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Monday, November 6, 2023

Apellis parries Astellas' long-term Izervay data with 3-year results on rival GA med Syfovre

 After this summer’s FDA approval of Iveric Bio’s Izervay—the drug at the center of the $5.9 billion buyout by Japanese pharma Astellas—the battle for the geographic atrophy (GA) crown is on in the U.S. Now, Apellis Pharmaceuticals, which boasts embedded eye disease sales leader Syfovre, is putting up long-term data in a bid to outdo its new rival. 

Touting data from its GALE extension study, Apellis on Saturday said Syfovre yielded increasing treatment effects year over year and helped patients achieve more than a 40% reduction in non-subfoveal lesion growth at the study’s three-year mark. 

Apellis rolled out the latest GALE results as part of a presentation at this year’s meeting of the American Academy of Ophthalmology (AAO) in San Francisco. The timing coincides with the release of two-year data on Astellas and Iveric’s GA drug Izervay—also at AAO—which suggest the rival drug’s treatment benefit emerged in as few as six months, with the effect growing over time.

Izervay bagged FDA clearance in early August, less than four months after Astellas acquired the drug’s developer Iveric. Apellis’ Syfovre became the first drug approved for GA back in February.

Syfovre previously carried peak sales expectations of $3 billion, though the edge conferred by its early approval waned with reports of rare but serious side effects. More recently, however, Apellis’ drug has shown signs of recovery.

Aside from the reduction in non-subfoveal lesion growth—or the growth of lesions in the outer retina—Apellis’ three-year results showed that Syfovre reduced general GA lesion growth by 35% and 24% when given monthly or every other month, respectively, versus placebo.

Syfovre’s safety profile was on par with previously reported data, the company added. The company flagged one serious case of ischemic optic neuropathy in the monthly cohort, which the company previously reported. Intraocular inflammation cropped up at a rate of 0.26% per injection from months zero to 36, which excluded four cases linked to an impurity snafu from 2018.

Apellis pointed out that no cases of retinal vasculitis have been observed in its clinical studies of Syfovre, in which more than 24,000 injections have been administered.

Reports of Syfovre causing occlusive retinal vasculitis—a type of eye inflammation that can potentially cause blindness—surfaced in July after the American Society of Retinal Specialists flagged instances of the rare but serious side effect in a letter to doctors.

At the time, an Apellis spokesperson told Fierce Pharma the drug’s overall real-world safety profile had been “consistent” with its clinical trials.

In August, Apellis said problems with a filter needle included in certain Syfovre injection kits could be behind the side effect streak.

The company stopped short of declaring a causal relationship but recommended healthcare providers immediately stop using injection kits containing the specific filter needle.

As of early October, Apellis had reported 10 confirmed retinal vasculitis events, which worked out to a 0.012% chance per injection, according to analysts with Evercore ISI.

Despite the side effect issue, recent shipping patterns suggest “doctors do appear to be moving on from the vasculitis scare in July,” the analysts wrote in a note to clients last month.

Meanwhile, Astellas is busy making the case for long-term use of Izervay. At AAO, investigators shared two-year results from the GATHER2 study, which tested the drug every month or every other month against placebo in GA patients.

In Year 2 of the study, Izervay met its primary objective by delivering a statistically significant year-over-year reduction of 14% in the mean rate of GA lesion growth. When given every other month in Year 2 after monthly dosing during Year 1, Izervay yielded a 19% reduction in the mean rate of GA lesion growth.

That said, the Astellas drug failed a prespecified objective looking at its ability to reduce vision loss.

https://www.fiercepharma.com/pharma/apellis-parries-astellas-long-term-izervay-data-3-year-results-its-rival-geographic-atrophy

Gal Gadot Plans Screening of IDF Footage Showing Hamas Atrocities

 "Wonder Woman" star Gal Gadot plans to screen footage provided by the Israel Defense Forces (IDF) showing the brutal acts of Hamas terrorists committed during the Oct. 7 invasion of Israel.

Israel's 124 news outlet announced a Hollywood screening of the 47-minute footage for a select audience of celebrities and influential personalities.

Oscar-winning director Guy Nattiv, who spearheaded the initiative, confirmed to 124 that Gadot and her husband, Yaron Varsano, "helped make this possible."

"As a filmmaker, I swore that these images of October 7 would not be forgotten, and the world would see them," he added. "Because now the denial begins - it is a fake, it is not a fake (…) We cannot pass by in silence."

Nattiv highlighted the broad spectrum of viewers attending the screening.

"People who have film experience, so we can show them this crazy document that is reminiscent of the films created about the Holocaust."

The initial plan is to host a single screening for 120 viewers, with potential additional screenings based on its reception.

The video content is said to be deeply disturbing and has already been watched by numerous foreign journalists and Israeli Knesset members.

The footage will be showcased under the title "Bearing Witness to the October 7th Massacre" in Los Angeles and New York this week, according to The Wrap, which noted that one of the screenings will take place by invite only Wednesday at the Museum of Tolerance.

According to reports, the footage, which was mostly filmed by Hamas terrorists, includes murder, mass rapes and beheadings of Jewish people as well as the massacre at the Nova music festival. The American Jewish Committee and the Anti-Defamation League are helping to organize the screenings.

Nattiv shared a redacted image of the invitation on social media Sunday, captioning the post "Because the world needs to know. #neveragainisnow"

https://www.newsmax.com/thewire/gal-gadot-idf-footage/2023/11/06/id/1141147/

Medicaid Disenrollments Pass 10 Million As States Continue Eligibility Checks

 By Rebecca Pifer of HealthcareDive

Summary

  • More than 10 million low-income Americans have lost Medicaid coverage as states continue checking eligibility for the safety-net program following the pandemic.

  • The U.S. passed that marker as of Nov. 1, according to a tracker by health policy nonprofit KFF, which started collecting data on Medicaid enrollment in April when states could begin redeterminations.

  • To date, 35% of the 28 million people with a completed renewal were disenrolled, while 65% had their coverage renewed. Disenrollments vary widely by state — Texas has the highest disenrollment rate at 65%, while Illinois has the lowest at 10%, KFF found.

Disenrollment rates have been rising steadily since this summer, as more states start rechecking their Medicaid members’ eligibility for the program.

The Biden administration enticed states to put those checks on hold during the COVID-19 public health emergency in exchange for more generous federal funding. That continuous enrollment period caused Medicaid’s rolls to swell to some 94 million people earlier this year, making the program the largest source of insurance coverage in the U.S. during the pandemic.

Millions of people were expected to lose coverage at the end of Medicaid unwinding, though the actual number is currently very much in flux. Patient advocates, Democrat lawmakers and health policy researchers have raised concerns about redeterminations, as high numbers of people have lost coverage for administrative errors, not actual ineligibility. In addition, states’ different strategies are complicating efforts to get a clear national picture of how redeterminations are playing out.

Disenrollment figures are almost certainly an undercount, due to data lags, KFF noted.

But across states with available data, 71% of all people disenrolled lost coverage for procedural reasons like not filling out paperwork by the deadline, or the state being unable to contact them. That’s a small dip from earlier this year, when the KFF found 74% of terminations were procedural.

The Biden administration has taken a number of steps in an effort to curb procedural disenrollments, including offering states more flexibility in how they pursue redeterminations. To date, all states have taken the CMS up on the additional assistance, except Florida.

Regulators have also threatened state agencies with sanctions over an administrative glitch that improperly removed children from Medicaid coverage, and forced states with high levels of procedural terminations to pause redeterminations.

Those actions are resulting in more Medicaid members rejoining the program after being kicked off, according to health insurance executives.

In recent third-quarter earnings calls, CenteneMolina and Elevance — all of which contract with states to manage the care of their Medicaid beneficiaries — said they’re seeing the rate of reconnects accelerate as compared to earlier this year.

In addition, states are revising rates to reflect changing acuity as payer’s membership rolls change, which should insulate insurers from extreme unexpected medical costs.

Despite that, however, redeterminations continue to stress payers’ financial outlooks. Earlier this year, Centene lowered its 2024 earnings guidance due to expectations that Medicaid redeterminations will increase spending and lower premium revenue next year. And Molina in October lowered its member retention expectations after redeterminations are completed, from 50% to 40%.

https://www.zerohedge.com/markets/medicaid-disenrollments-pass-10-million-states-continue-eligibility-checks

Home Depot Founder Calls Biden A "Dunce," Says President Is A "Puppet"

 Home Depot co-founder Bernie Marcus, who has railed against "socialism," corporate "wokeness," and the Biden administration, recently spoke with FOX Business Charles Gasparino about why he is in a "particularly pissed-off mood" these days. 

"I've said this to all of my friends, anybody who would listen: if this election goes the way the last one went, this country will be a Third World country," the 94-year-old billionaire told Gasparino. 

Marcus blames the social and economic mess consuming the country on President Biden, calling the president a "dunce" and saying he's the "most divisive president we've ever seen." Labeling half the country as a 'MAGA Republican' was never a way to promote 'unity,' he continued. 

The billionaire then talks about Biden's deteriorating mental state, saying, "Somebody is feeding him like a puppet." He warned against the massive spending increase and numerous policy errors that triggered high inflation and an explosion in debt. 

Marcus acknowledges some positives during the Trump administration, such as increased wages, higher employment among minorities, and low inflation. However, he expresses concerns about Trump's personality, particularly his inability to "keep his mouth shut . . . I'm afraid if he's elected, the first thing he does is go after his enemies, starting with the Republicans." 

Marcus said, "I think [Trump] has the policies if he would just follow the script and do what he has to do."

Gasparino asks the billionaire if he could build another Home Depot in today's environment. The short answer is 'no': "Regulations and all this woke crap" have made starting a public company near impossible, he said. 

He added: "I ran a business for 60 years... I would never get involved with a social issue outside of business. That was not my business."

Marcus said there was some hope for the future of the company as Americans were quickly turning on radical leftists. The example he gave was the Bud Light boycott:

"They were No. 1 . . . and they turned stupid overnight," he said. "The American people remember; their sales are going to stay down."

He concludes by saying the American people are worth saving from what he believes is a progressive apocalypse... 

In a separate interview earlier this year, Marcus told Americans to "wake up" to the reality that the economy is in "tough times" following the collapse of Silicon Valley Bank. 

Months before that, in December 2022, he railed against "socialism" for why nobody wants to work and warned capitalism is in dire straits. 

Marcus' warning is similar to co-founder and retired CEO of Whole Foods, John Mackey, who recently warned that "socialists are taking over" and 'capitalism cannot be replaced with disastrous socialism.' 

The positive takeaway is that the Bud Light boycott serves as a barometer of American sentiment, indicating widespread discontent with progressive policies across the corporate world to local, state, and federal governments.

https://www.zerohedge.com/political/home-depot-founder-calls-biden-dunce-says-president-puppet

Krystal's topical gene therapy gains steam, prompting analyst group to boost sales projection

At the start of its first-ever conference call to present its quarterly numbers, Krystal Biotech CEO Krish Krishnan was quick to point out that the company’s positive earnings for the third quarter can be attributed to its recent sale of an FDA priority review voucher (PRV) for $100 million.

It shouldn’t be long before the eight-year-old Pittsburgh biotech can chalk its positive earnings up to drug sales, however, after launching Vyjuvek, the world’s first-ever topical gene therapy. The drug was approved by the FDA in May to treat certain patients with dystrophic epidermolysis bullosa (DEB).

While the Wall Street consensus projects Vyjuvek’s sales will come in at $163 million next year, Evercore ISI has boosted its own estimate to $273 million based on launch metrics the company provided Monday.

“We expect revenue to come in very strong over the next six months, driving Krystal to reach GAAP profitability by the middle of next year,” Evercore ISI analysts Gavin Clark-Gartner and Yesha Patel wrote in a note to clients.

In its third-quarter update, the company said it finished the quarter with 284 start forms for the treatment, with demand continuing to be strong. Krystal projects an 85% conversion rate in turning those requests into prescriptions.

A third of the start forms are for patients between the ages of six months and 10 years, who typically have a longer induction phase, leading to potentially more consumption of Vyjuvek, the company said.

One advantage favoring strong uptake is that Vyjuvek can be taken at home. Of the patient start forms received, 88% were for those who wanted to take the drug at home. Though it’s very early, that has helped drive a 96% rate of adherence, according to the company.

“We believe we have a strong launch in our hands,” Krishnan said during the call. “We see really good demand from both recessive and dominant patients, access coverage has been relatively smooth, and home health visits are pointing to a high patient compliance. We expect this momentum to continue going forward.”

Krystal reported revenue of $8.6 million in the third quarter for Vyjuvek, with the company adding that the figure accounts for less than two months of sales because the first commercial patient did not receive treatment until early August.

Last month, Krystal filed for approval of Vyjuvek in Europe, with the company anticipating approval there in the second half of 2024, it said. The company has kicked off an open label extension study of the drug in Japan and expects to file for approval there in early 2024.

Krystal sold its PRV to an undisclosed company in August. It was obtained when the FDA signed off on Vyjuvek under the Rare Pediatric Disease Priority Review Voucher Program.

DEB is a genetic condition that causes blisters that can lead—in its most severe form—to vision loss and disfigurement. Those with DEB lack a gene that adheres the inner and outer layers of the skin, leaving it vulnerable to even the slightest friction. After application of the topical gel to wounds, Vyjuvek helps bind the layers together.

https://www.fiercepharma.com/pharma/krystals-successful-launch-topical-gene-therapy-kyjuvek-prompts-projected-sales-boost-273m

Paxlovid Ineffective at Reducing Most Post-COVID Conditions

 Nirmatrelvir-ritonavir doesn't reduce the incidence of most post-COVID conditions, according to a new study. Thromboembolic events are the exception.

METHODOLOGY:

  • A retrospective study of 9593 veterans older than 65 years examined the impact of nirmatrelvir-ritonavir in comparison with no treatment on post-COVID-19 conditions (PCCs).

  • Researchers coded 31 conditions, including those that fell into cardiac, pulmonary, renal, thromboembolic, gastrointestinal, neurologic, mental health, musculoskeletal, and endocrine categories.

  • The incidence of PCCs was analyzed 31 to 180 days after treatment.

TAKEAWAY:

  • The combined incidence of venous thromboembolism and pulmonary embolism was reduced among patients given nirmatrelvir-ritonavir.

  • No statistically significant reduction of other conditions was found.

  • Results differ from the conclusions of a smaller study that found that the incidence of 10 of 13 PCCs was lower.

IN PRACTICE:

"Our results suggest that considerations about PCCs may not be an important factor in COVID-19 treatment decisions," the authors write.

SOURCE:

The study was funded by the US Department of Veterans Affairs and was published online in Annals of Internal Medicine on October 30. George Ioannou, MD, director of hepatology at the VA Puget Sound Health Care System in Seattle, led the study.

LIMITATIONS:

A large number of outcomes were observed, so it's possible that the association between treatment with nirmatrelvir-ritonavir and reduced incidence of thromboembolic events occurred by chance.

Data on COVID-19 treatments and PCCs may be incomplete. The long-term effects of PCCs may not have been fully captured by the International Classification of Diseases, 10th Revision, which was used for diagnosis codes.

Electronic health records did not accurately capture the symptom burden or the date symptoms began. Patients in the treatment arm may have had more symptoms than matched control persons who were not treated.

DISCLOSURES:

The authors reported relationships with the Korean Diabetes Association, the American Diabetes Association, the International Society for the Diabetic Foot, Quality Insights, Brown University, and the Society for Women in Urology, among others.

https://www.medscape.com/viewarticle/997878

How to Prescribe Exercise in 5 Steps

 Clinicians are well aware of the benefits of physical activity — and the consequences of inactivity. 

Managing the diseases associated with inactivity — heart disease, type 2 diabeteshypertension — falls to physicians. So one might assume they routinely prescribe exercise to their patients, just as they would statins, insulin, or beta-blockers. 

But evidence indicates doctors don't routinely have those conversations. They may lack confidence in their ability to give effective advice, fear offending patients, or simply not know what to say.

That's understandable. Many doctors receive little training on how to counsel patients to exercise, according to research over the past decade. Despite efforts to improve this, many medical students still feel unprepared to prescribe physical activity to patients.

But here's the thing: Doctors are in a unique position to change things.

Only 28% of Americans meet physical activity guidelines, according to the Centers for Disease Control and Prevention. At the same time, other research suggests that patients want to be more active and would like help from their doctor.

"The value comes in having a physician emphasize the importance [of exercise]," says Dr Jane Thornton. The more time you spend on it, the more that value comes through.

"Patients are motivated to hear about physical activity from physicians and try to make a change," says Jane Thornton, MD, PhD, an assistant professor in family medicine at Western University in Ontario, Canada. "Just saying something, even if you don't have specialized knowledge, makes a difference because of the credibility we have as physicians."

Conveniently, just like exercise, the best way to get started is to…get started.

Here's how to break down the process into steps.

1. Ask patients about their physical activity.

Think of this as taking any kind of patient history, only for physical activity.

Do they have a regular exercise routine? For how many minutes a day are they active? How many days a week?

"It takes less than a minute to ask and record," Thornton says. Once you put it into the patient's electronic record, you have something you can track.

2. Write an actual prescription .

By giving the patient a written, printed prescription when they leave your office, "you're showing it's an important part of treatment or prevention," Thornton explains. It puts physical activity on the level of a vital sign.

Include frequency, intensity, time, and type of exercise. The American College of Sports Medicine's Exercise is Medicine initiative provides a prescription template you can use.

3. Measure what they do.

Measurement helps the patient adopt the new behavior, and it helps the physician provide tailored advice going forward, Thornton says.

With the rise of health-monitoring wearables, tracking activity has never been easier. Of course, not everyone wants to (or can afford to) use a smartwatch or fitness tracker.

For tech-averse patients, ask if they're willing to write something down, like how many minutes they spent walking, or how many yoga classes they attended. You may never get this from some patients, but it never hurts to ask.

4. Refer out when necessary.

This brings us to a sticky issue for many physicians: lack of confidence in their ability to speak authoritatively about physical activity. "In most cases, you can absolutely say, 'Start slow, go gradually,' that kind of thing," Thornton says. "As with anything, confidence will come with practice."

For specific prescriptive advice, check out the Exercise is Medicine website, which also has handouts you can share with patients and information for specific conditions. If your patient has prediabetes, you can also point them toward the CDC's diabetes prevention program, which is available in-person or online and may be free or covered by insurance.

If a patient has contraindications, refer out. If you don't have exercise or rehab professionals in your network, Thornton recommends reaching out to your regional or national association of sports-medicine professionals. You should be able to find it with a quick Google search. 

5. Follow up.

Ask about physical activity during every contact, either in person or online. 

Thornton says the second and fifth steps matter most to patients, especially when the prescription and follow-up come from their primary care physician, rather than a nurse or physician assistant to whom you've delegated the task.

"The value comes in having a physician emphasize the importance," Thornton says. The more time you spend on it, the more that value comes through.

What NOT to Say to Patients About Exercise

This might surprise you: 

"I definitely don't think telling people the official recommendations for physical activity is useful," says Yoni Freedhoff, MD, an associate professor of family medicine at the University of Ottawa and medical director of the Bariatric Medical Institute. "If anything, I'd venture it's counterproductive."

It's not that there's anything wrong with the recommended minimum — 150 minutes of moderate-to-vigorous-intensity physical activity per week. The problem is what it says to a patient who doesn't come close to those standards. 

"Few real-world people have the interest, time, energy, or privilege to achieve them," Freedhoff says. "Many will recognize that instantly and consequently feel less than that is pointless."

And that, Thornton says, is categorically not true. "Even minimal physical activity, in some cases, is beneficial."

You also want to avoid any explicit connection between exercise and weight loss, Thornton says.

Though many people do connect the two, the link is often negative, notes a 2019 study from the University of Toronto, triggering painful memories that might go all the way back to gym class. 

Try this pivot from Freedhoff: "Focus on the role of exercise in mitigating the risks of weight," he says — like decreasing pain, increasing energy, and improving sleep.

How to Motivate Patients to Move

New research backs up this more positive approach. In a study published today in Annals of Internal Medicine, doctors in the UK who emphasized benefits and minimized health harms convinced more patients to join a weight management program than negative or neutral docs did. These doctors conveyed optimism and excitement, smiling and avoiding any mention of obesity or body mass index.

Exactly what benefits inspire change will be different for each patient. But in general, the more immediate the benefit, the more motivating it will be. 

As the University of Toronto study noted, patients weren't motivated by vague, distant goals like "increasing life expectancy or avoiding health problems many years in the future."

They're much more likely to take action to avoid surgery, reduce medications, or minimize the risk of falling. 

For an older patient, Freedhoff says, "focusing on the preservation of functional independence can be extremely motivating." That's especially true if the patient has vivid memories of seeing a sedentary loved one decline late in life. 

For patients who may be more focused on appearance, they could respond to the idea of improving their body composition. For that, "we talk about the quality of weight loss," says Spencer Nadolsky, DO, an obesity and lipid specialist and medical director of WeightWatchers. "Ultimately, exercise helps shape the body instead of just changing the number on the scale."

Reducing Resistance to Resistance Training

A conversation about reshaping the body or avoiding age-related disabilities leads naturally to resistance training.  

"I always frame resistance training as the single most valuable thing a person might do to try to preserve their functional independence," Freedhoff says. If the patient is over 65, he won't wait for them to show an interest. "I'll absolutely bring it up with them directly."

Freedhoff has an on-site training facility where trainers show patients how to work out at home with minimal equipment, like dumbbells and resistance bands. 

Most doctors, however, don't have those options. That can lead to a tricky conversation. Participants in the University of Toronto study told the authors they disliked the gym, finding it "boring, intimidating, or discouraging." 

And yet, "a common suggestion…from healthcare providers was to join a gym."

Many patients, Nadolsky says, associate strength training with "grunting, groaning, or getting 'bulky' vs. 'toned.' " Memories of soreness from overzealous workouts are another barrier.

He recommends "starting small and slow," with one or two full-body workouts a week. Those initial workouts might include just one to two sets of four to five exercises. "Consider if someone is exercising at home or in a gym to build a routine around equipment that's available to them," Nadolsky says.

Once you determine what you have to work with, help the patient choose exercises that fit their needs, goals, preferences, limitations, and prior injuries.

One more consideration: While Nadolsky tries to "stay away from telling a patient they need to do specific types of exercise to be successful," he makes an exception for patients who're taking a GLP-1 agonist. "There is a concern for muscle mass loss along with fat loss."

Practicing, Preaching, and Checking Privilege

When Thornton, Freedhoff, and Nadolsky discuss exercise, their patients know they practice what they preach. 

Nadolsky, who was a nationally ranked wrestler at the University of North Carolina, hosts the Docs Who Lift podcast with his brother, Karl Nadolsky, MD. 

Freedhoff is also a lifter and fitness enthusiast. 

And Thornton was a world-class rower whose team came within 0.8 seconds of a silver medal at the Beijing Olympics. (They finished fourth.)

But not all physicians follow their own lifestyle advice, Freedhoff says. That doesn't make them bad doctors — it makes them human.

"I've done 300 minutes a week of exercise" — the recommended amount for weight maintenance — "to see what's involved," Freedhoff says. "That's far, far, far from a trivial amount." 

That leads to this advice for his fellow physicians:

"The most important thing to know about exercise is that finding the time and having the health to do so is a privilege," he says. 

Understanding that is crucial for assessing your patient's needs and providing the right help.

https://www.medscape.com/viewarticle/998141