0.80 per ordinary share). Yesterday, the last reported sale price of ordinary shares in Paris as €0.80, currently corresponding to a price of $8.98 per ADS.

New Insights into the Vagus Nerve Could Change the Way Diabetes is Treated

A new discovery at the Feinstein Institutes for Medical Research could have implications in the way diabetes is treated in the future.
A research team helmed by Theodoros Zanos, head of the Neural & Data Science Lab, discovered how the vagus nerve relays signals from the periphery to the brain to help regulate glucose. Previous research has revealed that the vagus nerve, which connects to numerous organs throughout the body and communicates changes in the body to the brainstem, plays a role in regulating metabolism. However, how the vagus nerve did this was not understood. Zanos and his research team set out to identify the specific signals relayed from the periphery to the brain that responded to changes in glucose levels. And that was just what they did. Now, this discovery could have implications in revealing a new way to measure blood glucose levels in people. Zanos’ findings were published in the Springer Nature journal, Bioelectronic Medicine.

In a statement, Zanos said they believed that listening to and stimulating the vagus nerve would open new possibilities to the diagnosis and management of various diseases.
“The vagus nerve is one of the major information conduits of the body with an average of 100,000 nerve fibers, making this code difficult to pick up and decipher, so we have a lot to learn,” Zanos said. “We’re excited to demonstrate in this most recent study that the vagus nerve of a mouse transports important signals from the periphery to the central nervous system related to glucose homeostasis – this discovery gets us closer to new technologies that will have the potential of helping many patients living with various metabolic diseases.”
In addition to serving as a highway for sensory information from organs to the brain, the vagus nerve also plays a role in regulating the heart rate and keeping the gastrointestinal tract in working order.
Feinstein Institutes President and Chief Executive Officer Kevin J. Tracey was a co-author of the paper, “Identification of hypoglycemia-specific neural signals by decoding murine vagus nerve activity.” The discovery made by Zanos and his team, Tracey said, “gives us new understanding of the body’s neural signaling and offers hope for diabetes management.”

This was not the first discovery that Zanos and his team have made with a potential to change the way a disease is treated. Last year, Zanos and team were the first to decode specific signals the nervous system uses to communicate immune status and inflammation to the brain. The identification of these neural signals and their role in the body’s health was a step forward in bioelectronic medicine, the Institute said. It provides provided insight into diagnostic and therapeutic targets, and device development. Bioelectronic medicine is a new approach to treating and diagnosing disease and injury that has sprung from the Feinstein Institutes’ labs. It uses new technology to read and modulate the electrical activity within the body’s nervous system, opening new doors to real-time diagnostics and treatment options for patients, the Feinstein Institute explained.

The Wild West of Anti-Aging Medicine

In a remote fishing lodge in Soldotna, Alaska—a town of just over 4000 people along 2 million pristine acres of protected wilderness—Dr Robert Ledda leads a specialized medical practice designed to help his patients manage or even optimize aging. People travel here with a wish list that seems endless: more energy, less stress, a sharper brain, a stronger libido, a healthier heart, more resilient muscles and bones, a better immune system, a more youthful appearance.
The problem with “mainstream medicine,” says Ledda, is that it’s disease-oriented and reactive, not preventive: That is, nurses and physicians see patients when they’re sick, not sooner.
“They don’t have the time,” says Ledda, a partner with Cenegenics Alaska, a branch of Cenegenics Medical Institute. Most doctors can’t spend 8 hours the first time they see a patient, as he does, evaluating activity levels, family history, stress, and eating habits. “They know that the vast majority of people are not going to change the way they live, so their tool bag is strictly disease-model and medication-based.”
In its marketing materials online and on social media, Cenegenics claims its elite, pricey program—or “healthy aging plan”—will “reverse the declines of aging and protect your future health.” Cenegenics clinics worldwide offer the same promise, from Boston to Columbus, Ohio, to Karnataka, India.
Physicians who specialize in so-called anti-aging medicine have long operated on the outskirts of the medical profession, and they draw their share of criticism, particularly for prescribing hormone therapy.
On a website called HGH Watch, longevity expert Thomas Perls, MD, MPH, characterizes the prescribing of human growth hormone (HGH) for anti-aging as “quackery and hucksterism.” Perls, a professor of medicine at the Boston University School of Medicine, also writes that hormone replacement therapy“and the drugs used to treat their side effects end up being hormonal toxic soups that can cause great medical and financial harm that far outweighs any long-term benefit.”
But as physicians brace for growing numbers of aging patients who hope to live longer and have a better quality of life in their older years with less disease, some treatments previously waved off as too emerging, expensive, or even vain are slowly becoming more accepted. The idea is that aging is inevitable, yes, but it’s also treatable—and even somewhat preventable.
“There’s way more scientists who are coming around [and] agree with our approach of primary prevention,” says Ledda, whose certification in age management medicine is a credential that is not recognized by mainstream medicine.
Still, the ranks of doctors who practice anti-aging and age management medicine are growing. The American Academy of Anti-Aging Medicine—which states its mission is to support research and technology that will “detect, treat, and prevent diseases associated with aging,” as well as treatments “designed to prolong the human life span” and “optimize the human aging process”—now has over 26,000 members. Of these, 85% are physicians and 12% are researchers, scientists, and “health practitioners.” (The remaining 3% is a mix of people, including members of the public.)

‘Specializing’ Without a Specialty

The question is, are these interventions that claim to combat the effects of aging based in science? Critics argue that the anecdotes and testimonials don’t pass the rigorous standards set by evidence-based medicine. Without clinical trials, the purported effects aren’t measurable or proven by legitimate science.
“Most of traditional medicine has taken a negative stance, I would say, against these [anti-aging interventions] because again, does it work? And is it safe? We can’t answer those questions,” says Dr Cynthia Stuenkel, a clinical professor of medicine at the University of California, San Diego, who published a warning about compounded bioidentical hormone therapy in JAMA Internal Medicine in 2017. Stuenkel also chaired the Endocrine Society’s treatment guidelines for menopause in November 2015.
The American Board of Medical Specialties (ABMS) does not certify a specialty or subspecialty for anti-aging. “[Our] process to establish a new specialty or subspecialty is rigorous and thoughtful,” ABMS said in a statement. “It involves input from internal and external stakeholders, public comment, committee review, and is ultimately an ABMS Board decision.” To qualify as a specialty, the area of medicine must focus on a “distinct and definable” group of patients, a “definable type of care need,” a “stand-alone” set of medical knowledge, or “unique care principles,” as well as “clearly demonstrating its value in improving access, quality, and coordination of care.”
“I’m not worried about them infiltrating legitimate medicine,” says S. Jay Olshansky, PhD, a gerontology professor at the University of Illinois at Chicago School of Public Health.
“The fact that there is no medical specialty called ‘anti-aging medicine’ is all that you need to know,” Olshansky says. “This has been the case from day one. Nothing’s changed.” On the other hand, he applauds the efforts of “anti-aging” doctors who encourage their patients to adopt a healthier lifestyle.
“Does that modulate some of the effects of aging? Yes, of course,” he says. “If you exercise, eat right, and lose weight, chances are you’re going to feel better, and you’ll probably live healthier for a longer time period. So if that’s what you’re doing, and you’re calling yourself an anti-aging doctor, then there’s a legitimate element to what you’re doing.”

Focusing on Prevention

Robert Ledda, MD
With the exception of one crucial component of his practice—prescribing hormones—Ledda’s strategy for his patients is largely preventive, beginning with a $2500 evaluation day that generates a baseline report. Then, patients begin a program of consistent exercise, a low-glycemic diet, hormone manipulation, and a handful of daily supplements. The first annual visit costs $2495, and subsequent check-ups are $1995. The monthly program fee in the first year is $350, plus the costs of the supplements, hormones, and lab work.
Ledda shares the story of his aunt, Pam, who hadn’t seen a doctor in 3 years when she first visited his practice. The “before” photo on his clinic’s Facebook page shows a 60-year-old woman with a sweet smile and a mix of gray and golden brown hair. The scale told a different story: At 209 pounds, she was morbidly obese.
“You go to a regular disease-model doctor, you’re going out the door on a blood pressure medicine, a cholesterol medicine, and a diabetes medicine,” Ledda says he remembers thinking after reviewing her first set of lab work. “The disease-model recipe was to start insulin. So we’re talking real disease here.”
Gradually, Pam began to feel motivated to change. She started attending Ledda’s lecture series, and she also worked with Ledda’s low-glycemic (“paleo”) chef for a week to learn how to cook.
One motivator that works for many patients is fear, Ledda says. “I can create some fear that’s a little more concrete than, Someday I may have problems, but right now I just want to eat the cake. The challenge with every patient is really getting a hold of their psyche to the point where they realize they just can’t keep doing that.”
That fear transformed his aunt’s life, he says: She changed what she ate and began exercising in a CrossFit gym 3 days per week, and she lost a significant amount of weight. Now, she is more fit and feels better. “She’s had improvements subjectively in every domain you could think of, and all of her numbers are great. Her systemic inflammation went away,” Ledda says. In her “after” photo posted on Facebook, she is far thinner, in workout gear: a beige hoodie, sneakers, and tight black leggings. She’s standing with a pal outside a big wall emblazoned with graffiti, with a wide, confident smile.
Though Ledda says he put her on some “conventional meds” for high cholesterol and diabetes after her initial visit, he has now “taken her off almost everything”; now, “she has no metabolic disease at all,” no diabetes, and her “cholesterol panel is immaculate on no medicines.”
At her first visit, Pam’s total cholesterol was 280 mg/dL; her bad cholesterol was 200, and her good cholesterol was quite low, in the 30s. Ledda attributes the transformation to a handful of things working together: diet, supplements, lifestyle changes, and weight loss. Now, she takes 500 mg of metformin daily, as well as a number of nutritional supplements. She’s also on hormone replacement therapy.

Changing the Hormonal ‘Soup’

Perhaps the most controversial element of the Cenegenics program is its focus on manipulating hormones in the aging body.
The regimen for women can include potentially dangerous bioidentical compounds, whereas men may be offered testosterone HGH, which has not approved by the US Food and Drug Administration (FDA) for anti-aging purposes. HGH has only been cleared for use in patients with HIV and for a rare condition in children called “adult growth hormone deficiency,” a diagnosis that has proved to be popular among anti-aging doctors.
Women who experience early or surgical menopause typically experience poorer cardiovascular, bone-density, and cognitive outcomes, as well as an increased risk of developing diabetes, Ledda says, which is why they are advised to undergo hormone replacement therapy. It can help most women who go through menopause.
“Why not continue them longer to continue to get those obvious benefits that science suggests are there?” he asks.
The Endocrine Society has come out against the use of HGH except in patients with clearly defined evidence of a growth hormone deficiency, Stuenkel says—for example, if they had a pituitary tumor or hypothalamic dysfunction. Another hormone to watch out for, she adds, is dehydroepiandrosterone (DHEA), an adrenal androgen male hormone. It’s controversial because of the lack of good evidence supporting its use.

New Use for an Old Drug?

One potentially promising drug that has already been tested in millions of patients is metformin, a diabetes medication that some of Ledda’s patients—including his aunt Pam—take to manage insulin resistance. “Ultimately, over many years of studying with tens of thousands of patients, we will learn if those people are healthier for longer—and then, we’ll have our first evidence that we’re on the right path,” says David Sinclair, a longevity researcher at Harvard who serves as an advisor for several biotech projects.
Patients who have taken the drug have less cancer, less heart disease, and less frailty than the average population, an effect that is “firmly based in science,” Sinclair says. “But because aging isn’t considered a disease, and you’re not diabetic until you actually have high blood sugar, you can’t easily get metformin as a preventive measure,” he adds.
The next step, Sinclair says, is securing funding to launch a massive study to test its safety and efficacy: the Targeting Aging with Metformin (TAME) trial, led by Albert Einstein College of Medicine’s Dr Nir Barzilai, who previously conducted the Metformin in Longevity (MILES) study. The National Institutes of Health rejected its grant proposal last fall, but if the trial gets off the ground, researchers will follow 3000 patients who are between 65 and 79 years old. The trial has support from the American Federation for Aging Research, and researchers hope it will show the FDA that aging can be slowed, and therefore can be treated as a medical condition, Sinclair says.
“Metformin could be the first drug that would be given to people in their 50s and 60s before they get sick, whereas now we wait until it’s too late.”
In the meantime, experts such as gerontology professor Olshansky remain skeptical about doctors promising to turn back the clock with “anti-aging” treatments that have not been proven effective.
“Mainstream medicine has not accepted this premise,” he says.

Doubled Risk of Death After Minimally Invasive Surgery for Cervical Cancer

Another blow has been dealt for minimally invasive surgery (MIS) in patients with cervical cancer — this time by Canadian researchers.
They report a population cohort study, which they say better reflects ‘the real world impact’ of such surgery. Their review of nearly 1000 patients with early stage cervical cancer found a twofold higher risk of death and cancer recurrence in those who underwent minimally invasive surgery (MIS) compared with those who had an open radical hysterectomy. The finding held even after controlling for surgeon volume.
The study was published online July 6 in the American Journal of Obstetrics and Gynecology.
The new findings echo those reported last year from two studies published in the New England Journal of Medicine.
“Rather surprisingly, and some would say shockingly, both studies showed a significant inferior survival associated with the use of the minimally invasive procedures,” Maurie Markman, MD, from Cancer Treatment Centers of America in Philadelphia, commented at the time.
The data from the two studies “have shown rather convincingly — and I would say definitively — that these minimally invasive procedures should not be performed, except under perhaps extraordinary circumstances where there is a serious risk for the patient associated with the standard approach,” he said.
Now, with the newly published Canadian findings, Markman is even more convinced that there are real dangers in using a minimally invasive approach in the treatment of cervical cancer.
“These disturbing data…again emphasize the critical need for well-designed and well-controlled clinical trials before a ‘novel surgical approach’ should be accepted as standard-of-care in cancer management,” he told Medscape Medical News in an email.
Monica Bertagnolli, MD, chief of surgical oncology at the Dana-Farber Cancer Institute in Boston, Massachusetts, and president of the American Society of Clinical Oncology, told Medscape Medical News recently that the results showing inferior oncologic outcomes after minimally invasive surgery in cervical cancer are “very very sobering.”
In general, more rigorous studies of minimally invasive cancer surgery are needed. What is most important, said Bertagnolli emphatically, is cancer outcomes — and not short-term benefits.
The Food and Drug Administration (FDA) has also expressed concern. In February, the agency issued a ‘caution’ about the use of robotically-assisted surgical devices in women’s health, and this included minimally invasive surgery for cervical and breast cancer.
The agency urged caution about any such use, noting that robotic devices are approved for use in prostate cancer but not in most cancers.

Advantages of Minimally Invasive Approach?

Arguments in favor of the minimally invasive approach include a shorter postoperative hospital stay, fewer complications, and smaller incisions, resulting in quicker recovery time and improved patient satisfaction compared with open surgery.
However, as one Medscape reader working in Ob/Gyn and women’s health commented: “I would suggest that the protocol of minimally invasive radical hysterectomy has benefited the bottom line of hospitals and insurance providers.
“I challenge all gynecologists to search for any protocol change that financially benefits hospitals and insurance companies that has truly benefited the patient,” the reader wrote in the comment section of the Markman article.
Another clinician in women’s health commented in agreement: “Well, finally, someone who has the good sense to state the obvious. Minimally invasive surgery for cancer has as its main beneficiaries the health insurance industry (reduced length of stay) and the companies that manufacture all that wonderfully expensive equipment used for the procedure, not the patient whose survival time is not a factor in revenue to the medical system.”

New Data From Canada

The new data from Canada come from a population-based retrospective cohort study of patients with cervical cancer who underwent a primary radical hysterectomy by a gynecologic oncologist from 2006–2017 in Ontario.
The team identified 958 women,958 women (mean age, 45.9 years) with predominantly stage 1B cervical cancer who underwent radical hysterectomy within 9 months of their diagnosis.
Open radical hysterectomy was done in half of the cohort; in the other half, 90% of the minimally invasive procedures were performed laparoscopically.
Patients undergoing minimally invasive radical hysterectomy were less likely to have high-risk features and fewer comorbidities than women who underwent open radical hysterectomy, the researchers note.
At a median follow-up of 6 years, “minimally invasive radical hysterectomy was associated with a two-fold higher rate of all-cause death and recurrence compared to open radical hysterectomy in patients with stage 1B disease, but not 1A or 2+ disease,” Maria Cusimano, MD, from the University of Toronto, and colleagues report.
This relationship held even after adjusting for patient factors as well as surgeon volume, they add.
The researchers note that, in contrast to the previously reported studies, “this population-based patient-level analysis reflects the real-world impact of minimally invasive radical hysterectomy, as performed by unselected surgeons on unselected early-stage cervical cancer patients,” the investigators write.
“Open hysterectomy should be the recommended approach in this population,” they conclude.

MIS Now Used in at Least Half of Cases

The new Canadian findings will undoubtedly fuel the argument that minimally invasive surgery is not as favorable as open radical hysterectomy in early cervical cancer — and this at a time when the proportion of early cervical cancer being treated with less invasive surgery is exploding.
For example, minimally invasive procedures accounted for more than half of all radical hysterectomies done for the treatment of cervical cancer in 2013, according to the authors of the National Cancer Database analysis that was published in the New England Journal of Medicine last year.
In the new Canadian cohort study, the proportion of cervical cancers treated using minimally invasive techniques — at least in the province of Ontario — climbed from 4.8% of all hysterectomies in 2006 to 65% in 2017.

Experts Caution Against It

Commenting on the National Cancer Database results last year in an accompanying NEJM editorial, Amanda Fader, MD, Johns Hopkins School of Medicine, Baltimore, Maryland suggested that select patient subgroups may still benefit from the less invasive approach. One example would be patients with tumors measuring less than 2 cm prior to surgery — for these types of patients, the outcomes were not worse with MIS in either of the two studies.
However, until it’s clear that the less invasive approach is equivalent to open hysterectomy in specific subgroups of patients, Fader urged surgeons to proceed with caution and to counsel their patients about these findings so that women are aware that there is a higher risk of recurrence with minimally invasive surgery than with open radical hysterectomy.
However, Markman in his Medscape commentary went a step further, and said that, at least from his perspective, minimally invasive radical hysterectomy should no longer be considered a standard-of-care for the treatment of early-stage cervical cancer.
In another commentary about the two studies, published earlier this year in the Journal of the National Comprehensive Cancer Network, Kathryn Pennington, MD, from the University of Washington Medicine in Seattle, and colleagues say that open radical hysterectomy and not a less invasive approach should now be considered standard-of-care for stage 1A2-1B1 cervical cancer.
Patients who still want to undergo less invasive surgery should be “guided appropriately”, they suggest, in order to make a more informed decision about which approach they would prefer their surgeon to take.
The Canadian authors have disclosed no relevant financial relationships. Markman has received grants from Genentech, AstraZeneca, Celgene, Clovis, and Amgen. Fader has received personal fees from Ethicon outside the submitted work. Pennington and Bertagnolli have disclosed no relevant financial relationships.
Am J Obstet Gynecol. Published online July 6, 2019. Full text

California to Repay Loans of Docs Who Take Medicaid Patients

California has launched a program that will repay young doctors’ medical school loans if they agree to carry a caseload 30% of which consists of patients on Medi-Cal, the state’s Medicaid program.
This year, the CalHealthCares program will repay student loans totaling $58.6 million for 247 physicians in 40 specialties, including pediatricians, psychiatrists, and obstetrician/gynecologists, according to a news release from the California Department of Health Care Services (DHCS), which administers Medi-Cal.
These physicians were selected from more than 1300 who applied to the program.
The state will pay off loans of up to $300,000 over a 5-year period. That’s the same amount of time for which the recipient doctors have committed to caring for underserved patients.
This is the first of five rounds of awards to doctors and dentists from the CalHealthCare program. The DHCS will start accepting applications for the next round in January.
The money for the loan repayment is coming from an increase in the state tobacco tax that took effect in 2017, according to the Sacramento Bee. The following year, the legislature established the loan repayment program and appropriated $220 million for it. Gov. Gavin Newsom added $120 million to CalHealthCares in his recently approved 2019–2020 budget.

Physician Shortage

California is not doing this just to help physicians. It desperately needs more doctors to serve the growing Medi-Cal population, which includes 1 in 3 Californians. The expansion of Medi-Cal under the Affordable Care Act added about 4 million people to the rolls, according to a news story on the website of KQED, a public radio station in northern California.
Medi-Cal also covers about 200,000 undocumented children. The recently enacted state budget includes funding for Medi-Cal coverage of nearly 100,000 undocumented adults.
Many Medi-Cal beneficiaries have difficulty obtaining access to care. One reason for this is that there aren’t enough physicians in the poverty-stricken areas where Medi-Cal beneficiaries live. In addition, Medi-Cal pays providers very little, even by Medicaid standards. The program reimburses doctors at 52% of Medicare rates; nationwide, the average Medicaid payment is 72% of Medicare rates, according to the California Health Care Foundation (CHCF).
Unsurprisingly, just 60% of California doctors accept new Medi-Cal patients; in contrast, 77% take new Medicare patients, and 85% take new patients covered by commercial insurance. In 2015, a study conducted by the CHCF found that 34% of primary care doctors had no Medi-Cal patients. Just 28% of doctors had as many Medi-Cal patients as the physicians whose loans are being repaid must have.
The large number of applications to CalHealthCares can be attributed to the heavy loan burdens that young doctors carry. Nearly half of US medical school graduates now leave residency with loans of $200,000 or more, according to a survey by Merritt Hawkins, a physician recruiting firm.
Other national and state loan repayment programs also encourage doctors to work in underserved areas. For example, the National Health Service Corps Loan Repayment Program offers up to $50,000 in repayments for primary care physicians who work for at least 2 years in a health professional shortage area. The Association of American Medical Colleges offers a database of state and federal loan repayment programs.
Considering that there are more than 60,000 practicing physicians in California, how much of a difference would it make to inject 247 physicians temporarily into areas with large Medicaid populations? More than you might think, Janice Coffman, PhD, MPP, a professor at the University of California, San Francisco, told the Sacramento Bee. The 5 years required by CalHealthCares, she said, is enough time for young doctors to make friends and put down roots in the community.

Lawmakers seek scientific review of plan to tightly regulate all fentanyl copycats

Lawmakers on the U.S. Senate Judiciary Committee have urged the Trump administration to conduct a scientific review of a Justice Department-backed bill to classify all illicit chemical knockoffs of the potent painkiller fentanyl in the same legal category as heroin.
The sweeping legislation may “deter valid, critical medical research aimed at responses to the opioid crisis,” the senators said in a July 10 letter to Department of Health and Human Services (HHS) Secretary Alex Azar seen by Reuters on Thursday.
Lawmakers and health officials have said fentanyl, which is about 100 times more potent than morphine, has fueled the opioid overdose epidemic.
As prescribed by physicians, fentanyl is classified as a Schedule II drug, meaning it is highly addictive but has a medicinal purpose, typically to treat intense cancer pain.
But chemists primarily in China have created numerous slightly altered versions of the drug, known as “analogues,” that have hit the U.S. streets.
If the draft bill is passed by Congress, it would place all illicit fentanyl analogues in Schedule 1, along with heroin, would means that they are addictive, have no medicinal purpose and are effectively banned.
The legislation is designed to help prosecutors keep pace with criminals who churn out chemically tweaked fentanyl analogues to evade strict Schedule I regulations.
But scientific experts, including some within HHS, contend that automatically placing all analogues into Schedule 1 could stifle research to combat the opioid crisis. They argue that Drug Enforcement Administration (DEA) regulations to win approval for such research are so onerous that they will deter many scientists from applying for needed waivers.

In their letter to Azar, senators said the administration had “not adequately consulted with public health agencies” about the impact of classifying all fentanyl analogues as Schedule I.
“We are concerned that the failure to engage necessary health experts vests far too much authority to a law enforcement agency,” they wrote, adding that it could also “deter valid, critical medical research.”
The letter was signed by Democratic Senators Richard Durbin, Sheldon Whitehouse, Amy Klobuchar, Christopher Coons, Mazie Hirono, Cory Booker and Kamala Harris, as well as Republican Senator Mike Lee.
A spokesperson for HHS confirmed receiving the letter and said all congressional inquiries are taken seriously.
The DEA did not have any immediate comment.
The letter came after Reuters this week reported about an ongoing interagency dispute between an office within HHS and the DEA over the proposed fentanyl analog legislation.
In a June 20 closed-door briefing with Senate Judiciary Committee staffers, an official from the National Institute on Drug Abuse warned that the bill as drafted could create regulatory hurdles that will make it too hard for scientists to research possible medical benefits of fentanyl analogues.
Such benefits could include antidotes to overdoses, or the creation of pain killers without addictive properties.
Normally, the DEA and the U.S. Food and Drug Administration review chemical compounds individually to assign each one a controlled substance classification, with the FDA determining if such “scheduling” decisions are scientifically valid.
The draft bill, introduced by Republican Senator Ron Johnson and Republican Representative Jim Sensenbrenner, would cut the FDA out of that process.