Search This Blog

Thursday, September 21, 2023

ARS vows to appeal surprise FDA rejection for epinephrine nasal spray

 Positive FDA advisory committee votes aren’t always a blueprint for approval. ARS Pharmaceuticals learned that lesson the hard way Tuesday, after the FDA issued a surprise rejection of its anaphylaxis nasal spray Neffy.

The FDA has slapped down Neffy, also known as epinephrine nasal spray, to treat type I allergic reactions, including anaphylaxis for adults and children, ARS said in a press release. Given that the drug passed muster at a recent meeting of the FDA’s Pulmonary-Allergy Drugs advisory committee (PADAC), ARS plans to submit a formal dispute resolution request to appeal its complete response letter (CRL).

The FDA is asking ARS to provide more study data on repeat doses of Neffy compared to repeat doses of injectable epinephrine for allergen-induced allergic rhinitis conditions, ARS said.

PADAC in May voted to approve Neffy without the need for additional efficacy or safety studies, the company points out.

In another blow to ARS, the company had already aligned with the FDA in August on final labeling and a post-marketing study plan.

“We are very surprised by this action and the late requirement at this time to change the repeat-dose study from a post-marketing requirement, which we had previously aligned on with FDA, to a pre-approval requirement, particularly given the positive Advisory Committee vote,” Richard Lowenthal, co-founder, president and CEO of ARS Pharma, said in a statement.

Some analysts, such as William Blair’s Tim Lugo, agreed with the company. In a note to clients, Lugo wrote that because of prior interactions with the FDA and the positive advisory committee vote, “this decision comes as a surprise.”

The study requirements are poised to “complicate what has already been a long development process,” Lugo added.

“It does raise questions of whether the agency really wants to approve the therapy, as the pathway has already far exceeded epinephrine products such as EpiPen,” he continued.

Because ARS already agreed to a repeat-dose study as a post-marketing condition, the company expects to resubmit its Neffy application in the first half of 2024, which would set it up for an FDA decision in the second half of next year.

With expectations to have roughly $195 million in cash on hand at the time of the anticipated launch, ARS is “well capitalized to endure the delay,” William Blair’s Lugo said.

https://www.fiercepharma.com/pharma/ars-pharmaceuticals-hit-surprise-fda-rejection-nasal-spray-epinephrine-alternative

'Inhaled Glucocorticoid Flops for Speeding COVID Recovery in Outpatients'

 Inhaled fluticasone furoate failed to shorten recovery time for non-hospitalized adults with COVID-19, new data from the adaptive ACTIV-6 trial found.

When used daily for 2 weeks, a quicker COVID-19 recovery time -- considered at least 3 consecutive days without symptoms -- was no more likely with fluticasone furoate than with placebo (HR 1.01, 95% CI 0.91-1.12), according to Susanna Naggie, MD, MHS, of Duke University School of Medicine in Durham, North Carolina, and colleagues.

Yet a numerically higher rate of urgent care/emergency department visits and hospitalizations was observed in the fluticasone furoate group (3.7% vs 2.1%, respectively; HR 1.90, 95% CI 0.90-3.50), the researchers reported in the New England Journal of Medicine

opens in a new tab or window.

Combined, the lack of treatment effect and that possible increase in healthcare usage suggest that the inhaled glucocorticoid is "not a favorable" therapy for COVID-19, wrote Naggie and co-authors.

But the negative results didn't come as a shock to William Schaffner, MD, of Vanderbilt University in Nashville, Tennessee, who was not involved with the study.

"It was a very good idea and a nice try, but we have been trying to either treat or prevent COVID and other respiratory viruses by interrupting their capacity to multiply on the surface of the respiratory epithelium for a while, and we haven't figured it out yet," Schaffner told MedPage Today.

Searching for a repurposed drug for COVID-19 is "a worthy goal, but a high-risk venture," Schaffner said. When one is found, its side-effect profile is likely to be well-understood and it could potentially be cheaper.

Thus far, inhaled glucocorticoids have demonstrated mixed efficacy in treating COVID outpatients, with some benefit for shortening recovery time seen with inhaled budesonide in the PRINCIPLE study

opens in a new tab or window, which enrolled a considerably older population than ACTIV-6 (mean age 65 vs 47 years).

While the dose of fluticasone furoate used in the current study is about four times more potent than the budesonide dose in PRINCIPLE (and has a longer half-life), they are "different glucocorticoids, and there could be a budesonide-specific effect," Naggie's group pointed out.

In light of a recent meta-analysisopens in a new tab or window confirming the efficacy of nirmatrelvir/ritonavir (Paxlovid) and molnupiravir, Schaffner said those two oral medications are still the best option for high-risk outpatients with COVID-19.

"Older persons and people with underlying illnesses and those who are immune-compromised are still getting Paxlovid, and there is a general sense that this is helping keep people out of the hospital," he said.

ACTIV-6, part of the National Institutes of Health's ongoing decentralized Accelerating COVID-19 Therapeutic Interventions and Vaccines

opens in a new tab or window trial, aims to test the effectiveness of repurposed drugs in reducing the duration and severity of symptoms associated with mild-to-moderate COVID-19. Prior results from ACTIV-6 specifically have shown no benefit with the antiparasitic ivermectinopens in a new tab or window or the depression drug fluvoxamineopens in a new tab or window versus placebo.

The current study included 1,277 patients, with roughly half assigned to the study drug or placebo. Patients entered the trial a mean of 5 days after symptom onset (but no more than 7 days) and had at least two infection symptoms. Some had already received therapeutics, including remdesivir (0.1%), a monoclonal antibody (2.4%), or nirmatrelvir/ritonavir (0.1%).

Median participant age was 45 years, more than 60% were women, with about 80% white, 7.1% Black, 5% Asian, and 12.6% Hispanic. Comorbid conditions included diabetes (9.7%), hypertension (26.1%), and asthma (13%).

Overall, the mean number of days unwell was 11.2 in the fluticasone furoate group and 11.3 in the placebo group. There were three hospitalizations and no deaths through day 28 in each group.

Investigators found no evidence of a positive treatment effect for fluticasone furoate by sex, timing of symptom onset, severity of symptoms, body mass index, age, or calendar period.

About two-thirds were fully vaccinated against COVID-19. Among these 846 subjects, a trend toward a faster recovery time was seen favoring the fluticasone furoate intervention (HR 1.10, 95% CI 0.95-1.28).

Incidence of adverse events was similar in the two groups, experienced by 2% of the fluticasone group and 2.5% of the placebo group. The most common was COVID-19 pneumonia, which occurred in three subjects on fluticasone and one on placebo.

Disclosures

Naggie reported relationships with AbbVie, Bristol Myers Squibb, Gilead Sciences, the National Institutes of Health, Pardes, Personal Health Insights, Silverback, and Vir Bio. Co-authors reported various relationships with industry.

Primary Source

New England Journal of Medicine

Source Reference: opens in a new tab or windowBoulware DR, et al "Inhaled fluticasone furoate for outpatient treatment of Covid-19" N Engl J Med 2023; DOI: 10.1056/NEJMoa2209421.


https://www.medpagetoday.com/infectiousdisease/covid19/106424

'Medicare Advantage Ads Should Look Different This Year'

Last week, CMS administrator Chiquita Brooks-LaSure was in South Dakota listening to Native American tribal members explain how they were persuaded to enroll in Medicare Advantage (MA) plans whose networks -- they subsequently realized -- didn't include their local Indian Health Service providers.

"I hear regularly from patients and doctors when they have to delay their care, including significant procedures like surgeries, due to prior authorization or other rules" in MA plans, she said. "And [beneficiaries] may not have the understanding of the steps that they're going to have to take when they sign up for a Medicare Advantage plan."

While visiting a Michigan adult day center last year, she heard from seniors who were "being bombarded with phone calls" from MA sales representatives who confused them. The seniors all had questions but they didn't know who they could trust, she said.

Brooks-LaSure made her remarks during a Kaiser Family Foundation webinaropens in a new tab or window Wednesday that focused on misleading and deceptive MA plan marketing strategies that used celebrity actors or sports icons making exaggerated or false benefit claims on TV -- all to woo senior beneficiaries to sign up.

Things are going to be different with this year's ad campaigns before and during the annual Medicare re-enrollment period Oct. 15 through Dec. 7, she said. That's because ads like last year's are going to be strictly curtailed under new regulationsopens in a new tab or window in which CMS must pre-approve all television MA plan advertising. Complaints to the agency about misleading agent and advertising practices are now not only strongly encouraged, but CMS has beefed up its ability to investigate them, she said.

And there are new protections that guard against "predatory behavior to ensure that people with Medicare are not pressured into enrolling" in an MA plan, Brooks-LaSure said. For example, now, people who attend Medicare educational events cannot be subject to MA sales pitches right afterwards. Agents must also explain any impacts the change under discussion will have on a person's current coverage, something they previously weren't required to do.

She gave numerous other examples of ways CMS rules will limit marketing deception. Sellers must now disclose which plans they represent, and that they don't represent all area plans if they don't. They also can't use logos resembling Medicare, "so ads that mislead people into believing they are from the government are prohibited," Brooks-LaSure said.

The webinar was held in part to publicize a KFF reportopens in a new tab or window released Wednesday that reviewed 1,200 unique ads -- mostly for MA plans -- that aired during last year's 9-week re-enrollment window.

The KFF researchers documented that among 650,000 airings, 27% potentially misled beneficiaries into thinking they were being recruited for traditional Medicare because the ads portrayed images of a government-issued Medicare card. Some 16% urged viewers to call a "Medicare" hotline, which was a line for the plan or its agents, rather than the official 1-800 Medicare hotline, the report said.

The KFF report noted that many of last year's ads just depicted seniors looking healthy and active, such as playing tennis, mountain biking, or jumping on trampolines. "Few ads showed people with visible disabilities (4%) or the appearance of serious illness (1%) though one-fifth of Medicare beneficiaries are in fair or poor self-reported health," the report said.

Instead of conveying benefits for people with serious health conditions, many of the ads pitched offers of massage therapy or spending cards for groceries or rent, or money back in your social security checks, the report and its authors said.

"Benefits that may appeal to people in poorer health, and those that are valuable to people with serious illnesses or mobility impairments are marketed substantially less often," Jeannie Fuglesten Biniek, KFF's associate director of Medicare Policy and one of the report's authors, said during the webinar.

She said that KFF conducted focus groups and discovered many beneficiaries were confused about their coverage options, didn't know what they were trading off, and that it was difficult to compare MA plans.

The MA plan pitches featured celebrities such as Joe Namath, Lionel Richie, William Shatner, and JJ Walker, who urged seniors to "Get what you deserve!"

Webinar panelist Lindsey Copeland, director of federal policy for the non-profit Medicare Rights Center, which helps beneficiaries navigate the system, said their clients feel as if marketing materials and TV ads pressured them to sign up, even if they're perfectly happy with their current coverage. Some ads repeatedly admonished beneficiaries that they're missing out on important benefits, or implied "they're not complying with official Medicare rules or deadlines."

"Alarmingly, about 20% of our helpline calls on misleading marketing are from people who were enrolled in a plan without their knowledge or consent," Copeland said. One client just thought he was answering a caller's questions about Medicare and didn't realize he was actually being enrolled in an MA plan until he got the paperwork.

"The folks with 12 PhDs will probably find their way through these ads and find what's best for them, but not everyone will," KFF President and CEO Drew Altman said, speaking of last year's ads, some of which he described as having a "cheesiness" to them.

Webinar panelist Mark Hamelburg, representing AHIP (formerly America's Health Insurance Plans) agreed that the new CMS restrictions are important to protect beneficiaries from "bad actors," and will really change the marketing environment going forward.

But he defended MA plans in general, which now enroll 31.5 million people, saying they are "really working remarkably well," because if they weren't, "seniors would not be signing up. They would be leaving in droves." They can always go back to traditional Medicare, he said.

Copeland emphasized that MA ads need to make it clear to beneficiaries who switch that they will have network limitations, and when they need certain procedures, they will have to wait for prior authorization.

"Many were promised things that failed to materialize, you know, extra benefits, lower part B premiums, maybe robust provider networks," Copeland said. It's especially complicated for people with Original Medicare and supplemental coverage, like a Medigap, because "if you give that up, you might not be able to get it back" because most states allow supplemental plans to reject people with health issues.

"Caveat emptor is a pretty wild position to take when you're talking about older adults and people with disabilities and their health insurance," she said.

Webinar panelist Christopher Graves, president and founder of the Ogilvy Center for Behavioral Science, noted that not all of the problematic ads are selling MA plans. Rather, some are designed only to generate leads. They get the beneficiary "to pick up the phone and call and share some of your contact details. Why? They resell those contact details ... to capture your data. And it hasn't been clear to the consumers which is which."

In her remarks, Brooks-LaSure emphasized that the agency is not concerned that people are enrolling in MA plans, only that they have complete and accurate information about what they're getting when they do.

https://www.medpagetoday.com/special-reports/features/106436

Immix: 2nd Orphan Status for Candidate

 FDA Orphan Drug Designation (“ODD”) qualifies one-time treatment NXC-201 for:

  • 7 years of U.S. market exclusivity after approval

  • Tax credits for qualified clinical testing

  • Waiver of the Prescription Drug User Fee (currently at almost $3 million for a new drug)

  • The Amyloidosis market was $3.6 billion in 2017, expected to reach $6 billion in 2025, according to Grand View Research

US employers to see biggest healthcare cost jump in a decade in 2024

U.S. employers are bracing for the largest increase in health insurance costs in a decade next year, according forecasts from healthcare consultants, but workers may be somewhat spared this time around in a tight labor market.

Benefit consultants from Mercer, Aon and Willis Towers Watson see employer healthcare costs jumping 5.4% to 8.5% in 2024 due to medical inflation, soaring demand for costly weight-loss drugs and wider availability of high-priced gene therapies.

A survey conducted by Mercer, a unit of Marsh McLennan, found over two thirds of employers either do not plan to shift any cost increase to their staff or will pass on less than the expected rise in 2024.

"They don't want to add more financial stress on employees who are also coping with inflation, especially in this time where they're really relying on their health benefits as a way to keep employees working for them," said Beth Umland, Mercer's director of health & benefits research.

U.S. consumer prices accelerated 3.7% in the 12 months through August, down from a peak of 9.1% in June last year. However, medical cost increases usually lag general inflation as contracts between insurers and hospitals for the prices of procedures are signed months or even a year in advance.

Benefit consultants help design insurance plans for medium and large employers. About two-thirds of U.S. workers receive benefits through such plans.Insurers UnitedHealth, Centene, Cigna and Elevance, which manage employer insurance plans, declined to comment for this story.

Of its projected 8.5% increase in employer healthcare costs for next year, Aon anticipates 1 percentage point coming from weight-loss drugs alone.

Sales of Novo Nordisk's Wegovy, which is approved to treat obesity, as well as "off-label" use of similar diabetes drugs including Novo's Ozempic and Eli Lilly's Mounjaro for weight loss have surged in demand in the last year.

https://finance.yahoo.com/news/us-employers-see-biggest-healthcare-172328012.html

Europe to decide on Novavax's COVID vaccine in October

 The European Medicines Agency (EMA) expects to decide on the use of Novavax's updated COVID-19 vaccine in October, its director Emer Cooke said on Thursday.

The agency had started the evaluation process for the protein-based shot on Aug. 24, Cooke said at a press conference.

EU regulators recently gave the green light for an updated COVID-19 vaccine from Pfizer and its German partner BioNTech, which targets the XBB.1.5 variant of Omicron.

Moderna's updated shot is also on track to win approval.

The EMA's human medicines committee (CHMP) will discuss the shot at its meeting in October, following which the agency "should have an outcome", Cooke said.

The CHMP is scheduled to meet from Oct. 9 to 12, according to the agency's website.

Novavax said on Thursday it expects to be included in the meeting and plans to have the first doses delivered to European countries as early as October, under existing advanced purchase agreements.

The vaccine is also under review by the U.S. Food and Drug Administration.

Novavax said it was working closely with the FDA as the health regulator completes the review.

Updated mRNA-based shots from rivals Pfizer/BioNTech and Moderna have also been authorized for use in the United States.

https://news.yahoo.com/europe-expects-decide-novavaxs-covid-134809309.html

VinFast to deliver EVs to Europe this year

 VinFast could take advantage of the EU's investigation into Chinese electric vehicles.

The Vietnamese automaker plans to ship its first EVs to Europe this year after it was given regulatory approval.

A source said its VF8 crossovers would be delivered to France, Germany and the Netherlands in the fourth quarter.

The automaker's move comes at a time when Chinese EV makers face an EU probe over state subsidies.

That probe could lead to tariffs against VinFast rivals who make cars in China, and leave a gap in Europe's market.

The continent is one of the biggest markets for Chinese automakers.

Industry data shows firms like BYD and Xpeng shipped almost 70,000 EVs there in the first seven months of this year.

That's almost three times the same year-ago period.

A source told Reuters VinFast could aim to ship 3,000 VF8 SUVs to Europe this year, including some for Israel.

The model starts at just over $54,200 in France.

VinFast's expansion into Europe is part of a global plan.

The aim is to build new factories in the U.S., Indonesia and other major markets.

Though the company is currently loss-making.

First-quarter revenue dropped by just under half from the previous year, and it posted a net loss of $598 million.

https://news.yahoo.com/vinfast-deliver-evs-europe-110933316.html