NJ Adds MTA As Defendant In Lawsuit Over Planned NYC "Congestion Fee"

 New Jersey Governor Phil Murphy has added New York’s Metropolitan Transportation Authority to an amended lawsuit complaint that the state had filed against the US Department of Transportation.

The lawsuit has argued that New York’s plan to charge drivers a congestion fee for driving through Manhattan’s central business district is unconstitutional and discriminatory against New Jersey residents, Bloomberg reported Tuesday.

New Jersey argues in the revised complaint that the congestion pricing policy breaches the dormant commerce clause of the U.S. Constitution, the report says. This clause restricts states from implementing legislation that unfairly discriminates or places excessive strain on interstate commerce.

According to Bloomberg, the lawsuit reads: “New Jersey will not receive any of the revenue from the tolling scheme. Instead, the congestion pricing scheme solely benefits in-state economic interests, the MTA Capital Program, based on revenue it receives from out-of-state commuters, including New Jersey residents.”

New Jersey is requesting both preliminary and permanent injunctions to prevent the MTA from carrying out construction or imposing new tolls related to the plan, as stated in the amended complaint.

This direct approach seeks to suspend the plan's progress and halt MTA's activities pending a more extensive environmental review.

On Tuesday, Governor Murphy said: “The federal government and the MTA can no longer be permitted to fast-track a proposal that solely benefits New York’s transportation system at the expense of hardworking New Jerseyans.”

The MTA plans to start tolling drivers by late May or June, with E-ZPass users paying $15 during peak times to access the area south of 60th Street in Manhattan. The toll is projected to generate $1 billion annually.

https://www.zerohedge.com/markets/new-jersey-adds-mta-defendant-lawsuit-over-planned-nyc-congestion-fee

MedPAC Report on Medicare Advantage Growth, High Costs Draw Fire

 A Medicare Payment Advisory Commission (MedPAC) meeting turned unusually contentious Friday as one member, Brian Miller, MD, MPH, of Johns Hopkins University in Baltimore, accused panel leadership of issuing a negative status report

opens in a new tab or window on Medicare Advantage (MA) plans' market dominance, saying it had been "hijacked for partisan political aims to justify a rate cut to Medicare Advantage plans."

Miller said the analysis, among a series of reports that advise Congress on Medicare policy, "appears to be slanted to arrive at a foregone conclusion in order to set up and provide political cover" just before the Centers for Medicare & Medicaid Services prepares its annual rate notice for MA plans, expected in coming weeks.

The chapter "reads like attack journalism as opposed to balanced and thoughtful policy research," Miller said during the commission's public meeting. He asked MedPAC staff to name three good things about MA plans, since he said none were in the report. He also criticized the report for numerous "intellectual inconsistencies" and "intellectual somersaults" and said it failed to make legitimate comparisons with care delivered to beneficiaries in fee-for-service.

The subject of his ire was a slide presentation that is posted for the public -- and a lengthy report that only commissioners can read -- highlighting growing concerns with the rapidly increasing amounts of Medicare funds now flowing to MA plans. The slides showed that MA plan "coding intensity" and "favorable selection" increased spending to MA plans -- $82 billion in 2023 alone -- above what Medicare paid for care to fee-for-service beneficiaries.

The analysis detailed the numerous ways that MA plans generate higher revenue, including enrolling people who are relatively healthy, known as favorable selection. They then vigorously scan patients' medical histories and charts to code for health factors that generate higher per-capita payments, known as coding intensity, often spending less on services. Coding intensity is also the difference between a risk score that a beneficiary would receive in an MA plan versus in fee-for-service.

The report said that coding intensity has increased over the years, with many of the biggest MA plans appearing to do the most. It also noted that a few plans now dominate the MA plan market, and that three companies -- UnitedHealthcare, Humana, and CVS Health -- enrolled 58% of all MA enrollees in 2023.

"Higher coding organizations have a competitive advantage because they receive larger payments for enrolling the same beneficiaries as other organizations, and they can offer more extra benefits and attract new enrollees simply because of their coding efforts," Andrew Johnson, PhD, MedPAC's principal policy analyst, told commissioners.

Pushback on the report also came from Better Medicare Alliance, which represents MA plans. In a press statement, President and CEO Mary Beth Donahue said the organization has "concerns about MedPAC's methodology and how its staff reached the report's conclusions." She noted that compared with fee-for-service, MA enrollees experience more benefits and savings; for example, they have 43% fewer avoidable hospitalizations and a 21% higher rate of seeing a physician within 14 days of discharge. Moreover, 99.9% of MA plans offer supplemental benefits.

Several commissioners came to the report's defense, noting that they appreciated the report's necessity and applauded its difficulty and complexity.

Many also chimed in with a wide array of adjacent frustrations they've heard about MA from providers and patients dealing with narrow networks, prior authorization practices that delay or deny care, and extravagant broker commissions that result in steering confused seniors into plans without their understanding of what they might be giving up.

A 'Sense of Urgency'

According to the report, 52% of beneficiaries -- 31.6 million people -- are now enrolled in MA plans, up from 26% in 2010, a fact that prompted many commissioners to note a "sense of urgency" that aspects of the MA program have gotten out of control.

"The reason I feel a sense of urgency is, we keep coming back to this issue that MA has never yielded aggregate savings to the Medicare program, despite that being one of the core goals," said Commissioner Cheryl Damberg, PhD, director of the RAND Center of Excellence on Health System Performance.

Lynn Barr, MPH, founder of Caravan Health, which was acquired by CVS Health through its acquisition of Signify Health, noted that "this is not the big lovely, you know, glowing success that everybody says it is. And we continue to create policies that drive people into these plans."

She referred to the fact that Medicare allows money paid to MA plans to be used for broker commissions as high as "$600 to recruit them, and they get $300 a year every year that they stay [in the MA plan]."

"We have allowed MA to buy the market," she added. "And that is why MA is growing. It's not because the quality's so great. People don't love the prior auth, people are leaving their plans a lot."

Aside from Medicaid, Medicare is the least profitable payer for doctors, Barr pointed out. "And at the same time, we give all this money to the plans. It's unconscionable."

Commissioner Larry Casalino, MD, PhD, of Weill Cornell Medicine in New York City, said that while policy experts maintain that MA plan growth is propelled by patient preferences, the real reason may be because of how brokers are pitching the plans to their clients.

"Increasingly, I get the sense they [brokers] have a pretty large role and they're paid quite a bit to enroll people in MA plans," he noted.

Casalino said that he and others have concerns about another disturbing practice that generates MA plan revenue. He's "heard in interviews frequently that physicians are paid directly as individuals to, in one way or another, cooperate with the health plans upping up the diagnostic codes. We've heard numbers like $100 per patient. I can't say whether that's true or not, but I don't think this is a trivial issue."

Wayne Riley, MD, MPH, president of State University of New York Downstate Health Sciences University in Brooklyn, New York, said that, in regards to MA plan quality, "we're hearing a crescendo of commentary around the country about [prior] authorizations being a big issue now ... from MA patients." He asked commission staff to prepare more information about which plans are using the practice the most.

Several commissioners pointed to how enormously complicated the process of choosing a Medicare option has become.

Gina Upchurch, RPh, MPH, executive director of the nonprofit Senior PharmAssist in Durham, North Carolina, said that providing counseling on Medicare benefits has become difficult. It's not just hospitals and doctors that someone has to be concerned about being in network with a plan, she said. Some MA plans may not include contracts for care at inpatient rehabilitation or skilled nursing facilities or home health agencies. Many aspects of plan differences have "gotten really complex," she added.

Stacie Dusetzina, PhD, of Vanderbilt University Medical Center in Nashville, Tennessee, noted that some MA beneficiaries may have trouble getting cancer care in MA plans' limited networks.

She referenced a recent news storyopens in a new tab or window about an MA enrollee who couldn't get the cancer care he needed from his MA plan, and couldn't get out of it without facing 20% in expensive copays. In all but four states, supplemental plans that could pick up the difference can reject patients with costly conditions.

"When you're 65 and aging into the program, you're healthy at that time, you may not be thinking about your long-term needs, which would push you to think harder about the specialty networks that you may have access to [in an MA plan] or not," she said.

In summary of the 2-hour session, Commission Chair Michael Chernew, PhD, of Harvard Medical School in Boston, acknowledged the numerous research challenges ahead for the agency, but said he believes MA plan enrollees receive similar, or even better, quality than fee-for-service beneficiaries.

However, he added, there could be changes over time, "and there's a ton of heterogeneity across plans," meaning that some may be delivering high-quality care, while others not so much.

He emphasized that the commission has not drawn any conclusions about MA plans going forward, but that the report simply acknowledges issues, such as higher payments, that MA plans receive. "We're just reporting the facts as we see them," he said.

https://www.medpagetoday.com/special-reports/features/108275

Overdose Death Notices Plus Guidance Sink Opioid Prescribing

 Physicians who received a letter from a medical examiner about a patient's fatal overdose -- along with suggested guidance for future visits for pain -- prescribed fewer opioids, according to a cluster randomized controlled trial.

Doctors who received the death notice plus guidance had a drop in weekly morphine milligram equivalents (MMEs) pre- to post-intervention (157.81 to 77.05), according to Jason Doctor, PhD, of the University of Southern California in Los Angeles, and colleagues.

While physicians who only got a death notice also saw a decline in weekly MMEs (157.70 to 103.16), those with the death notice plus guidance letter had a 12.85% greater decline in opioid prescribing (P<0.001), Doctor and colleagues reported in Nature Communicationsopens in a new tab or window.

"Providing physicians a simple plan that will guide them at a patient visit appears to help temper their use of these drugs," Doctor said in a press release. "This represents a promising approach to reducing fatal drug overdoses, one that is both affordable and scalable."

Doctor and colleagues noted that previous workopens in a new tab or window showed that notifying physicians by mail when a patient died of an opioid overdose helped diminish opioid prescribing. But they wanted to know whether adding "planning prompts" -- concrete actions that can be triggered by a specific set of circumstances -- could reduce this prescribing even further.

"For example, a physician might better use the information in the letter, if the letter guidance urges them to implement steps at the visit, such as discussing alternative pain management strategies or consulting with a pain management or addiction specialist for evaluation and care," the researchers wrote.

To conduct the trial, Doctor and colleagues randomized 541 clinicians in Los Angeles County to receive either a standard letter about the patient's death (n=284) or the letter with guidance (n=257).

Participants were included because they prescribed schedule II-IV drugs within the prior year to a patient who died of an overdose where opioids were a primary or contributing cause. Overall, 316 deaths from late October 2018 to late May 2020 were included.

Both physician groups received a letter signed by the examiner-coroner informing them of their patient's opioid-related overdose death and information about judicious prescription practices. The intervention group additionally received an "if/when-then" plan that explained alternative ways to handle patients who needed pain treatment. The letters were sent monthly between April 4, 2019, and July 8, 2020.

In addition to greater declines in opioid prescribing, doctors who received the additional "if/when-then" plan also had greater declines in benzodiazepine prescribing, with an 8.32% reduction in weekly diazepam milligram equivalents (P<0.001).

The study was limited because it may not be generalizable outside of Los Angeles County, the largest county in the U.S., and by its small sample size. It examined a short-term effect and did not follow up to determine any effects on patient outcomes.

Also, the intervention reached only prescribers with a death in their practice, though the researchers emphasized those clinicians were likely most in need of the intervention.

They called for further research "to confirm the results, examine the long-term effects of the intervention, and explore its potential effects on patient outcomes."

Doctor added that the study "is part of an evolution toward better understanding how to enact behavior change among physicians whose patients have suffered negative consequences from care by the medical community."

Disclosures

The study was funded by the National Institute on Aging.

The authors reported no relevant financial relationships.

Primary Source

Nature Communications

Source Reference: opens in a new tab or windowDoctor JN, et al 'A randomized trial looking at planning prompts to reduce opioid prescribing' Nat Commun 2024; DOI:10.1038/s41467-023-44573-5.

https://www.medpagetoday.com/psychiatry/opioids/108282

Gabapentinoids in COPD Patients May Raise Risk for Severe Exacerbations

 Gabapentinoid use in patients with chronic obstructive pulmonary disease (COPD) was associated with a higher risk for severe exacerbations, a population-based cohort study from Canada indicated.

Among more than 27,000 COPD patients, those who started therapy with the anticonvulsant for either epilepsy, neuropathic pain, or some other form of chronic pain had a 39% greater risk for severe exacerbations compared with a matched group of nonusers (HR 1.39, 95% CI 1.29-1.50), reported Christel Renoux, MD, PhD, of the Lady Davis Institute and Jewish General Hospital in Montreal, and colleagues in Annals of Internal Medicineopens in a new tab or window.

The findings were consistent across age, sex, and COPD severity, and the increased risk for severe exacerbations remained consistent across the three subgroups studied:

• Epilepsy: HR 1.58 (95% CI 1.08-2.30)
• Neuropathic pain: HR 1.35 (95% CI 1.24-1.48)
• Other chronic pain: HR 1.49 (95% CI 1.27-1.73)

"Public health agencies have released warnings of respiratory depressionopens in a new tab or window as a potentially serious adverse effect of gabapentinoids, including for patients with COPD," wrote Renoux and co-authors. "However, these directives are yet to be echoed in clinical practice guidelines for the management of COPD and of neuropathic pain."

"Several guidelines for the management of neuropathic pain recommend gabapentinoids as first-line pharmacotherapeutic options," they continued. "Although one guideline noted gabapentinoids' potential for misuse and dependence, none mentioned the potential for respiratory adverse effects. Thus, our findings may help inform the prescription of gabapentinoids in patients with COPD."

On- and off-label gabapentinoid prescriptions are on the riseopens in a new tab or window across North America, partly in response to the opioid epidemic, the authors suggested, given that the class of drugs are often perceived as a safer alternative to opioidsopens in a new tab or window.

"These trends are of concern because gabapentinoids are not effective in many of these off-label indications, yet they expose patients to potentially serious adverse effects," Renoux and co-authors noted. "In particular, their propensity to cause central nervous system depression leading to sedation and respiratory depression has been reported in both animal and human studies."

The analysis used three digital health insurance databases in Quebec and included 13,504 COPD patients ages 55 and older exposed to gabapentinoid from 1994 to 2015 for either epilepsy (n=356), neuropathic pain (n=9,411), or other chronic pain (n=3,737). These patients were matched to an equal number of COPD patients with epilepsy, neuropathic pain, or other chronic pain but who were not exposed to gabapentinoids.

The study's main outcome was a severe COPD exacerbation requiring hospital admission or resulting in death.

For secondary outcomes, gabapentinoid use was also associated with an increased risk for either moderate or severe exacerbations, as well as respiratory failure, in patients taking the drugs for neuropathic or other chronic pain. Precision was limited regarding this association in patients with epilepsy, the researchers reported.

COPD was defined by relevant medications for the condition based on ICD codes, which included the possibility of misclassification if patients were prescribed long-acting beta-agonist/inhaled corticosteroids for asthma.

Other limitations included that data on race/ethnicity were missing, as were details on smoking status, and that the study may have captured more patients ages 65 and older, "because all persons in this age group are insured for prescription medication in Quebec," Renoux and colleagues said.

Disclosures

The study was funded by grants from Boehringer Ingelheim Canada/CIHR-ICRH, the Canadian Lung Association, and the Canadian Institutes of Health Research (CIHR).

Renoux disclosed relationships with the Canadian Lung Association and CIHR. Co-authors disclosed relationships with pharmaceutical companies and other organizations.

Primary Source

Annals of Internal Medicine

Source Reference: opens in a new tab or windowRahman AA, et al "Gabapentinoids and risk for severe exacerbation in chronic obstructive pulmonary disease - a population-based cohort study" Ann Intern Med 2024; DOI:10.7326/M23-0849.

https://www.medpagetoday.com/pulmonology/smokingcopd/108283

Lives Prolonged for Longtime CRT-D Users With Heart Failure

 Eligible heart failure patients with a wide QRS complex spent more time alive after use of a cardiac resynchronization therapy defibrillator (CRT-D) compared with an implantable cardioverter-defibrillator (ICD), according to long-term results of the RAFT trial.

Survivors with nearly 14 years of follow-up continued to tilt the study's all-cause mortality rates in favor of CRT-D (71.2% vs 76.4% with ICD). Time until death was significantly different between the two randomly assigned therapies (acceleration factor 0.80, 95% CI 0.69-0.92), reported a group led by John Sapp, MD, of Dalhousie University in Halifax, Nova Scotia.

A secondary outcome, the composite of death from any cause, heart transplantation, or implantation of a ventricular assist device, was also less likely with a CRT-D compared with ICD therapy (75.4% vs 77.7%, acceleration factor 0.85, 95% CI 0.74-0.98), the investigators noted in the New England Journal of Medicineopens in a new tab or window.

"Because CRT offers remarkable improvements in functional capacity, quality of life, and survival, the principles of providing earlier treatment for heart failure might now include CRT, particularly as technology improves," wrote Lynne Warner Stevenson, MD, and Jay Montgomery, MD, both of Vanderbilt University Medical Center in Nashville, in an accompanying editorialopens in a new tab or window.

A CRT-D, also called a biventricular pacemaker, has electrodes going to both the right and left ventricles so that a pulse generator can signal them to pump with correct synchrony.

The RAFT study's initial report from 40 monthsopens in a new tab or window showed that the addition of CRT to an ICD reduced rates of death and hospitalization for heart failure -- albeit with more complications such as lead dislodgement, device-pocket infection, and coronary sinus dissection compared with standard ICD therapy.

Stevenson and Montgomery highlighted the benefits of CRT-D on top of heart failure medications that were standard at the time RAFT was enrolling in the 2000s. They also noted that clinical improvements could be detected "despite patient crossover from the ICD group to the CRT-D group and the inclusion of some patients who did not have a left bundle-branch block on electrocardiography and other patients who did not meet the current criteria for CRT."

Since RAFT and other trials such as MADIT-CRTopens in a new tab or window and CARE-HFopens in a new tab or window, CRT-D therapy has won some overlapping indications with ICDs.

"Enthusiasm for CRT therapy in patients with mild heart failure is likely to increase further with recent data suggesting equal or better clinical outcomes with direct left bundle-branch area pacing instead of placement of the CRT leads through the coronary sinus," Stevenson and Montgomery predicted. "Further advances in the design of pacing leads and delivery sheaths should improve the physiologic response to CRT and reduce procedural complications."

The RAFT investigators had enrolled a total of 1,798 patients with New York Heart Association (NYHA) class II or III heart failure, a left ventricular ejection fraction of 30% or less, and an intrinsic QRS duration of 120 msec or more (or a paced QRS duration of 200 msec or more).

"CRT has been shown to result in significant improvement in cardiac performance and to lead to reverse remodeling, a reduction in new-onset ventricular arrhythmias, and improved clinical outcomes. It is possible that these beneficial early effects may be associated with the much longer-term improvements in overall survival shown in our trial," Sapp and colleagues surmised.

Pulling the subgroup of patients enrolled at the eight highest-enrolling sites out of 34 participating centers, the present long-term analysis included 1,050 people. The study population had a median 7.7 years of follow-up split between survivors and non-survivors. The survivors had data out to 13.9 years.

Mean age was just over 66 years, and over 80% of patients were men. Just under a quarter had NYHA class III symptoms at baseline. Additionally, 15.7% had a persistent atrial arrhythmia, 70.2% had left bundle-branch block, and 8.4% had right bundle-branch block.

Among the trial's limitations was its lack of accounting for crossovers between groups and the low representation of women and different races, Sapp and colleagues acknowledged.

"Since the initial trial was completed, pharmacologic therapy for heart failure has advanced, with the introduction of neprilysin inhibitors and [SGLT-2] inhibitors. CRT improves cardiac performance without increasing cardiac work and would be anticipated to have a complementary effect to pharmacotherapy; however, the influence of CRT on survival for patients treated with newer drugs is uncertain," they cautioned.

Disclosures

The trial was sponsored by Ottawa Heart Institute Research Corporation.

Sapp reported relationships with Abbott, Johnson & Johnson, Medtronic, and Varian Medical Systems.

Stevenson and Montgomery had no disclosures.

Primary Source

New England Journal of Medicine

Source Reference: opens in a new tab or windowSapp JL, et al "Long-term outcomes of resynchronization-defibrillation for heart failure" N Engl J Med 2024; DOI: 10.1056/NEJMoa2304542.

Secondary Source

New England Journal of Medicine

Source Reference: opens in a new tab or windowStevenson LW, Montgomery JA "Seeking more time with synchrony" N Engl J Med 2024; DOI: 10.1056/NEJMe2312419.

https://www.medpagetoday.com/cardiology/chf/108290

How Should Health Plans Respond to Surging Interest in Weight Loss Drugs?

 Since the NIH started measuring obesity prevalence in the U.S. 60 years ago, the rates have tripled

opens in a new tab or window, with more than 42% of American adults considered obese and another 31% overweight. As excess weight is linked to chronic conditions like diabetes, hypertension, and congestive heart failure, healthcare providers and patients alike are looking for long-term solutions to reduce risks.

Treatments for obesity have historically been expensive and invasive (such as bariatric surgery), or ineffective, deterring insurers from addressing obesity as a chronic condition. But when Eli Lilly's tirzepatide (Mounjaro) and Novo Nordisk's semaglutide (Ozempic) hit the market to fight diabetes, these drugs also achieved impressive weight loss results for diabetic patients with obesity. Despite their indication for patients with diabetes, many people have been using these drugs off-label to accomplish significant weight loss unrelated to diabetes treatment.

Yet, with an increasing number of FDA-approved GLP-1 receptor agonists indicated for overweight or obesity -- the latest approval being tirzepatide (Zepbound)opens in a new tab or window -- the question still remains: Will these drugs be covered by insurance? In cases where health plan sponsors (employers) contract with a full-risk health insurance company, it's up to the health insurance company to determine coverage. In other cases -- for example, when self-insured plan sponsors contract with a third-party administrator -- it's up to the plan sponsor (or federal law).

Health insurance companies and plan sponsors are facing an important decision about whether to cover these drugs as a treatment for obesity.

Growing Interest in Weight-Loss Drugs

In a recent poll, the Kaiser Family Foundation found that nearly halfopens in a new tab or window of adults (45%) say they are generally interested in taking a prescription weight-loss drug, but that percentage drops to 16% if the medication is not covered by insurance.

These drugs are expensive; retail prices average around $1,000opens in a new tab or window for a month of injections. But the results are hard to ignore. In one clinical studyopens in a new tab or window, tirzepatide helped patients lose an average of 26.6% of their body weight following extended use and lifestyle changes. Unlike previous studies, these trials excluded people with type 2 diabetes.

The benefits of tirzepatide and semaglutide extend beyond weight loss to the improvement of other health conditions. In November 2023, another clinical studyopens in a new tab or window showed that semaglutide can reduce the risk of heart attacks and stroke by 20% for adults with heart disease and obesity.

Studies like these support the proposition that health plan coverage of the drugs is warranted.

Pay Now or Pay Later?

As most doctors and health insurers are aware, obesity is associated with a variety of health problems, including susceptibility to heart disease, stroke, and musculoskeletal issues. But is the investment in covering these drugs worth the benefit of improving long-term health? Weight-loss treatment offers the potential to protect against expensive and debilitating health conditions in the future, but what about the impact on costs now?

Currently, most private insurance and federal programs don't cover drugs like tirzepatide and semaglutide for weight loss because of their high cost. Additionally, Medicare is prohibitedopens in a new tab or window by law from covering weight-loss drugs because of lingering safety concerns that stem from the legacyopens in a new tab or window of drugs like fenfluramine and phentermine (fen-phen).

However, we advise approaching obesity as a chronic condition that requires long-term treatment and maintenance, including potential long-term or even lifetime use of drugs like semaglutide or tirzepatide. Notably, many physicians are now likely to prescribe weight-loss drugs in addition to weight management programs that include nutrition education, lifestyle changes, and behavior modification. Self-insured employers and insurance carriers must balance clinical and financial outcomes in making the decision on whether to cover these drugs for weight loss.

If health insurance carriers and self-insured employers decide that covering these drugs is in the best interest of their members, they may want to incorporate strict eligibility requirements.

For example, semaglutide (Wegovy) is intendedopens in a new tab or window for use by patients with a BMI of 30 or greater, or a BMI of 27 or greater and one weight-related health condition, such as high blood pressure. Recently, the FDA approved the use of Zepbound with the same eligibility requirementsopens in a new tab or window. When considering coverage of weight-loss drugs, health insurance carriers and self-insured employers may want to implement similar restrictions.

Because these drugs are so new, it's hard to make a conclusive financial case that covering them is cost-effective in the long term. But given the clinical trials that show benefits far beyond diabetes control, the clinical case for covering weight-loss drugs, at least for certain populations, is becoming more compelling than ever.

Nancy K. Klotz, MD, MBA,opens in a new tab or window is Chief Medical Officer at Brighton Health Plan Solutions, LLCopens in a new tab or window, a third-party health insurance administrator that provides administrative services for self-funded health plans. She is responsible for clinical strategy across the company's various business segments. Klotz is a fellow of the American College of Physicians.

https://www.medpagetoday.com/opinion/second-opinions/108268

'Novel Antiviral Shortens COVID Illness in Outpatients, Reduces Viral Load'

 With oral simnotrelvir/ritonavir treatment in a vaccinated population, COVID-19 symptoms went away about 1.5 days earlier and SARS-CoV-2 viral loads fell, a Chinese placebo-controlled phase II/III trial found.

In patients with mild-to-moderate COVID-19, the median time to sustained symptom resolution was significantly shortened from 216 hours to approximately 180 hours when simnotrelvir/ritonavir was taken within 72 hours of symptom onset and continued twice daily for 5 days (P=0.006), Bin Cao, MD, from the China-Japan Friendship Hospital in Beijing, and colleagues reported.

Also by day 5, simnotrelvir/ritonavir significantly decreased the SARS-CoV-2 viral load from baseline when compared to placebo (mean difference -1.51 log₁₀ copies/mL, 95% CI -1.79 to -1.24). Viral load reductions at day 7 and day 9 were also greater in the simnotrelvir/ritonavir group, the authors detailed in the New England Journal of Medicineopens in a new tab or window.

In the trial's subgroup with risk factors for severe COVID-19, simnotrelvir shortened median time to symptom resolution by 60.4 hours. Investigators found no safety concerns, though adverse events occurred in a greater proportion of patients in the simnotrelvir group.

Currently available antivirals for COVID outpatients, namely nirmatrelvir-ritonavir (Paxlovid)opens in a new tab or window and remdesivir (Veklury)opens in a new tab or window, are recommended for high-risk groups based on studies demonstrating their ability to reduce the risk for COVID-related hospitalization or death. But the drugs are associated with high out-of-pocket costs ever since the U.S. ended universal access to free COVID treatments last year.

"Because of the high costs of the drugs and inequity in their distribution, more drug options are needed to accelerate the resolution of symptoms among patients with mild-to-moderate COVID-19," Cao and co-authors wrote.

Simnotrelvir, an oral 3-CL-like protease inhibitor, has received emergency conditional authorization in China for mild-to-moderate COVID-19, though any plans for regulatory approval in the U.S. are unclear.

"I think we have to be interested -- and even a bit excited -- about these results, but we should like to see them applied in the population of greatest interest," said William Schaffner, MD, of Vanderbilt University in Nashville, Tennessee, in an interview with MedPage Today.

Schaffner, who was not involved in the study, pointed out that trial participants were relatively young, healthy, and vaccinated. "Some of them did have some cardiovascular disease, but this was not the population we're most concerned with who are older, who have one or more serious chronic underlying medical conditions."

And the trial was not designed to provide information on simnotrelvir's effects on outcomes of greatest clinical relevance, Schaffner noted -- COVID-related hospitalization, ICU admissions, or mortality.

That said, he stressed that it is important to develop new COVID-19 treatments that have the potential to overcome some of the limitations of nirmatrelvir-ritonavir. "Having an alternative is always a good thing," he commented.

The trial enrolled over 1,200 patients from 35 sites in China from August to December 2022. Participants were adults with symptoms of mild or moderate COVID-19, most commonly sore or dry throat, cough, stuffy or runny nose, headache, and fever. Half were randomized to receive 750 mg simnotrelvir/100 mg ritonavir and half to a matching placebo, twice daily for 5 days.

For this analysis, Cao's group relied on the 1,007 people in the modified intention-to-treatment cohort who received their assigned treatment within 72 hours of symptom onset. Nearly half received the trial drug or placebo within 48 hours.

Patients were quarantined, observed, and assessed for treatment adherence in designated hospitals. Patients provided self-assessment of COVID-19 related signs and symptoms on a subjective scale. Investigators quantified SARS-CoV-2 RNA from nasal or oropharyngeal samples obtained at regular intervals through day 29.

Study authors reported that the trial population had a median age of 35 years, with 59% being men. A majority (53.5%) had a risk factor for severe COVID-19, including overweight or obesity (35.7%), current or former smoking (22.7%), and cardiovascular disease (4.5%). Approximately 96% were vaccinated for COVID-19 and 77% had received a booster vaccination.

Other secondary endpoints showed that treatment with simnotrelvir/ritonavir shortened the median time to sustained alleviation of symptoms by about 48 hours and accelerated the resolution of respiratory symptoms by about 41 hours.

Adverse events occurred in 17.5% of patients in the simnotrelvir group and 10.2% in the placebo group. The three most common drug-related adverse events were an increase in triglyceride levels (4.3%), a decrease in neutrophil count (1.9%), and diarrhea (1.7%). No patients died during the trial period.

Disclosures

The study was funded by Jiangsu Simcere Pharmaceutical.

Cao and some co-authors reported consulting for Jiangsu Simcere Pharmaceutical. Co-authors also included employees of the company.

Schaffner reported no ties to industry.

Primary Source

New England Journal of Medicine

Source Reference: opens in a new tab or windowCao B, et al "Oral simnotrelvir for adult patients with mild-to-moderate COVID-19" N Engl J Med 2024; DOI: 10.1056/NEJMoa2301425.

https://www.medpagetoday.com/infectiousdisease/covid19/108300