Enrollment ongoing at multiple sites in the US and Europe; site initiation in Asia expected in November 2022 -
- Enrollment on pace, with over 30% enrolled in the United States -
- Topline data for RECOVER evaluating brilaroxazine for schizophrenia expected in mid-2023 -
https://finance.yahoo.com/news/reviva-pharmaceuticals-announces-global-enrollment-120000187.html
#MyOzempicJourney has gone viral on TikTok. People are calling their doctor's offices requesting semaglutide (Ozempic) by name to get the same dramatic weight loss transformations they've seen online.
Sylvia Gonsahn-Bollie, MD
As an obesity expert who was an early adopter of the glucagon-like peptide 1 (GLP-1) agonists, the class of medication semaglutide belongs to, I have mixed feelings about its new popularity as well as other weight loss medications. However, I'll try to present a nonjudgmental view of the clinical considerations of weight loss medications. Specifically, I want to discuss the benefits and potential harms of using weight loss medications.
First, let's start with a bit of housekeeping on what we call these medications. Medications used to reduce weight or treat obesity are commonly called "weight loss medications." But the correct US Food and Drug Administration (FDA) term is "anti-obesity medications" or "AOMs."
The term "anti-obesity" can be offensive to some patients. So my preferred term is "metabolic medications," which emphasizes that "weight loss medications" do more than induce weight loss. Metabolic medications also improve metabolism and, for some medications, also improve cardiometabolic health. Therefore, in this piece, I'll use the terms "weight loss medications," "metabolic medications," and "anti-obesity medications" interchangeably.
Let's start with the benefits of metabolic medications.
Treat the root cause of hormonally driven weight gain. Obesity is a complex medical disease with health consequences beyond the scale. In the past 10 years, our understanding of the pathophysiology of obesity has increased significantly. Fitness, healthy food choices, and other lifestyle changes are foundational to weight loss and obesity treatment. But for many people, these lifestyle changes aren't enough to lose and sustain weight. The development of medications that affect the incretin pathway, like GLP-1 agonists, is groundbreaking. GLP-1 agonists mimic the body's natural satiation pathway, which helps improve hunger, decrease energy intake, and improve glycemic control. Moreover, these medications suppress the body's "weight regain" mechanisms.
Provide more tools for metabolic equity. Everyone is not playing on the same metabolic playing field. We know this from studies of twins which show a genetic predisposition to gain weight or develop obesity. Additionally, weight regulation is more complex than "calories in vs calories out." Over 70 weight gain triggers make some people prone to gaining weight. A common misconception is that taking a weight loss medication is cheating or giving the patient an "unfair" weight loss advantage. However, the opposite is true. In a person with insulin resistance, diabetes, or obesity, metabolic medications only level the metabolic playing field by addressing the underlying weight gain triggers that prevent weight loss.
Result in less blame for "failed" lifestyle changes. "I failed my diet." I can't tell you how often I've heard this phrase or said it myself. People unfairly experience blame and shame when they don't lose significant weight through lifestyle changes or regain the weight. However, data shows most people will lose only 2%-5% of their body weight with lifestyle changes alone. Studies show that up to 80% of weight will be regained within 5 years. These sparse numbers are due to more than willpower. As I mentioned, powerful neuroendocrine pathways signal your body to regain the lost weight. Taking metabolic medications suppresses these pathways.
However, in addition to the benefits, the recent popularity of weight loss medications like semaglutide does highlight some potential harms.
Weight bias. An obsession with thinness has been the standard of beauty in Western culture for over a century. As Dr Sabrina Strings highlights in her thought-provoking sociological book Fearing the Black Body, this preoccupation with thinness has both racist and sexist origins. Even the standard body mass index (BMI), the most commonly used tool for obesity screening, is biased. Prompting calls for body composition and other metabolic health indicators to be used for health assessment instead of the standard BMI, as I wrote in my previous Medscape column. The prevalence of weight bias in society and healthcare raises the question, "Are we using metabolic medications for thinness or health?" Obviously, as clinicians, our goal is health optimization. However, we must be careful not to let weight bias obscure our objective clinical assessment.
Furthermore, in the past decade, significant strides have increased the acceptance of body diversity and individualized healthy weight. However, people exploiting semaglutide and other medications off-label to become super-thin threatens the progress in body diversity acceptance. It also emphasizes the medications' weight loss properties, which can overshadow metabolic medications' life-saving benefits for people with a medical indication for taking semaglutide and other metabolic medications.
Health inequity. Newer GLP-1 agonists can markedly improve the health of people with diabetes or obesity. However, diverting metabolic medications to people for off-label or cosmetic use is causing medication shortages. Furthermore, the cost is prohibitive to people who need them most. The unjust access to newer anti-obesity medications worsens health inequity and health disparities.
Risky prescribing practices. The "street value" of an Ozempic prescription is $1200-$1500. The public views Ozempic as a safe drug, with "only stomach side effects." Scripts are given without essential prescreening and monitoring to decrease drug risks. However, it's easy to miss serious risks when selling prescriptions without screening and tracking. For example, GLP-1 agonists increase thyroid cancer risk in people with a specific family history. Again, it's easy to overlook this risk without taking a family history. Lastly, all medications have side effects. Although GLP-1 agonists like semaglutide have undergone extensive testing, there are still risks for new side effects. Therefore, people taking semaglutide and other metabolic medications need monitoring.
Unhealthy weight loss. One celebrity boasted about her "18% body fat" due to Ozempic. This body fat percentage is at the lower limit of normal. Fat is an essential body organ, especially for women, who need higher body fat levels than men. Anti-obesity medications are intended to reduce excess fat levels to improve metabolic health, not make people underweight. Furthermore, another undesired side effect of GLP-1 agonists is the loss of muscle mass. Using metabolic medications in the wrong population increases the risk for lowering body fat and muscle below healthy levels.
Weight regain. Whatever you do to lose weight, you've got to be able to do even more to maintain weight loss. Weight gain is your body's default mode. That's why weight regain is common. Unfortunately, studies also show weight regain with GLP-1 agonist cessation. Weight loss and obesity treatment require a comprehensive biopsychosocial approach to maintain weight loss and improve health. If people only take weight loss medications without other lifestyle changes, it's unlikely that the weight will stay off without the prescription.
As doctors and clinical prescribers, we can access the most innovative and effective weight loss and metabolic health improvement tools. Anti-obesity medications/metabolic medications are here to stay and will only improve as technology advances. Therefore, we must use our prescribing power to enhance people's lives for not only short-term weight loss, but also long-term health improvement. That starts with ensuring we prescribe appropriate medications to the right persons. When we give people "weight loss medications," we are also affecting their metabolic health.
Data, not societal trends, must guide our clinical judgment. The desire for people to alter their bodies to fit an ever-elusive beauty standard is as old as time. Last year, curvy was in. This year, thinness is back. That's why we clinicians must check our biases, so that we base our medical treatment on facts, not fads.
Sylvia Gonsahn-Bollie, MD, DipABOM, is an integrative obesity specialist who specializes in individualized solutions for emotional and biological overeating. Connect with her at www.embraceyouweightloss.com or on Instagram @embraceyoumd. Her bestselling book, Embrace You: Your Guide to Transforming Weight Loss Misconceptions Into Lifelong Wellness, is Healthline.com's Best Overall Weight Loss Book 2022 and one of Livestrong.com's picks for the 8 Best Weight-Loss Books to Read in 2022.
One expert's clinical experience suggests that Ellacor, a dermal microcoring device that became available in the United States in October 2022, is an effective treatment for facial wrinkles and tightening.
Dr Mathew Avram
"It's early yet, but I have treated dozens of patients with this device, and they have been happy with the results," Mathew M. Avram, MD, JD, said at the annual meeting of the American Society for Dermatologic Surgery. "This is a new technique that offers the ability to remove a significant amount of damaged, lax skin without concern for scarring," he said.
A brainchild of dermatologists and plastic surgeons at Massachusetts General Hospital, Boston, the first-in-class device is cleared by the Food and Drug Administration for the treatment of moderate and severe wrinkles in the mid and lower face in adults aged 22 years or older with Fitzpatrick skin types I-IV. It features a proprietary needle design that makes a series of high throughput microexcisions in epidermal and dermal tissue, with minimal downtime and without using thermal energy.
"It doesn't do anything equivalent to a facelift, but the concept is a facelift by thousands of micro-punch excisions," said Avram, director of laser, cosmetics, and dermatologic surgery at Massachusetts General Hospital. "Rather than pulling up the skin and lifting it and cutting the excess skin like we do with a facelift, we are creating thousands of smaller-scale tissue removals with immediate closures to do the same thing. The micro-cores are about the size of a 22-gauge needle and there is no scarring due to the small size of these tissue extractions."
The device features needle cartridges capable of excising up to 24,000 cores per treatment. According to data from Cytrellis, the manufacturer, the equivalent of about 2 inches of skin can be removed during the procedure, which typically takes fewer than 30 minutes to perform. "There is no heat whatsoever," Avram said. "In my experience, it especially helps with jawline definition, the lower medial cheek excess skin, and accordion lines in that area."
In a pivotal trial of the device, 51 patients with mid to lower face wrinkles (moderately deep or deep wrinkles with well-defined edges) were treated 2-3 times with 7%-8% skin removal and up to a 5-mm needle coring depth). The investigators found that 40% of study participants achieved an improvement of 2 grades on the Lemperle Wrinkle Severity Scale and that the rate of overall satisfaction (slightly, somewhat, and extremely satisfied) was 86%.
In addition, 90% showed improvement of treated sites on the Global Aesthetic Improvement Scale, and 70% were comfortable enough to go out in public or return to work 3 days after treatment. Common side effects that can occur immediately post treatment include redness, swelling, and pinpoint bleeding, which typically clear in a few days.
Avram, immediate past president of the ASDS, has posted videos to his Instagram feed that show him treating patients with the Ellacor device and he admits that the procedure looks painful. "There are all these tear emojis and people cursing me out," he said, referring to responses from his Instagram followers.
Proper local anesthesia prior to treatment is key. "I perform nerve blocks and infiltrate the skin," he said. "You have to cover the whole treatment area. If you don't, then it's going to hurt. The average pain score is 1.9 out of 10. The highest pain score I've gotten from a patient is a 3 out of 10."
Avram disclosed that he has received consulting fees from Allergan, Merz, Sciton, and Soliton, and has ownership and/or shareholder interest in Cytrellis.
Drugs commonly used to treat erectile dysfunction (ED) are not associated with a decreased risk of Alzheimer's disease and related dementias (ADRD), new research show.
The findings contradict findings from a previous study that suggested that individuals who take sildenafil (Viagra) were significantly less likely to develop Alzheimer's.
The new research, part of a larger effort to identify existing medications that could be repurposed to treat ADRD, employed a study design that reduced the risk for potential bias that may have influenced the earlier findings, the investigators note.
"That study came out last fall and was widely covered in the media, and we thought there were some methodological shortcomings that might have explained the results," lead investigator Rishi Desai, PhD, assistant professor of medicine at Harvard Medical School and an associate epidemiologist at Brigham and Women's Hospital, told Medscape Medical News.
The new study was published online October 4 in Brain Communications.
Animal studies suggest that phosphodiesterase-5 (PDE5) inhibitors, a drug class that includes the ED drugs sildenafil and tadalafil (Cialis), improve memory and cognitive function and reduce amyloid burden. But studies in humans have yielded conflicting results.
Although the new research and the work published last year both drew on Medicare data, they examined different patient populations.
The first study compared those who took sildenafil for any reason to those who did not take it. That design likely resulted in an analysis of a comparison of individuals with ED ― the most common indication for sildenafil ― to generally older individuals with diabetes or hypertension, Desai said.
In contrast, the current study included only those with pulmonary arterial hypertension (PAH), which is also an indication for PED5 inhibitors. The researchers compared ADRD incidence in those who took PED5 inhibitors to the incidence among those who took a different medication to treat their PAH. They used propensity matching to create two groups with similar characteristics and examined the data using four analytic strategies.
The investigators found no significant difference between groups in the incidence of ADRD, regardless of the strategy they used. Cell culture studies also revealed no protective effect from PED5 inhibitors.
"No study of this kind should claim the final word," Desai said. "It is extremely difficult to nail down causality from these types of data sources."
Commenting on the findings for Medscape Medical News, David Knopman, MD, professor of neurology at Mayo Clinic, Rochester, Minnesota, described the study design as "impressive" for its efforts to minimize bias, a key limitation in the previous study.
"It was always the case that the claims about sildenafil needed further developmental work prior to testing the drug in randomized controlled trials," Knopman said. "The evidence for the use of the drug was never sufficient for clinicians to use it in their patients."
The study was funded by National Institute on Aging. Desai is an investigator who receives research grants from Bayer, Vertex, and Novartis that were given to the Brigham and Women's Hospital for unrelated projects. Knopman has disclosed no relevant financial relationships.
Brain Commun. Published online October 4, 2022. Full text
Researchers have identified two distinct symptom trajectories in nondialysis dependent patients with moderate to severe, stage 3 to 5, chronic kidney disease (CKD).
Close to a third of the patients (31%) had very severe symptoms — notably fatigue and muscle pain — at baseline that worsened over time, and the remaining 69% of patients had less severe symptoms at baseline that remained stable, during a median 5.3-year follow-up.
Clinicians should perform "a systematic assessment of symptoms [in patients with CKD] by a validated questionnaire for planning early therapeutic interventions," the researchers advise, adding that "large gains may be achievable with greater provider appreciation of the importance of symptoms."
They call for "future research to assess the modifiable factors that affect the unfavorable symptom trajectory and other aspects of quality of life."
The study by Moustapha Faye, MD, and colleagues was published online October 28 in the Clinical Journal of the American Society of Nephrology.
In an accompanying editorial, Giselle Rodriguez de Sosa, MD, and Mark Unruh, MD, from the University of New Mexico, Albuquerque, write: "In addition to disease management," this "important study" provides "further evidence of the need to care for the unpleasant symptoms that cause suffering and affect the well-being of patients with advanced CKD."
Many current treatment regimens and medications may have unintended adverse consequences that contribute to reduced quality of life, they note.
"It is now more relevant to assess different patients at different stages" of CKD and target high-risk trajectories early on, with interventions to alleviate distress and poor quality of life, and not just avoid progression to a terminal stage," according to the editorialists.
There is little information about evolving symptoms in patients with different stages of CKD, and the few studies of patients who were not on dialysis have inconsistent findings, write Faye, of Centre Hospitalier Régional Universitaire [CHRU], Nancy, France, and Cheikh Anta Diop University of Dakar, Senegal, and colleagues.
They hypothesized that individuals with eGFR < 60 mL/min/1.73 m2 could be classified into subgroups based on their symptoms.
The patients were part of the CKD–Renal Epidemiology and Information Network (CKD-REIN), a nationally representative cohort of patients in France.
Researchers identified 2787 patients in the CKD-REIN cohort who had been diagnosed with CKD, had an eGFR <60 mL/min/1.73 m2, were not on kidney replacement therapy (dialysis or awaiting transplant), and had been seen by a nephrologist from July 2013 to March 2016 and followed until December 2020.
Patients were given a Kidney Disease Quality of Life-36 questionnaire (KDQOL-36) to complete at baseline and at 1, 2, 3, and 5 years.
Participants were a mean age of 67 years and 66% were men. They had a mean eGFR of 33 mL/min/1.73 m2 and 45% had stage 4 or 5 CKD.
The KDQOL-36 questionnaire asked patients to report how much they were bothered (not at all, a little, moderately, a lot, or very much) by 11 symptoms: chest pain, cramps, dry skin, faintness/dizziness, fatigue, itchy skin, lack of appetite, muscle pain/soreness, numbness in hands/feet, nausea/upset stomach, and shortness of breath.
During the study follow-up, 31%, 19%, 15%, and 15% of study participants completed five, four, three, and two KDQOL-36 questionnaires, respectively
Almost all patients (98%) reported at least one symptom. The most common symptoms were fatigue (83% of patients), muscle pain/soreness (82%), cramps (72%), dry skin (60%), and shortness of breath (68%). The least common symptom was chest pain (24%).
The researchers used a statistical model to identify two distinct symptom score trajectories, taking into account study dropouts due to kidney replacement therapy or death.
During follow-up, 690 patients started kidney replacement therapy and 490 patients died.
Patients in the "worsening symptoms" group deteriorated by more than 10 points (on a scale of 1 to 100).
The 31% of participants in the "worse symptom score and worsening trajectory" group had more baseline risk factors for CKD progression (eg, diabetes and obesity), a worse quality of life, and a higher probability for either kidney replacement therapy or death before kidney replacement therapy compared with the 69% of patients in the "better symptom score and stable trajectory" group.
CKD-REIN is funded by the Agence Nationale de la Recherche and also supported by different public-private partnerships with industry, over the years, as listed with the article. The author and editorialist disclosures are available with the publications.
Clin J Am Soc Nephrol. Published online October 28, 2022. Abstract, Editorial
Patients hospitalized with severe COVID-19 and no prior history of thyroid dysfunction show signs of thyroiditis that, although asymptomatic, continue to persist for up to a year after infection, according to research that adds to evidence on the complex involvement of the thyroid in COVID-19.
"To our knowledge these findings are novel," first author Ilaria Muller, MD, PhD, an assistant professor in endocrinology in the Department of Clinical Sciences and Community Health, University of Milan, Italy, told Medscape Medical News.
"Little has been written about the long-term follow-up of thyroid function after severe COVID-19 disease and we have followed patients up to 1 year after infection."
The effects are seen in about 10% to 15% of patients, and "[while] the thyroid dysfunction is transient, ultrasound areas of thyroiditis may persist after 1 year, even if they progressively shrink," said Muller, who presented the findings at the American Thyroid Association (ATA) 2022 Annual Meeting.
The nature and implications of the persistent thyroiditis areas are uncertain, Muller noted. "These areas of thyroiditis are likely a sort of 'immunologic scar' of the previous SARS-CoV-2 infection," she explained. "We still don't know if there are clinical implications, even if they seem unlikely."
Of note, increases in autoimmune processes or a higher incidence of thyroid dysfunction after COVID-19 have not been observed, and the shrinkage of the areas of thyroiditis over time is encouraging, she said.
The reasons why some patients develop atypical thyroiditis and others don't are also unclear, with Muller's team investigating further. Importantly, similar effects have been associated with other severe infections, not just COVID-19. "It is well known that in classic subacute thyroiditis due to other viral infections, the areas of thyroiditis persist for months, so this phenomenon might not be unique to COVID-19," she explained.
Commenting on the story, Jeffrey R. Garber, MD, also noted that such thyroiditis areas stemming from other types of infection may persist — but go unnoticed.
"Resolution is the clinical rule, [and] we generally do not restudy in detail those who clinically recover," he told Medscape Medical News. "However, there is evidence of impaired thyroid reserve in those who recover from viral thyroiditis due to other sources."
"Thyroid symptoms are often not specific, so 'atypical' [cases] are common, [and] resolution with restoring thyroid status to normal is mixed," noted Garber, an associate professor of medicine at Harvard Medical School and chief of the Division of Endocrinology at Atrius Health in Boston, Massachusetts.
In terms of clinical practice, while such issues should be kept in mind when evaluating abnormal thyroid tests during severe COVID-19, "it is not a call for routinely checking it in the absence of clinical suspicion," he observed.
Muller and her team previously observed that patients hospitalized in intensive care with COVID-19 often had low or suppressed serum thyroid-stimulating hormone (TSH) levels, with and without elevated free thyroxine concentrations, suggestive of thyrotoxicosis.
Upon investigating those cases, they found, as in their previous study reported by Medscape Medical News, that a painless, atypical thyroiditis occurs with nonthyroidal illness syndrome among patients hospitalized with severe COVID-19. The atypical thyroiditis was slightly more common in men and was associated with lymphopenia.
To further investigate those cases and follow patients up to 1 year, the team conducted a longitudinal study of 183 patients hospitalized with severe COVID-19 in Italy. The patients, who had no known prior history of thyroid dysfunction, were assessed for serum thyroid function, autoantibodies, and inflammatory markers.
At baseline, 10% of the patients were found to have thyrotoxicosis, and ultrasound performed within 2 to 3 months post-infection on 65 patients showed that 18 (28%) had areas of thyroiditis.
Importantly, 60% of those patients with the areas of thyroiditis had low TSH levels, while 25% had normal TSH levels (P = .034).
In addition, those showing the presence of thyroiditis on ultrasound at 2 to 3 months were more likely to have elevated serum concentrations of FT4 (P = .018) and higher levels of interleukin-26 (P = .016), compared with those with normal ultrasound readings.
In a longitudinal analysis further following patients post-infection, among 15 patients who were evaluated at 6 months, most, 13 (87%), still had areas of thyroiditis, and 6 of 12 (50%) had thyroiditis areas that, though reduced in size, still persisted even at 12 months.
In terms of thyroid uptake, at 3 months, 14 of 17 patients (82%) had diffused or focal areas of a reduction of uptake. After 6 months, there was a recovery, with a median of 28% of thyroid uptake recovered, however, 67% of patients still had some focal or diffused reduction in thyroid uptake.
Of note, the indications of thyroiditis on imaging persisted even though patients' TSH levels had quickly normalized at the end of infection and remained normal up to 1 year of follow-up.
The patients showed no apparent development of thyroglobulin antibody, thyroid peroxidase antibodies, or TSH receptor antibodies.
A further fine needle aspiration (FNA) analysis of eight patients with atypical thyroiditis at 3 months after infection showed that those patients had tissue resident memory T cells (CD4+/CD8+/CD103+/CD69+) within the thyroid, but not in the blood as expected.
Additional assessments at 8 months after infection showed those tissue resident memory T cells continued to be present on imaging.
The results showed "SARS-CoV-2-specific T cells were enriched within the thyroid compared with the blood, many with a tissue resident phenotype," Muller explained.
The findings are notable in that "such an in-depth characterization of areas of thyroiditis triggered by SARS-CoV-2 infection combining ultrasound, scintigraphy, and immunological phenotyping has not been performed so far," she said.
"In particular, SARS-CoV-2 specific tissue-resident memory T lymphocytes have not been described before in the thyroid gland."
Muller and Garber have reported no relevant financial relationships.
ATA 2022 Annual Meeting. Oral Abstract 12. Presented October 21, 2022.
The implications of the Inflation Reduction Act of 2022 (IRA), which is aimed at lowering the price of prescription drugs, are already reverberating across biopharma pipelines as companies hint at – or explicitly state – their impacts.
The IRA, which Pres. Biden signed into law in August, initially focuses on negotiating the prices for Medicare Part D’s 10 most-prescribed medicines and takes effect in 2026.
Prior to the bill’s passage, Merck CEO Robert Davis said the legislation on pricing would be “highly chilling on future innovation." The Biotechnology Innovation Organization (BIO) claimed the impact on drug manufacturers' revenue would make investment in R&D and innovation less attractive.
The most immediate impacts of the IRA are expected to apply to currently marketed drugs covered by Medicare. The Secretary of Health and Human Services (HHS) will have the power to negotiate the prices for 10 drugs by 2026; this will increase to 20 in 2029.
As companies reevaluate their pipelines accordingly, the Congressional Budget Office estimated the new regulation will lead to a 1% decline in newly approved drugs over the next decade.
However, this may "significantly underestimate" the impact as the CBO study only looks at newly approved drugs and does not account for reduced investment in life cycle management, according to Pharmaceutical Research and Manufacturers of America (PhRMA).
In Alnylam’s Q3 report Thursday, the company announced it would not initiate a Phase III trial for vutrisiran in Stargardt disease. Christine Lindenboom, SVP of investor relations and corporate communications at Alnylam, told BioSpace the company’s decision is related to the drug's Orphan Drug designation status.
Negotiation exemptions exist for drugs that have indications associated with only one Orphan Drug designation. Alnylam’s vutrisiran has Orphan designation in ATTR amyloidosis. If the Stargardt program were to move forward, it could ultimately negate the current exemption.
Companies may be incentivized to prioritize multiple assets with few targeted indications rather than “pipeline-in-a-product” development programs, since “multi-indication blockbusters are likely to face increased pricing scrutiny,” according to global strategy consultancy L.E.K.
This increased scrutiny would be expected to apply to Sanofi's pipeline cornerstone Dupixent. However, the company does foresee the impact from Medicare pricing negotiation taking effect prior to 2031, CEO Paul Hudson said during an investor call Friday.
Hudson was quick to reassure investors that the company is “well positioned in the short term to navigate the core elements related to” the IRA. He attributed this to the “industry-leading responsible pricing policy” Sanofi has followed for several years.
He added that Sanofi’s growth drivers are generally newer medicines and vaccines.
Hudson spoke to the potential impacts on the pharmaceutical industry in a broader sense.
“We believe that the implementation of these policies will likely create significant uncertainties across our industry with regards to sustainable investment in science and innovation and artificially influence future R&D decisions,” he told investors Friday.
Hudson went on to say that inflation penalties would “present a significant challenge to an industry dependent on a constant cycle of investments into innovation and expectations from others in the supply chain for additional rebates and fees.”
https://www.biospace.com/article/sanofi-alnylam-q3-reports-hint-at-early-pipeline-impacts-from-ira-/
