FDA to allow sale of COVID tests without studying efficacy in asymptomatic people

 The FDA said March 16 it will allow manufacturers of COVID-19 tests to market tests for at-home or point-of-care use without studying how well they work in asymptomatic people. 

The agency said its goal is to make it easier to screen people returning to work and school. 

"We believe this effort will pave the way for further expanding the availability of tests authorized for screening asymptomatic individuals, help bolster existing and new testing programs and increase consumer access to testing," Jeff Shuren, MD, director of the FDA’s Center for Devices and Radiological Health, and Tim Stenzel, MD, PhD, director of the Office of In Vitro Diagnostics, said in a news release. 

Some rapid tests are less accurate in asymptomatic people, Politico reported. But the FDA's updated policy takes into account that repeated testing for screening purposes can improve the overall accuracy of test results. 

The FDA said it will allow companies to apply to market over-the-counter tests for at-home or point-of-care use if they can provide evidence the test performs well in people with symptoms of COVID-19 and that repeated testing can help mitigate false results. 

Read the FDA's full news release here. 

https://www.beckershospitalreview.com/supply-chain/fda-to-allow-sale-of-covid-19-tests-without-studying-their-efficacy-in-asymptomatic-people.html

Majority of transplant recipients didn't develop antibody response after 1st COVID shot: study

 Of 436 solid organ recipients who received their first dose of the COVID-19 vaccine, antibodies were detected in 76 participants, according to a research letter published March 15 in JAMA.

Because immunocompromised people were not included in messenger RNA vaccine trials, researchers set out to capture vaccine response among organ transplant recipients. 

They recruited 436 participants across the U.S. who received their first COVID-19 shot between Dec. 16, 2020, and Feb. 5, 2021. None of the participants had a previous confirmed COVID-19 infection. 

A median of 20 days after receiving the vaccine, 17 percent of participants developed a positive antibody response, according to the study. Researchers noted that participants receiving anti-metabolite maintenance immunosuppression therapy were less likely to develop an antibody response than those who were not on such therapy. Older transplant recipients were also less likely to have a detectable immune response. 

"These findings of poor antispike antibody responses in organ transplant recipients after the first dose of mRNA vaccines suggest that such patients may remain at higher early risk for COVID-19 despite vaccination," the report said. "Deeper immunophenotyping of transplant recipients after vaccination, including characterization of memory B-cell and T-cell responses, will be important in determining vaccination strategies as well as immunologic responses after the second dose." 

To view the full report, click here.

https://www.beckershospitalreview.com/public-health/majority-of-transplant-recipients-didn-t-develop-antibody-response-after-1st-covid-19-shot-study-shows.html

Screening for 'Biotech Stocks That Could Double In 12 Months'

 Biotech stocks are risky investment bets that can swing an investor's fortunes in a big way. An investment decision backed by careful scrutiny and analysis — of a company's pipeline, collaborations, fundamentals, key make-or-break events and cash runway — can fetch disproportionate returns.

Here are three biopharma stocks that have the potential to more than double from current levels:

• Immatics IMTX 25.97%
• FibroGen, Inc. FGEN 0.21%
• Replimune Group, Inc. REPL 0.64%
• Immatics: Immatics is a clinical-stage biopharma engaged in the discovery and development of T cell directing cancer immunotherapies.

The shares of the German biotech were listed on the Nasdaq in July 2020 following its business combination with Arya Sciences Acquisition Corp, a SPAC sponsored by Perceptive Advisors.

The Pipeline: The company's T cell receptor (TCR)-based immunotherapies offer a targeted therapy to patients with high medical need. It has two lead product classes, namely engineered Adoptive Cell Therapies, or ACTengine, and antibody-like TCR Bispecifics, or TCER.

ACTengine is based on genetically engineering patients own T cells — a type of blood cells that are key to the immune system — with a TCR to recognize the cancer target. This would program the T cells to attack the tumor. These engineered T cells are then multiplied in labs and reinfused into the patients to treat the tumor.

The product candidates belonging to the class ACT are IMA201, IMA 202 and IMA203, which are in Phase 1 trials, as well as IMA204, which is in preclinical development. IMA301 is preclinical stage ACT allo product candidate.

IMA401 and IMA402 are two preclinical TCR bispecifics candidates.

The company has a string of partnerships with large biopharma companies such as Amgen Inc. AMGN 1.89%, Bristol-Myers Squibb Company BMY 0.64% and GlaxoSmithKline plc GSK 0.08%.

"Overall, we view TCR approaches as potentially transformational for the solid tumor therapeutic space, with the ability to target a wide range of antigens not accessible by CAR-T or classical antibody approaches," SVB Leerink analyst Jonathan Chang said in a note.

Although competition is steadily increasing, Immatics' comprehensive TCR-based immunotherapy approach will expand the potential utilization of TCRs across a broad range of tumor types and stages, the analyst said. 

Cash and cash equivalents as well as other financial assets stood at $303.6 million as of Sept, 30, 2020, providing cash runway into 2023.

Upcoming Catalysts: Combined initial data readout from its ACTengine product candidates, IMA201 and IMA 202, in solid tumors and IMA203 in hematologic malignancies and solid cancers in the first quarter.

Investigational new drug application filing for IMA204 in solid cancers in 2021.

IND filing for IMA301 in hematological and solid cancers in 2022.

IND filing for IMA-401 in solid cancers by year end 2022.

FibroGen: FibroGen focuses on advancing treatment options for anemia, fibrotic disease and cancer, leveraging its expertise in fibrosis and hypoxia-inducible factor biology.

HIF is a protein complex that plays a key role in the body's response to low oxygen concentrations and inflammation.

The Pipeline: FibroGen's anemia drug roxadustat is being developed along with AstraZeneca PLC AZN 0.16%. It is approved in China and Japan for chronic kidney disease-induced anemia, and awaits clearance in the U.S. and Europe for the same indication.

It is also being evaluated for anemia in myelodysplastic syndrome patients and chemotherapy-induced anemia.

FibroGen's fibrotic portfolio consists of pamrevlumab, which is being evaluated for multiple indications such as pancreatic cancer, Duchenne muscular atrophy, idiopathic pulmonary fibrosis and COVID-19.

The company's announcement March 1 regarding the FDA's decision to hold an Adcom meeting ahead of the roxadustat PDUFA date of March 20 led to a sell-off in shares. The stock has pulled back over 30% since the start of March.

"At this reduced share price we believe that the market is still undervaluing FibroGen's anti-CTGF antibody pamrevlumab, which is in phase 3 studies for three large indications, as well as roxadustat in China and Japan," SVB Leerink analyst Geoffrey Porges said in a note.

Even in the bear-case scenario of no approval for roxadustat in the U.S. and EU, FibroGen shares are worth $52/share, according to the analyst.

This, the analyst said, is an unlikely scenario. Approval for the drug in both dialysis-dependent and non-dialysis-dependent patients could push the stock value up to $85, he said.

The company recently initiated a Phase 3 study of pamrevlumab in combination with systemic corticosteroids in patients with ambulatory Duchenne muscular dystrophy.

FibroGen expects to end 2021 with cash in the range of $660 to $670 million.

Upcoming Catalysts: Phase 2 data for roxadustat in chemotherapy-induced anemia in the second-half of 2021.

Data from the Phase 3 study of roxadustat in anemia of myelodysplastic syndromes in the first half of 2022.

Resection data from the Phase 3 study of pamrevlumab in locally advanced pancreatic cancer in the second half of 2022.

Data from the Phase 3 study of pamrevlumab in DMD in the second half of 2022.

Replimune: Replimune is a pursuing a novel approach in taking on cancer with its oncolytic immunotherapy. It uses viruses that have been modified to selectively replicate in tumor cells and kill them. In a two-pronged strategy, oncolytic viruses kill tumors at the site of injection and also activate immune system to kill cancer cells anywhere in the body.

The company's lead candidate RP1 is being evaluated as a monotherapy as well as in combination with anti-PD1 antibodies such as Bristol-Myers Squibb's Opdivo and the Sanofi SNY 0.77%-Regeneron Pharmaceuticals, Inc. REGN 2.96% combo's Libtayo for multiple cancer types such as melanoma, non-melanoma skin cancer, micro instability-high cancers, non-small cell lung cancer, or NSCLC, and cutaneous squamous cell carcinoma, or CSCC.

RP2 and RP2 are being studied as monotherapy option and in combination with anti-PD1 antibodies against solid tumors.

"While the oncolytic virus landscape is competitive, we believe REPL has a lower risk profile given similarities between REPL's approach and the clinically validated T-Vec approach and the fact that REPL is being led by the same team that developed T-Vec," SVB Leerink analyst Chang said.

The cash balance of $493.3 million as of Dec. 31, the company said, will fund its operating expenses and capital expenditure requirements into the second half of 2024.

Upcoming Catalysts: Initial data for RP1 in new indications such as anti-PD1 failed NSCLC, anti-PD1 failed CSCC and CSCC solid organ transplant recipient patients due in 2021.

Updates across all RP1 programs anticipated in 2021.

Initial Phase 1 data for RP2 in combination with Opdivo due in 2021.

Initial single-agent data for RP3 in 2021.

Screening Criteria Used: Market cap of over $300 million.

Average trading volume of over 100,000.

Cash runway of two-plus years.

Sell-side rating of Buy or above.

Key upcoming catalysts.

https://www.benzinga.com/general/biotech/21/03/20197510/3-biotech-stocks-that-could-double-in-12-months

Vitamin D for All Over 50s to Prevent Cancer Deaths?

 Vitamin D supplementation for older healthy adults has been much debated. Recent attention has been focused on its potential for reducing the risk for and severity of COVID-19, but there is an older argument, boosted by recent evidence, for taking vitamin D to reduce deaths from cancer.

The recent data come from three meta-analyses published in 2019 that show a consistent and significant 13% reduction in cancer mortality with vitamin D.

Impressed with these data, a group of German researchers has proposed that all patients older than 50 years receive vitamin D supplements.

If all persons older than 50 in Germany were given a daily dose of 1000 IU of vitamin D, almost 30,000 cancer deaths a year could be prevented, and Germany's annual costs for cancer care would be slashed by more than €250 ($300) million, says the team.

Their article was published in Molecular Oncology on February 4.

"I was surprised by the magnitude of the effect that could be achieved with something as cheap as vitamin D, which costs almost nothing," lead author Tobias Niedermaier, PhD, an epidemiologist at the University of Heidelberg, Heidelberg, Germany, told Medscape Medical News.

Most of the financial savings would come from a reduction in costs for end-of-life cancer care, he noted.

"From a cost perspective, it makes a big difference if people die from cancer or later from some other disease," explained Neidermaier. "End-of-life care for a cancer patient in [their] last month of life is about four times higher than the medical care costs for people who die from other diseases like heart attack [or] cardiovascular diseases."

This is also the case in the United States. As an example, in a recent analysis, end-of-life care for a patient younger than 65 with stage IV breast cancer was $6099 per month, compared to $2988 for a patient who died from a cause other than cancer.

Germany provides healthcare insurance for 100% of its citizens through a mix of public and private contributions. In their study, Niedermaier and colleagues calculated that distributing vitamin D 1000 IU/d to every person older than 50 in Germany would cost around €900 ($1072) million but would result in savings of €1.16 ($1.9) billion.

This represents a net saving of €254 ($302) million annually, or approximately 0.4% of Germany's total drug expenditure in 2018. Moreover, 321,671 years of life would be saved.

In the United States, distributing a 5-cent vitamin D tablet to persons older than 50 would cost about $2.2 billion per year but would prevent 78,000 cancer deaths, save $3.7 billion, and endow older Americans with an additional 870,000 years of life.

An American expert who led one of the meta-analyses that acted as a springboard for the Niedermaier study agrees that the evidence that vitamin D reduces cancer mortality is indeed impressive.

"All of the trials showed a signal for risk reduction quite similar in magnitude," commented JoAnn Manson, MD, chief of the Division of Preventive Medicine at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, Boston, Massachusetts. "There was a 13% reduction that was quite strongly significant for cancer deaths," she said.

Despite the impressive results regarding cancer mortality, vitamin D did not appear to have any effect on cancer incidence in any of the studies. Manson said this finding is important: "There was really no reduction in cancer incidence, suggesting that vitamin D supplementation may affect tumor biology, rather than the initiation of cancer," she said. "It may be affecting the invasiveness of the cancer, its aggressiveness, how likely it is to metastasize."

Manson supports supplementation with vitamin D at a dose of 1000 IU. "I think [for] anyone with any concern about the amount of vitamin D they're getting, it would be really reasonable for them to take at least 1000 IU a day, especially if they're over the age of 50," she said.

However, when it comes to population-based approaches, Manson prefers to focus on the food supply: "Food fortification is going to go a long way," she said. "Lots of countries don't have it. They should seriously consider policies of food fortification as the first line of defense." (In the United States, vitamin D fortification is mandatory only for infant formula.)

A drug-repurposing expert expressed a note of caution about the proposal. "There's evidence to suggest that increasing our intake of vitamin D would be a good thing to do," commented Pan Pantziarka, PhD, "but it's a very hard thing to prove a population-level [benefit]. The only way to do this is to look at prospective data in randomized control trial."

Pantziarka is head of the Repurposing Drugs in Oncology (ReDO) project, an international collaboration between US-based GlobalCures and Belgium's Anticancer Fund that seeks new indications for existing medications. ReDO provides grants for researching drugs that lack commercial backing. The organization has just signed up to support a randomized controlled trial called VidMe in Belgium and Hungary that is testing the use of vitamin D for patients with cutaneous malignant melanoma.

There have already been numerous studies of vitamin D and oncology outcomes, beginning with a trial led by veteran vitamin-D researcher Cedric Garland, MD, that appeared in The Lancet in 1985.

Pantziarka pointed out that there is "so much conflicting data.... When you look down into the detail, you find that even the recommended daily dose is subject to huge controversies, and the effects of vitamin D are modified quite strongly by things like body mass index [BMI]."

The relationship between body weight and benefit from vitamin D was highlighted in results of the VITAL trial, conducted in Brigham and Womens Hospital in Boston by Manson.

With 27,416 participants, this is the largest vitamin D study by far. It is comparing daily doses of 2000 IU of vitamin D (cholecalciferol) and 1 g of marine n-3 fatty acids, separately and in combination, against placebo. Women make up 50.6% of the participants, and 20.2% are Blacks.

Initial 5-year data from VITAL were published in the New England Journal of Medicine in 2019. The article, which detailed oncology outcomes, shows that deaths from cancer were 17% lower in the vitamin-D arm. A post hoc analysis in which the first 2 years of data were excluded to account for a latency period found that the effect was even greater (a 25% reduction).

Manson explained the reasoning behind this post hoc analysis: "You're not really expecting that in the first few days ― or even the first year ― of taking vitamin D supplements, that's going to lower your risk of dying from cancer; you suspect that there's a latency involved. In cancer, even cancer death, the tumor takes a while to cause mortality.

"The 25% risk reduction [in the post hoc analysis] was statistically significant, so the bottom line is, I do think there's biological plausibility here," Manson said.

VITAL will continue to accrue data for at least 2 years because there are still some unanswered questions, according to Manson.

Benefit Only in Normal Weight, Not in Obese?

One of the questions that need to be clarified regards the differential effect that vitamin D has with respect to BMI or body weight. When the VITAL data were reanalyzed for people with a normal BMI (<25), the cancer-mortality risk reduction was 40%, said Manson, but there was no benefit for individuals whose BMI was in the overweight or obese range.

Other studies confirm these findings. It's possible that vitamin D has greater bioactivity for people with healthy weight, said Manson.

A study by a Harvard team that included Manson and that was published last year found that obesity does indeed modify vitamin D efficacy. Healthy adults were treated for 3 months with either placebo or vitamin D₃ at doses of 1000, 2000, or 4000 IU/d. More than half the group (56%, n = 141) were obese, and all were Blacks.

The team used suppression of parathyroid hormone (PTH) as a surrogate for vitamin D activity, said lead author Edward Giovannucci, MD, ScD, professor of nutrition and epidemiology at the Harvard School of Public Health. In the persons of normal weight, there was a clear dose response between vitamin D and suppression of PTH. By contrast, in the individuals with obesity, 1000 IU of vitamin D dramatically reduced PTH, but there was no further reduction with the higher vitamin D doses.

"While it is not surprising that overweight people have higher PTH due to generally lower vitamin D, we cannot completely overcome the effect of higher body weight by giving more and more vitamin D," Giovannucci told Medscape Medical News,

Translating the Proposal to the United States

How might the estimates for Germany translate to the United States? A quick calculation suggests it could save $1.5 billion.

In the United States, there are approximately 118 million people older than 50, and around 610,000 persons older than 50 die of cancer each year.

Assuming that all the persons older than 50 are provided with the cheapest brand of vitamin D 1000 IU, at 5 cents per tablet, a strategy similar to that advocated by Niedermaier and colleagues would cost $18.25 per year per person, or $2.2 billion per year across the United States.

On the basis of US costs for end-of-life cancer care provided in the German article, this would result in savings of $3.7 billion for families, government, and insurers in the United States and a net benefit (after paying for the vitamin D) of $1.5 billion.

Americans would gain an additional 870,000 years of life per year. In a very conservative scenario in which end-of-life costs are disregarded, the cost-effectiveness ratio is $2529 per life-year saved.

Niedermaier and colleagues found that vitamin D 400 IU/d and 1000 IU/d were "cost saving," that is, there was no extra cost per life-year saved because of the healthcare savings. The highest dose ― 2000 IU/d ― cost €692 ($830) per extra life-year saved.

The researchers found that in a worst-case scenario, there was a 4% reduction in cancer mortality, rather than a 13% reduction. In this scenario, the cost per life-year saved for vitamin D 1000 IU/d was €5506 ($6600).

By contrast, the authors indicate that letrozole costs $71,084 per life-year saved, and atezolimumab costs $94,965 for each extra year of life. In Germany, FOLFIRI plus cetuximab for RAS wild-type metastatic colon cancer confers an extra year of life at a cost of €36,360 ($44,000).

The authors conclude, "Our results suggest that daily vitamin D supplementation in the German population aged 50 years and older for reducing cancer mortality would be overall cost saving, or at least highly cost-effective."

The study was funded by the German Cancer Aid. Neidermaier, Manson, Pantziarka, and Giovannucci have disclosed no relevant financial relationships.

Mole Oncol. Published online February 4, 2021. Full text

https://www.medscape.com/viewarticle/947603

Moderna has begun testing its COVID-19 vaccine on young children

 Moderna has begun testing its COVID-19 vaccine on young children, the company announced Tuesday. The study, called KidCOVE, is testing Moderna's vaccine candidate in children ages 6 months to less than 12 years old.

"It is humbling to know that 53 million doses have been administered to people in the U.S.," Stéphane Bancel, chief executive officer of Moderna, said in a statement. "We are encouraged by the primary analysis of the Phase 3 COVE study of mRNA-1273 in adults ages 18 and above and this pediatric study will help us assess the potential safety and immunogenicity of our COVID-19 vaccine candidate in this important younger age population."

Moderna plans to enroll approximately 6,750 pediatric participants in the U.S. and Canada in the two-part study. In part 1, each participant ages 2 years to less than 12 years may receive one of two dose levels, while each participant ages six months to less than 2 years may receive one of three dose levels. 

Following analysis, researchers will determine which dose will be used in part 2 of the study, which involves a placebo for comparison. 

Children participating in the study will be followed for 12 months after receiving the second vaccination. The vaccine's effectiveness, as well as its safety and reactogenicity (potential side effects like injection-site pain, headache and fever) will be studied. 

The National Institute of Allergy and Infectious Diseases (NIAID) and the Biomedical Advanced Research and Development Authority (BARDA), part of the Office of the Assistant Secretary for Preparedness and Response at the U.S. Department of Health and Human Services, are helping conduct the study.

Moderna announced in December that it had launched a similar trial involving 3,000 adolescents ages 12 to less than 18.

On CBS News' "Face the Nation" earlier this month, moderator Margaret Brennan asked Dr. Anthony Fauci about vaccinations for high school students. 

"We project that high school students will very likely be able to be vaccinated by the fall term, maybe not the very first day, but certainly in the early part of the fall for that fall educational term," Fauci said. "Elementary school kids, we're doing this what's called age de-escalation studies to make sure it's safe and immunogenic in them. They likely will be able to get vaccinated by the very first quarter of 2022."

CBS News' David Begnaud recently met two sisters, Dylan and Blair Davis, who are participants in Moderna's adolescent vaccine trials in Houston, Texas. Their mother, Dr. Mendy Jeter, said she wanted to get her daughters protected.

"It would protect us. It would protect their grandparents and anyone else," she said. 

That's why the girls' parents, who are both doctors, applied to at least three vaccine trials. "I wanted them to be an example, to set an example, to say, 'Hey, this vaccine is safe.'... We actually, as doctors, trust our children getting this shot," Jeter said.

"If our kids can help get this trial approved for other teenagers, I think it'll make everyone feel better and be in a safer place," she added.

Vaccines by Johnson & Johnson, Pfizer-BioNTech and Moderna are currently being used in the U.S. The Moderna shots were first shipped out in December, after the Food and Drug Administration authorized their emergency use for people ages 18 or older. Johnson & Johnson's vaccine is also currently authorized only for ages 18 and up, while Pfizer's can be used for ages 16 and up.

The Moderna and Pfizer vaccines had similar, very high rates of effectiveness in adult studies. Both vaccines require two doses, while Johnson & Johnson's is only a single shot.

The U.S. has now administered over 100 million doses of COVID-19 vaccine, according to figures posted Friday by the Centers for Disease Control and Prevention. President Biden set a goal of 100 million vaccinations in his first 100 days in office, which the country is on track to reach well ahead of schedule. He also said he would direct all states to make all American adults eligible for the COVID vaccine by May 1.

https://www.cbsnews.com/news/covid-19-vaccine-children-moderna/

Trump urges all Americans to get COVID vaccine

 Former President Trump urged all Americans to get the coronavirus vaccine in a Fox News exclusive interview on Tuesday, touting its efficacy as both "a safe vaccine" and "something that works."

Trump was asked by "Fox News Primetime" host Maria Bartiromo whether he would advise viewers to get the COVID-19 vaccine developed under his administration's Operation Warp Speed.

Unlike President Joe Biden, Trump did not publically receive the vaccine, but Fox News confirmed earlier this month that both he and former first lady Melania Trump received their vaccines privately in January at the White House.

"I would recommend it and I would recommend it to a lot of people that don't want to get it and a lot of those people voted for me, frankly," Trump told Bartiromo. 

"It is a great vaccine. It is a safe vaccine and it is something that works," he said.

Trump took the opportunity to criticize what he sees as Biden’s attempt to take credit for his vaccine accomplishments, telling Bartiromo that without his administration's efforts to obtain FDA emergency approval, Americans wouldn't receive a vaccine for years.

"We have been working around the clock and what I got the FDA to do, this would have happened... in many, many years from now if I didn't get involved," he said.

Trump lauded his administration for taking a "big bet" to manufacture "the vaccine before we really knew what works."

"We saved many months and millions of lives by doing that," he said.

"It works incredibly well. 95%, maybe even more than that...and it is really saving our country and it is saving frankly the world."

https://www.foxnews.com/media/trump-urges-all-americans-to-get-covid-vaccine-its-a-safe-vaccine

GE Healthcare debuts pocket-sized, wireless ultrasound

 GE Healthcare launched a new handheld, wireless ultrasound device, capable of scanning anywhere within the body and small enough to be carried around in a clinician’s pocket.

The Vscan Air is an addition to the company’s family of portable ultrasound systems which first launched in 2010. The device connects with the user’s own smartphone, and includes a two-sided design—when flipped over, it can be used for both shallow and deep tissue without switching probes during exams.

“Now more than ever, clinicians need smaller and smarter tools that increase access and efficiency both in and outside of the four walls of the hospital,” with ultrasound becoming an essential point-of-care tool, said Anders Wold, president and CEO of GE Healthcare’s global ultrasound division. 

According to the company, heart and lung ultrasounds have been shown to be as helpful as X-ray and CT scans when treating patients with COVID-19, while being faster and more efficient, especially when it comes to disinfecting equipment.

The Vscan Air system is built to withstand cleaning procedures, as well as water exposure, drops and extreme temperatures, the company said. In addition, patient data and images are transmitted within the provider’s network, and anonymized images can be shared with patients directly after a scan.

Late last year, GE Healthcare secured an FDA clearance for its artificial intelligence-powered ultrasound system for echocardiograms. The software automatically detects points in a 2D image used to measure the size of the heart’s left ventricle, to help diagnose heart failure and cardiovascular disease. The system also semi-automatically measures blood flow and velocity within the body.

https://www.fiercebiotech.com/medtech/ge-healthcare-debuts-pocket-sized-wireless-ultrasound