Regeneron Evkeeza, with big price tag, wins FDA OK in ultra-rare cholesterol disease

 Regeneron has been battling against rival Amgen with their mass-market PCSK9 cholesterol drugs, and now the company is underway with a new launch to match its rival in the ultra-rare disease homozygous familial hypercholesterolemia (HoFH).

Regeneron’s Evkeeza scored approval on Thursday as an add-on to other lipid-lowering therapies in patients 12 and older with HoFH, which affects approximately 1,300 patients in the U.S. The company has a "dedicated and experienced team in place" to support the rollout, a spokesman said. The drug is given once per month through an intravenous infusion.

It's Regeneron's latest cholesterol drug launch after the rollout of Sanofi-partnered Praulent in 2015. Unlike Praluent, which got off to a slow start due to its high price and payer restrictions, Evkeeza targets an ultra-rare disease, likely requiring a different go-to-market strategy.

But while Praluent doesn't carry an approval in HoFH, PCSK9 rival Repatha from Amgen does. Praluent is up for an FDA decision in HoFH later this year.

Still, Evkeeza is a "first of its kind therapy and works on a completely different pathway" from PCSK9 drugs, Regeneron's spokesman said. The new drug is dosed by weight and will carry a list price of about $450,000 per year on average, Regeneron said.

Right now, though numerous therapies exist to lower LDL cholesterol, many HoFH patients can't get their levels to a healthy range, FH Foundation founder and CEO Katherine Wilemon said in an interview.

The inherited disease causes patients to produce “extraordinarily high” levels of cholesterol in the blood, which results in “very early and aggressive cardiovascular disease.” If untreated, patients often experience heart attacks in the first or second decade of their lives.  

Underdiagnosis is also an issue, and Wilemon said a new drug launch could help raise awareness about the disease. Many patients go years before reaching an accurate diagnosis, she said.

Last summer, Evkeeza snagged an FDA priority review on the heels of phase 3 data showing the medicine bested standard care.

In the trial, patients who took Evkeeza experienced LDL cholesterol reductions of 49% from baseline on average compared to placebo at week 24. Almost half of the Evkeeza patients experienced LDL-C reductions to under 100 mg/dL after entering with average levels of 260 mg/dL. Nearly all Evkeeza patients in the trial were on statins, and close to 80% were on a PCSK9 medicine, Regeneron said.  

In addition to needing several drugs, many HoFH patients and their families routinely travel for lipid apheresis treatments to cleanse the cholesterol from their blood, Wilemon said. While that's an effective treatment, it doesn't last long and cholesterol levels quickly climb back up.

Regeneron is also studying Evkeeza in refractory hypercholesterolemia and severe hypertriglyceridemia.

https://www.fiercepharma.com/pharma/regeneron-wins-fda-approval-ultra-rare-disease-hofh

SEC Suspends Trading in Inactive Issuer Touted on Social Media

 The Securities and Exchange Commission today suspended trading in an inactive company amid questions surrounding online promotion of the company’s securities and recent trading activity.

The SEC’s trading suspension order states that since late January 2021, certain social media accounts may be engaged in a coordinated attempt to artificially influence the share price of SpectraScience Inc. (OTC: SCIE), an inactive Minnesota-based corporation. The order further states that during the same period, the share price and trading volume of SpectraScience shares increased even though there was no publicly available news from the company.

The SEC’s order also states that SpectraScience is delinquent in its reporting, having not filed any periodic reports since 2017, and that its most recent website and phone number are non-functional.

On January 30, the SEC issued an alert warning investors to understand the significant risks of trading based on social media, noting that discussions on social media can tempt investors to “jump on the bandwagon,” leading to significant investment losses.

“This is a reminder that investors should exercise tremendous caution when investing based on social media or a sudden surge of enthusiasm for a particular security, especially where that interest does not appear tied to any news about the company or industry,” said Melissa Hodgman, Acting Director of the SEC’s Division of Enforcement.

Under the federal securities laws, the SEC can suspend trading in a stock for 10 days and generally prohibit a broker-dealer from soliciting investors to buy or sell the stock again until certain reporting requirements are met.

https://www.sec.gov/news/press-release/2021-28#:~:text=SEC%20Suspends%20Trading%20in%20Inactive%20Issuer%20Touted%20on%20Social%20Media,-FOR%20IMMEDIATE%20RELEASE&text=On%20January%2030%2C%20the%20SEC,leading%20to%20significant%20investment%20losses.

Drugmakers Look for New Ways to Test Covid-19 Vaccines

 As more Covid-19 vaccines become available in the U.S., it is getting tougher to run large clinical trials to test a new vaccine's ability to prevent disease because people are less willing to take a placebo -- forcing drugmakers and researchers to look for workarounds as they vet the next generation of shots and test new uses for authorized ones.

One potential workaround would be to determine what level of immune response a vaccine has to trigger to protect people from the coronavirus, as measured in blood samples, and to use that information to create smaller, faster and less-expensive clinical trials.

Instead of requiring tens of thousands of volunteers and costing several hundred-million dollars, such trials could involve only hundreds of people at a fraction of the cost. They could be used to speed the availability of new vaccines targeting emerging variants.

Moderna Inc., Pfizer and its partner BioNTech SE, and a federally funded network of researchers are conducting analyses to learn what immune response is necessary for protection with current vaccines, known as an immune correlate of protection. They say it could come in handy for new studies of already-authorized vaccines -- such as testing the shots in children or whether reduced doses are effective -- as well as for trials of the next generation of shots, including those targeting new coronavirus strains. Over time, such knowledge could also help determine how long protection from the vaccines last.

Another workaround is to run future large efficacy trials outside the U.S., in places where viral transmission is high and vaccine availability is more limited. Arcturus Therapeutics Holdings Inc., whose Covid-19 vaccine is in mid-stage testing, may run a large Phase 3 trial of its experimental shot outside the U.S. because of the diminishing feasibility of running it in the U.S., Chief Executive Joseph Payne said in an interview. The company hasn't disclosed which country or countries.

Large studies involving tens of thousands of people have been launched in the U.S. for five Covid-19 vaccines, including the two authorized for use from Moderna and Pfizer and a vaccine from Johnson & Johnson, which plans to seek U.S. authorization soon. In these studies, researchers randomly assign the volunteers to receive either the vaccine or a placebo and then compare how many get sick with Covid-19 in each group.

Vaccine vs. Placebo

But it is becoming more difficult to run these placebo-controlled efficacy trials because prospective recruits increasingly want one of the highly effective authorized shots rather than an experimental shot or a placebo, researchers say. The challenge is heightened among groups that now have access to the vaccines, like health-care workers and the elderly.

In a large study of Novavax Inc.'s vaccine, about 1.5% of the volunteers who were assigned to receive a placebo subsequently decided to get one of the authorized vaccines, Gregory Glenn, the company's head of research, said in an online scientific forum this week. More than half of those making that choice were over the age of 65.

"People in the U.S. don't want a placebo anymore if they're in a group that can get the authorized vaccines," said Dr. Kathleen Neuzil, a vaccine researcher at the University of Maryland who helps lead the federally funded Covid-19 Prevention Network, made up of research sites running large clinical trials of Covid-19 shots.

Covid-19 vaccines are designed to work by inducing a person's immune system to produce antibody proteins that can neutralize the coronavirus. The immune correlate of protection is the concentration of those antibodies at a level that prevents Covid-19 disease; antibodies below that level aren't protective, while at or above that level are protective.

The immune correlate of protection wouldn't be definitive proof that a vaccine is effective at protecting people from disease, but it could be sufficient to guide regulatory authorization of new vaccines or new uses for existing vaccines, said Peter Gilbert, a biostatistician at the Fred Hutchinson Cancer Research Center in Seattle and part of the Covid-19 Prevention Network. Regulators would still require reports of any side effects to determine safety and might require further studies to confirm efficacy.

A Predictive Blueprint

Such correlates of protection have been used for past vaccine development. The Food and Drug Administration has approved certain meningitis vaccines based on their ability to induce an immune response that correlates with protection, rather than requiring large placebo-controlled efficacy trials.

"It saves time, it saves money and it may be the only thing that's logistically feasible going forward," Dr. Neuzil said.

Covid-19 vaccines researchers expect to determine the immune correlate of protection by comparing antibody levels in blood samples taken from vaccinated people who stayed healthy with antibody levels in the relatively small number of vaccinated people in the studies who still got sick from Covid-19.

Researchers from the Covid-19 Prevention Network are running analyses to try to determine the immune correlate of protection for Moderna's vaccine within the next couple of months. They are examining some of the blood samples taken from all subjects about one month after the second dose in the large clinical study of the Moderna vaccine.

They plan to conduct similar analyses for other Covid-19 vaccines from J&J, AstraZeneca PLC and Novavax, which are being tested in trials run by the researchers' network.

Pfizer and BioNTech are conducting their own analysis to determine the correlate of protection for their Covid-19 vaccine. A Pfizer spokeswoman said the company would explore the use of immune responses in additional studies of its vaccine, such as in pregnant women, children and people with compromised immune systems.

Leaders of the Covid-19 Prevention Network expect that future vaccines could be approved based on trials of only several hundred people, if results show that they had an immune response believed to be protective.

Moderna is exploring the use of an immune correlate of protection to test whether a half-dose of its vaccine could offer sufficient protection against Covid-19 disease, Chief Medical Officer Tal Zaks said at a recent investor conference.

Expanding Vaccine Uses

An FDA spokeswoman said that when immune correlates of protection are established for these vaccines, they will be useful for a variety of studies including the evaluation of vaccines in children and assessing the response to new variants.

There are challenges for determining protective immune responses. There were relatively few cases of symptomatic Covid-19 in people who received the Moderna and Pfizer vaccines in the large studies at the time they were authorized, making statistically significant comparisons difficult. But researchers continue to follow study subjects and expect to see higher numbers.

https://www.marketscreener.com/quote/stock/MODERNA-INC-47437573/news/Drugmakers-Look-for-New-Ways-to-Test-Covid-19-Vaccines-32420081/

Molecular Templates in Cancer Collaboration With Bristol Myers

 Molecular Templates Inc. on Thursday said it signed a cancer collaboration agreement potentially worth more than $1.3 billion with drug giant Bristol Myers Squibb Co.

Molecular said the collaboration will use its engineered toxin body, or ETB, platform to discover and develop multiple novel therapies aimed at specific oncology targets.

The Austin, Texas, clinical-stage biopharmaceutical company said it will receive an up-front payment of $70 million from Bristol Myers, adding that is eligible for up to roughly $1.3 billion in milestone payments, along with royalties on sales.

Molecular said it will conduct research activities for the discovery of ETBs for multiple targets, the first of which Bristol has already selected. New York-based Bristol will have the option for exclusive worldwide licenses for the ETBs and will be responsible for their development and commercialization, Molecular added.

Shares of Molecular, which closed Wednesday at $12.82, rose more than 25% in premarket trading Thursday.

https://www.marketscreener.com/quote/stock/MOLECULAR-TEMPLATES-INC-37318006/news/Molecular-Templates-in-Cancer-Collaboration-With-Bristol-Myers-32419338/

Second COVID Shot Packs the Big Punch

 Like scores of other physicians and healthcare workers, T.J. Maltese, DO, a neurologist in private practice on Long Island in New York state, had no problem with his first dose of the Moderna coronavirus vaccine -- but he was knocked out by the second.

Maltese got his second shot at 4:30 p.m. on a Friday. Within 2 hours his arm was sore. He developed flu-like symptoms overnight, and had chills and body aches on Saturday. His low-grade fever (peaking at 101.4°F) lingered all day. If he had to work, he could have pushed through, he said, but he rode out his symptoms on his couch with the help of the occasional Tylenol.

By 9 p.m. Saturday, Maltese started to feel better. He got a good night's sleep and was back to normal on Sunday.

"I know plenty of people with minimal symptoms after the second dose, so it's not definite you'll feel side effects," he wrote in a Facebook post. "But be prepared for the possibility."

The healthcare worker scuttlebutt is that the second dose of any COVID-19 vaccine packs a punch -- unless you've already had COVID, then the first dose can hit just as hard.

These perceptions are substantiated by immunology and by data from the vaccines' phase III trials, and some hospitals have even altered their healthcare worker scheduling in anticipation of second-dose side effects.

Priming the Immune System

Immunologists and infectious disease experts interviewed by MedPage Today said it's not unexpected that second-dose reactions are more intense than the first.

"The first time the immune system comes into contact with something, it's getting primed," said Purvi Parikh, MD, an immunologist at NYU Langone Health in New York City. "That goes for everything, from vaccines to allergies. It's rare on the first time to have a strong reaction. After that, the immune system recognizes it, so you have a much stronger reaction."

"We saw it in the trials, so it's really not surprising," Parikh added. "Now we're seeing it in real time as the vaccines are being rolled out."

In both Pfizer's and Moderna's phase III trial data, systemic adverse events were reported more frequently after dose 2 than dose 1. For the latter, rates were 54.9% versus 42.2% for placebo after the first dose and 79.4% versus 36.5% for placebo after the second dose. Fever, headache, fatigue, myalgia, arthralgia, and chills were far more common after the second dose compared with the first dose and with all placebo doses.

Stanley Weiss, MD, an infectious disease specialist and epidemiologist at Rutgers New Jersey Medical School, said since his institution served as a site for the Moderna trial, the primary investigator was able to give faculty and administrators an early update on what to expect following vaccination.

"They said there was a very high rate of fatigue after the second dose, so we encouraged administrators ... to figure that many healthcare workers getting the vaccine might not be well enough to work the day after the second dose," Weiss told MedPage Today.

Weiss added that administrators were also careful not to vaccinate staff from within the same unit -- an ICU team, for instance -- on the same day.

Fewer Problems for Older Patients?

Both Weiss and Parikh said they had a far stronger response to the second dose of the Moderna and Pfizer vaccines, respectively. Weiss had fatigue and a severe headache for 2 days. Parikh's chills, fatigue, and headache resolved within 24 to 36 hours.

Zubin Damania, MD, a.k.a. ZDoggMD, said the second dose of his Moderna vaccine knocked him out: "I couldn't sleep, I had a fever, rigors, body aches, a headache -- full-on man-flu," he joked on a recent episode of his show.

His guest for that show was vaccine expert Paul Offit, MD, who also had fever and fatigue for about 48 hours after the second dose of the Pfizer vaccine.

"That reaction is less common in people over 65, and I'm over 65, so I'm thinking I'm not going to suffer that, but I did," Offit said.

Indeed, older patients are thought to have less of a reaction due to typical weakening of the immune system as people age, Parikh said: "The idea is that their immune system is not as robust as a young person's."

Dose 1 Rougher for Those with Previous COVID

Parikh said the same immunological concept behind a stronger response to the second dose also applies to first-dose effects for those who've had COVID-19 before.

"It's the same reason why some people who've had COVID and recovered get these effects with the first shot sometimes. The immune system has seen it before," she said.

Victoria Arthur, MD, of Lexington Pediatrics in Massachusetts, suspects she had COVID in March 2020, but wasn't able to confirm her diagnosis. Still, while all of the other physicians and healthcare staff in her office felt fine after the first dose of the Moderna vaccine, she did not.

"How I felt was how everyone else was describing their second vaccine," Arthur told MedPage Today.

Within three hours of her first dose, she had a headache, neck pain, and cognitive fog. She woke up at 3 a.m. with bad nausea and stomach cramps, and spent the entire next day in bed. By Monday, though, her only lingering symptom was a sore arm.

Her reaction to her second dose was similar, she said. Nonetheless, she was glad for it.

"I'm always grateful when I have a reaction, that means the body is doing its thing," she said. "I'm very fortunate to have been given the vaccine, so any side effect is worth it."

Being appreciative of having been vaccinated, despite the side effects, was a common sentiment among these healthcare professionals.

Weiss said second-dose side effects shouldn't deter anyone from getting vaccinated: "The benefits greatly overwhelm the risk of side effects. It's not a reason to delay."

"I'll take 30 hours of some mild misery," Maltese said, "over days to weeks of much worse -- and more unpredictable -- misery."

https://www.medpagetoday.com/special-reports/exclusives/91157

Inpixon to Provide CO2 Sensors to Help Identify COVID-19 Infection Risk

 Inpixon Partners with Unitronic to Distribute CO2 Sensor Modules for Indoor Air Quality Measurement

Research Supports Using Carbon Dioxide as a Proxy of SARS-CoV-2 Concentrations Indoors

PALO ALTO, Calif. and BERLIN, Feb. 11, 2021 /PRNewswire/ -- Inpixon (Nasdaq: INPX), the Indoor Intelligence™ company, today announced the distribution by Unitronic of Inpixon's carbon dioxide (CO2) sensor modules for use to measure indoor air quality, an important indicator of SARS-CoV-2 and other pathogen transmission risk. Unitronic is a leading European distributor and integrator of sensors, communication equipment, and other electronics, and it is a member of Lagercrantz Group AB which operates more than fifty companies and has activities in Europe, India, China and the U.S.

Under the agreement, Unitronic plans to sell Inpixon's CO2 sensor modules as well as additional Inpixon products to its existing base of OEMs, system integrators and solution providers. The integrator-ready modules include a modern, low power, non-dispersive infrared (NDIR) sensor which features automatic calibration and provides a range of gas readings, rather than simply above- or below-threshold readings. Unitronic anticipates the Inpixon sensors will be included in environment control units, building automation systems, and ventilation-on-demand solutions that can help ensure a clean air supply within commercial and public buildings.

Public health advice has been slow to catch up with the rapidly advancing science showing that COVID-19 is mainly spreading in enclosed spaces whenever people spend extended periods breathing tiny aerosol droplets suspended in air infected by the virus, according to Martin Z. Bazant, Ph.D at Massachusetts Institute of Technology. Research by Professors Zhe Peng and Jose L Jimenez at the University of Colorado Boulder states that CO2 is co-exhaled with aerosols containing SARS-CoV-2 by COVID-19 infected people and as such, CO2 can be used as a proxy of SARS-CoV-2 concentrations indoors. Indoor CO2 measurements through the use of sensors holds promise for mass monitoring of indoor aerosol transmission risk for COVID-19 and other respiratory diseases.

https://finance.yahoo.com/news/inpixon-co2-sensors-help-identify-143000039.html

Cuomo is shamefully fumbling nursing-home vaccinations

 Gov. Andrew Cuomo’s Department of Health has once again put the needs of nursing-home residents last.

Just as the department under Commissioner Howard Zucker neglected to make sure that the homes had testing and personal protective equipment during the deadly early months of the pandemic, now it is turning away vulnerable New Yorkers from the third and final federal vaccination clinics that are taking place in these facilities.

Worse, the DOH still hasn’t made any clear-cut plans to continue vaccinating nursing-home residents once the federal program is over.

A bit of recent history is in order: The department shelved its plan for vaccinating nursing-home residents back in December, electing instead to participate in the Federal Pharmacy Partnership for Long-Term Care. Part of Operation Warp Speed, the FPP program was designed to rapidly vaccinate all of the nation’s long-term-care residents at no cost to the residents or the facilities.

The feds contracted with CVS, Walgreens and other pharmacy providers to administer the two required vaccine doses to all residents over the course of three clinic sessions scheduled three weeks apart; the federal program ends after the third session, after which the states are supposed to carry the ball.

Like the rest of Operation Warp Speed, the FPP has proved an astonishing success; shots started going into the arms of nursing-home residents within days of the Pfizer vaccine receiving Food and Drug Administration authorization for emergency use in December.

Executing a well-designed offensive strategy, FPP professionals arrived at the homes right on schedule, equipped with the exact number of thawed-out vaccines, syringes and needles to inoculate everyone in the facility. Three weeks later, they were back for Session No. 2, giving the second shot to those who had received the first one and the first to anyone who had been newly admitted in the interval.

Now the feds are executing their final play, finishing up giving the second shots before they leave the game for good.

Unfortunately, just as it didn’t prepare for the vaccine rollout to the state’s general population, the Cuomo administration is now scrambling to figure out how to vaccinate nursing-home residents once the federal program ends.

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Even worse, in yet another shocking example of disregard for this population, the department isn’t allowing new residents to get the first dose of the vaccine during the third FPP session. But why? How can this be? COVID-19 outbreaks and deaths are still occurring in these facilities in significant numbers, even though you never hear about them during the governor’s regular news conferences.

Instead, when he isn’t patting himself on the back, Cuomo subjects us to endless gushing over the Biden administration’s federalized approach to COVID-19 vaccinations. Well, if he is so enamored of this, why is he ignoring the Centers for Disease Control and Prevention’s explicit recommendation that first shots be given at the final FPP clinic?

Every day that passes is another missed opportunity to vaccinate new nursing-home residents as the FPP teams prepare to finish their work.

This should never have been allowed to happen. From the time it was announced in October, it’s been well known that the federal program would cease to exist after the third session. The state had months to design a plan to vaccinate future residents. But as we are so tragically aware, nursing homes have never been a priority for this administration.

The Department of Health must immediately announce that newly admitted nursing-home residents should get their first vaccine shots at the final FPP clinics; it can figure out later how to make sure that the second shots are given.

The CDC has indicated that it is safe to wait as long six weeks between shots, if need be, so there is still plenty time on the clock. CVS, Walgreens and other FPP participants must be given the signal to stay in the game for now until the nursing homes’ usual pharmacy vendors or other suppliers can step in.

Whatever happens, we mustn’t leave our nursing-home residents defenseless again.

Elaine Healy, MD, is a practicing geriatrician, nursing-home medical director and member of the Infection Control Subcommittee of the Society for Post-Acute and Long-Term Care Medicine.

https://nypost.com/2021/02/10/cuomo-is-shamefully-fumbling-nursing-home-vaccinations/