Noninvasive imaging strategy detects dangerous blood clots in the body

 Atrial fibrillation -- an irregular and often rapid heart rate -- is a common condition that can cause clots to form in the heart that may then dislodge and flow to the brain, potentially leading to a stroke. The standard way to detect these clots requires patients to be sedated and to have a fairly large tube inserted down the throat and esophagus for a transesophageal ultrasound. Investigators at Massachusetts General Hospital (MGH) have now developed and tested a targeted contrast agent to detect and image these clots noninvasively. They verified the potential of this strategy in a study published in JACC: Cardiovascular Imaging.

The agent has a strong affinity for fibrin, a component of blood clots, and is detected with a radioactive copper tag. "The idea behind the technology is that the agent will find and bind to blood clots anywhere in the body -- not just in the heart -- and make the clots detectable like a bright star in the night sky," says senior author David Sosnovik, MD, FACC, director of the Program in Cardiovascular Imaging within MGH's Martinos Center for Biomedical Imaging and an associate professor of Medicine at Harvard Medical School. "In some ways this is analogous to doing a smart search with a search engine such as Google, where the search terms one uses guide the search. We inject the agent into a small peripheral vein and it circulates throughout the human body on its search for clots." If it doesn't find any clots, then it's rapidly excreted from the body; however, if it finds a clot and binds to it, clinicians can detect it with an imaging technique known as positron emission tomography.

Sosnovik and his colleagues first examined how the agent reacts (specifically, its metabolism and pharmacokinetics) in eight healthy volunteers. After injection, the agent was initially stable within the body and then was cleared from tissues within several hours, suggesting that it was safe. Next, the team administered the agent to patients with atrial fibrillation, some with clots in the heart and some without. Imaging tests of the heart revealed bright signals within the clots that were not seen in patients without clots.

"Obviously much more work and many more studies will need to be done before this changes routine clinical practice, but this first-in-human study is an important step," says Sosnovik. "Importantly, this smart or molecularly targeted agent can be used to detect clots anywhere in the body."

Sosnovik stressed that the multidisciplinary nature of this project was critical to its success, with vital roles played by diverse scientists, including Peter Caravan, PhD, who invented and developed the study's agent and is the co-director of MGH's Institute for Innovation in Imaging. "This probe was invented and optimized in my laboratory by a dedicated team of chemists and biologists through the support of the National Heart Lung and Blood Institute of the National Institutes of Health," says Caravan. "It is extremely gratifying to see these years of effort come to fruition with a fibrin-specific PET probe with the potential to make a real impact on human health."

Others playing a major role in the study included David Izquierdo-Garcia, PhD, an assistant in Biomedical Engineering at MGH, and Ciprian Catana, MD, PhD, director of Integrated MR-PET Imaging at MGH's Martinos Center for Biomedical Imaging. Izquierdo-Garcia, the lead author on the paper, and Catana both stressed the innovative nature of the imaging platform used in the study. "Not only did we use a novel molecular imaging probe in humans for the first time, but also, this is one of the first studies to fully explore the synergies and advantages of integrated PET-MRI scanners," says Izquierdo-Garcia.

"It is a privilege to work at the Martinos Center for Biomedical Imaging and be part of multidisciplinary teams that collaborate to develop and apply cutting-edge imaging technologies," adds Catana. "We were the first site in the U.S. to install a fully integrated PET-MRI scanner and have played a major role in the advancement and clinical translation of this technology."

Additional co-authors include Pauline Désogère, PhD, Anne L. Philip, MPH, Choukri Mekkaoui, PhD, Rory B. Weiner, MD, Onofrio A. Catalano, MD, Yin-Ching Iris Chen, PhD, Doreen DeFaria Yeh, MD, and Moussa Mansour, MD.

Funding for the study was provided by the National Institutes of Health.

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Story Source:

Materials provided by Massachusetts General Hospital. Note: Content may be edited for style and length.

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Journal Reference:

1. David Izquierdo-Garcia, Pauline Désogère, Anne L. Philip, Choukri Mekkaoui, Rory B. Weiner, Onofrio A. Catalano, Yin-Ching Iris Chen, Doreen DeFaria Yeh, Moussa Mansour, Ciprian Catana, Peter Caravan, David E. Sosnovik. Detection and Characterization of Thrombosis in Humans Using Fibrin-Targeted Positron Emission Tomography and Magnetic Resonance. JACC: Cardiovascular Imaging, 2021; DOI: 10.1016/j.jcmg.2021.08.009

https://www.sciencedaily.com/releases/2021/11/211101105402.htm

Children, adults equally vulnerable to co infection, but children less likely to become sick

 New research addresses the misconception that children are less susceptible to infection with the new coronavirus. According to a recent report in JAMA Pediatrics, children and adults have similar risks of becoming infected with SARS-CoV-2, but a much larger proportion of infected children do not show symptoms of COVID-19. When one household member is infected, there is a 52% chance they will transmit it to at least one other person with whom they live.

The findings are based on the Coronavirus Household Evaluation and Respiratory Testing (C-HEaRT) study led by the Centers for Disease Control and Prevention (CDC) in collaboration with investigators at University of Utah Health, Columbia University, Marshfield Virology Laboratory, and Abt Associates.

"Often, it seemed like children weren't sick because they didn't have any symptoms," says Christina Porucznik, Ph.D., professor of public health at U of U Health, who led investigation of 189 families in Utah. "But some were actually infected, and they could still spread COVID-19."

Early in the pandemic, reports indicated that children accounted for the minority of COVID-19 cases. However, the observation was not able to distinguish between two scenarios. One was that children were less susceptible to infection. Another was that reported case rates in children were artificially low because they did not show symptoms, and therefore were not tested.

To better understand infection dynamics, the C-HEaRT study followed 310 households with one or more children aged 0 to 17 years in Utah and New York City. More than 1,236 study participants submitted samples for weekly molecular testing (PCR) for SARS-CoV-2 infections and completed weekly questionnaires about symptoms. On average, each person was observed for 17 weeks, and the report included a total of 21,465 person-weeks of surveillance time. The results were from September 2020 through April 2021, before the Delta variant emerged in the U.S.

The study showed that:

• Children and adults 18 years and older had similar rates of infection.
• Children in different age groups (birth to 4 years; 5 to 11 years; 12 to 17 years) also had similar rates of infection. Infection rates in each group were between 4.4 to 6.3/1,000 person-weeks.
• About half of the cases in children were symptomatic, compared with 88% of adult cases.
• In households with one or more infected individuals, the overall average household infection risk was 52%.
• The mean household infection risk was 40% in Utah and 80% in New York City.

More research will need to be done to investigate whether differences in housing density, the timing of emergence of the Delta variant, or other factors contributed to differences in household transmission rates in Utah and New York. Additionally, infection rates and household infection risk may be higher in the general population since study participants could be more likely to carry out COVID-19 prevention behaviors.

This study's results highlight that many infections in children go undetected, underscoring the need for surveillance testing and for children to continue public health safety measures to protect the people around them, Porucznik says. "We know that until kids can be vaccinated, it's still important for them to wear masks when they're in groups and to keep them apart," she says. "And most of all, when they are sick, keep them home."

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Incidence rates of SARS-CoV-2 similar for children, adults

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More information: Fatimah S. Dawood et al, Incidence Rates, Household Infection Risk, and Clinical Characteristics of SARS-CoV-2 Infection Among Children and Adults in Utah and New York City, New York, JAMA Pediatrics (2021). DOI: 10.1001/jamapediatrics.2021.4217

https://medicalxpress.com/news/2021-11-children-adults-equally-vulnerable-coronavirus.html

Treatments for Alzheimer's sitting on pharmacy shelves for decades?

 Two drugs approved decades ago not only counteract brain damage caused by Alzheimer's disease in animal models, the same therapeutic combination may also improve cognition.

Sounds like a slam dunk in terms of a cure—but not yet. Researchers currently are concentrating on animal studies amid implications that remain explosive: If a surprising drug combination continues to destroy a key feature of the disease, then an effective treatment for Alzheimer's may have been hiding for decades in plain sight.

A promising series of early studies is highlighting two well known medicine cabinet standbys—gemfibrosil, an old-school cholesterol-lowering drug, and retinoic acid, a vitamin A derivative. Gemfibrosil, is sold as Lopid and while it's still used, it is not widely prescribed. Doctors now prefer to prescribe statins to lower cholesterol. Retinoic acid has been used in various formulations to treat everything from acne to psoriasis to cancer.

The two drugs are being studied for their robust impact on the brain and a potential new role that could one day thrust them into fighting what is now an incurable brain disease. Both medications have an uncanny capability to zero in on the brain's astrocytes, cells that originally got their name because they look like stars. But astrocytes are intimately involved in a key process that progressively—and insidiously—destroys the brain.

Researchers at Rush University Medical Center in Chicago have found that astrocytes may be responsible for the accumulation of amyloid beta (Aβ), the gooey plaque that damages neurons. As a result, these star-like cells aid in the cascade of deleterious events that rob people of their sense of self, their memories, and ultimately steals their lives.

The team of medical investigators also has discovered that gemfibrozil and retinoic acid, when used in combination, force astrocytes to reverse their destructiveness, and instead reduce amyloid beta in the brain—improving cognitive function. The findings suggest that, perhaps in the not-too-distant future, these drugs can be repurposed to coax astrocytes into a beneficial role, serving as Aβ "clearing machines," eliminating the accumulation of plaques and preventing Alzheimer's from unraveling the brain.

"From a therapeutic angle, these results suggest that low-dose [gemfibrozil and retinoic acid] might be repurposed as a treatment for reducing the plaque burden and improving cognition," wrote Dr. Sumita Raha, first author of a paper published in Science Translational Medicine.

"Astrocytes are a type of glial cell that are implicated in the buildup of amyloid beta in Alzheimer's disease," Raha added about the drug duo. Along with her Rush Medical Center colleagues, the team is proposing that rather than being intricately involved in the promotion of Aβ accumulation "astrocytes could be induced to take up and destroy Aβ fibrils with an orally ingested combination of drugs that are approved for other indications."

Astrocytes studied in cell cultures and in Alzheimer's mouse models were stimulated by retinoic acid to phagocytose—destroy Aβ—through the activation of the low-density lipoprotein cholesterol receptor and triggered to subsequently degrade Aβ in lysosomes by the cholesterol-lowering drug gemfibrozil.

Earlier research led by Raha's colleague, Dr. Kalipada Pahan, also of Rush, and an author of the current study, found that a combination of gemfibrozil and retinoic acid accelerated the formation of lysosomes in mouse brain cells. Lysosomes are the organelles that contain digestive enzymes and are involved in the breakdown of excess or worn-out cell parts. The word organelle means "little organ," a term for the components in cells with specialized functions, such as the Golgi apparatus or mitochondria.

Raha, Pahan, and colleagues discovered that gemfibrosil and retinoic acid also caused mouse astrocytes to take in more amyloid beta from outside of the cell. Their experiments revealed that the drug combination activated a receptor called PPARα, which encouraged astrocytes to destroy the mind-damaging amyloid, the cause of plaques. PPARα stands for peroxisome proliferator-activated receptor-alpha. PPARα is a transcriptional factor that regulates the expression of genes involved in fatty acid oxidation and is also a major regulator of energy homeostasis. PPARα is critical in the elimination of amyloid beta, Aβ.

Gemfibrosil is an old drug, first patented in the 1968 as a cholesterol reducer. Retinoic-acid-based drugs are even older. For example, Tretinoin, a retinoic acid medication, was patented in 1957. If the gemfibrosil/retinoic acid drug combination ultimately works in humans, then the Chicago-based team will have ushered into use a new treatment made up of two very old medications.

Although the team at Rush University Medical Center is well into its pursuit of the two-drug combination, it's not yet known when the experiments might advance to a full-blown human clinical trial. Yet, along with identifying a potential two-drug approach to Alzheimer's disease, the Chicago experiments also have added to the scholarship about the biology of astrocytes in the brain.

Astrocytes, or astroglia, as they are also known, are a type of glial cell, and they dramatically outnumber neurons. Some estimates suggest there is a fivefold difference between the two types of brain cells favoring astrocytes. While neurons are the cells of all higher functions, such as learning and memory, astrocytes play a major role regulating increases in intracellular calcium. Upping intracellular calcium is required to maintain astrocyte-to-astrocyte and astrocyte-to-neuron communication, studies have shown.

Yet as the gemfibrosil/retinoic acid combination evolves as a potential Alzheimer's therapy, the larger story about drugs to treat Alzheimer's has been a tale marred by setbacks and disappointments for decades. The most recent involves questions that arose following the approval in June of Biogen's Aduhelm, a medication that carries a breathtakingly high price tag—$56,000 a year in the United States.

Medical experts voiced concern about studies leading to the drug's approval. Taken as a whole, the research demonstrated mixed results. But the drug, which is administered as an infusion, was fast-tracked through the U.S. Food and Drug Administration's authorization process.

Worse, Aduhelm is one of slightly more than a half dozen drugs approved in a quarter century to treat Alzheimer's, a disease that is rapidly becoming one of the largest health crises on the planet, according to the World Health Organization.

Currently, an estimated 55 million people globally have Alzheimer's disease, and that number could explode to more than 152 million worldwide by 2050 unless a cure is found.

In Chicago, meanwhile, the team at Rush University Medical Center has found a novel way to control Alzheimer's progression in mouse models using drugs off the shelf. "We found that the same combination of gemfibrosil and retinoic acid enhanced the uptake of Aβ from the extracellular space and its subsequent degradation in astrocytes through a PPARα-dependent pathway," Raha asserted. "These findings uncover a new function of PPARα in stimulating astroglial uptake and degradation of Aβ and suggest possible repurposing of gemfibrosil-retinoic acid combination therapy for Alzheimer's disease."

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Cholesterol drives Alzheimer's plaque formation, study finds

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More information: Sumita Raha et al, Activation of PPARα enhances astroglial uptake and degradation of β-amyloid, Science Translational Medicine (2021). DOI: 10.1126/scisignal.abg4747

https://medicalxpress.com/news/2021-11-treatment-alzheimer-pharmacy-shelves-decades.html

Despite strong quarter, some wonder how long Gilead can rely on coronavirus drug

 Veklury, the antiviral drug for COVID-19, blew past Wall Street expectations in the third quarter, lifting what would have otherwise been a weak earnings season for its developer, Gilead.

During the three-month period, 2 million people received Veklury or a licensed generic version of it, according to Gilead. That use translated to almost $2 billion in sales, nearly triple what analysts had forecasted.

Yet some wonder how long Veklury can make up for the rest of Gilead’s business, which fell 3% over the same timeframe. More people worldwide are getting vaccinated, while coronavirus cases are on the decline following a major surge due to the delta variant.

Competition is also nearing, as Merck & Co. and others advance oral antiviral drugs that are generally considered more convenient than Veklury, which is used in hospitalized patients and given via an intravenous infusion.

Veklury is "not likely to be a sustainable franchise in our view given our expectations for COVID waning and small molecule antiviral availability," wrote Brian Abrahams, an analyst at RBC Capital Markets, in a note to clients.

Still, Abrahams and his team believe Veklury’s strong sales provide Gilead with "a highly effective hedge against pandemic headwinds to their other franchises." The company recorded $7.4 billion total product sales in the quarter, up 13% from the same period a year prior.

As one of the earliest approved treatments for COVID-19, Veklury has been a valuable asset to both doctors and Gilead. Over 60% of patients hospitalized with the disease in the U.S. receive Veklury, according to the company. On a Thursday call with investors, executives amended their full-year revenue outlook for the drug, increasing it from the old range of $2.7 billion to $3.1 billion to a new one of $4.5 billion to $4.8 billion.

Despite that change, leadership noted how Veklury’s performance is tied to patient hospitalizations. So if case numbers go down, sales are likely to follow.

"After the wave of infections and hospitalizations in recent months, we believe we have moved past the peak of the pandemic for the year," said Andrew Dickinson, the company’s chief financial officer.

"We continue to expect that Veklury will play an important role in the treatment of patients with COVID -19 globally," he added. "However, assuming we do not experience another surge, we expect Veklury revenue to step down significantly in the fourth quarter."

Veklury may run into additional obstacles from Merck, which announced this month that an antiviral pill it’s been developing with partner Ridgeback Biotherapeutics dramatically reduced the number of hospitalizations from COVID-19, compared to a placebo, in a clinical trial.

More specifically, the pill lowered the risk of hospitalization or death by about 50% in patients with mild or moderate disease. Merck is now trying to secure an emergency authorization in the U.S. "as soon as possible," and, on the company’s own earnings call Thursday, executives forecasted between $5 billion and $7 billion in sales of the drug through the end of 2022.

Gilead has been working on oral antivirals too, though they aren’t as far along as Merck’s or other experimental treatments from Pfizer and Atea Pharmaceuticals. The company’s chief medical officer, Merdad Parsay, said data updates will be provided "as those molecules begin to mature," adding that one of the main aims is to provide alternative treatment options, especially in the outpatient setting.

Outside of COVID-19, Gilead is hoping to move the needle in cancer treatment after spending $27 billion last year on deals meant to establish it as a leader there. Among the assets it acquired are magrolimab, an experimental drug for blood cancers, and Trodelvy, an approved therapy for breast cancer.

Investors are now looking forward to data from key clinical trials testing those drugs, though they’ll have to wait a bit longer than expected. Gilead said Thursday that readouts from both trials have been pushed back to the first quarter of 2022.

The company’s cancer work has become a focal point — not only because of how much money it’s wagered, but also because of challenges to its core business of antiviral drugs. In HIV, for example, Gilead’s third quarter product sales were $4.2 billion, an 8% decline that reflected the loss of patent protection on the medicines Truvada and Atripla in the U.S.

"Success from any of the oncology programs or new indications could transform Gilead’s outlook by providing a real growth driver to their top line," wrote SVB Leerink analyst Geoffrey Porges in a note to clients.

https://www.biopharmadive.com/news/gilead-veklury-coronavirus-earnings-oncology-outlook/609160/

Idorsia sets itself up for failure

 Idorsia’s faith in cenerimod might be understandable in the context of lupus recently becoming an area for deal-making interest. But the group’s decision to press on into phase 3 trials after cenerimod today flopped in phase 2 seems reckless, and potentially sets the project up for an even bigger failure later on.

True, Idorsia has plenty of cash to burn – over CHF1bn ($1.1bn) of short-term liquidity at the end of September, to be precise – but its investors should today ask whether starting a large pivotal programme is wise. At best one cenerimod dose has shown hints of activity, but first running a confirmatory phase 2 trial to test this hypothesis prospectively would be more prudent.

The Care study toplined today tested four doses of cenerimod, an S1P receptor modulator. The highest, 4mg, showed a numerical improvement in the primary endpoint, mSLEDAI-2K score versus placebo at six months, Idorsia said today without giving any further efficacy details apart from revealing a nominal p value of 0.029 for the 4mg dose.

Non-significant

On the face of it this does seem promising, even ignoring the fact that, given the statistical penalty for analysing the four doses separately, the p value was highly non-significant.

But seasoned biotech investors will be aware that any benefit reported in a mid-stage trial would be expected to wane in the stricter setting of phase 3. We do not know the absolute benefit shown by cenerimod 4mg, but even a nominal p of 0.029 is hardly an overwhelming signal of efficacy, and such a borderline effect would be expected to be at an especially high risk of melting away in a pivotal trial.

Moreover, Idorsia appears to be hinting that there is a numerical dose-response effect in Care, but importantly it has not actually spelled this out. If the highest dose has done best this is clearly good, but Idorsia has revealed nothing about the numerical performance of any of the lowest three cenerimod doses.

Idorsia says 4mg was also associated with improvements in several patient subpopulations, especially those with severe disease, and on the SLE responder index, a four-point composite measure of activity in lupus. It did not say whether either would be incorporated into the phase 3 programme it now aims to discuss with regulators.

Finally, if 4mg is so good, with no toxicity penalty, why not test an even higher dose? The disappointment is the second to hit Idorsia in recent weeks; in mid-October its Fabry disease project lucerastat failed a pivotal study.

MS mechanism

S1P modulation is more commonly associated with drugs for multiple sclerosis, including Novartis’s Gilenya and Mayzent, and Idorsia/J&J’s recently approved Ponvory. Another positive for cenerimod, which Idorsia describes as highly selective with a bias for the S1P1 subtype, is that it had no impact on blood pressure or pulmonary function, which S1P1 receptor modulators are known to affect.

Still, this mechanism has hardly proved a resounding success in lupus. According to Evaluate Pharma two other projects, the S1P1/4/5 agonist prodrug KRP-203 and the S1P1 receptor antagonist amiselimod, were once studied in the disease, but they have seen no work since 2017.

Cenerimod carried modest sellside revenue forecasts, $108m in 2026, according to Evaluate Pharma, but these were likely predicated on Care serving as one registrational study, and a single phase 3 sufficing as the other. There will now be a lengthy delay while Idorsia undertakes two new phase 3 tests, whose likelihood of success must now be seen as remote.

Selected lupus projects acting on S1P (sphingosine-1-phosphate)
Project	Company	Mechanism	Lupus summary	Other indications
Cenerimod	Idorsia	S1P1 receptor modulator	Moving to ph3 after failing ph2	None
Mocravimod (KRP-203)	Kyorin/Novartis	S1P1/4/5 agonist prodrug	Abandoned after ph2	Ph2 in ulcerative colitis terminated
Amiselimod (MT-1303)	Biogen/Mitsubishi Chemical	S1P1 receptor inhibitor	Abandoned after ph1	Ph2 in ulcerative colitis enrolling; ph2 in relapsing/remitting MS completed
Source: Evaluate Pharma & clinicaltrials.gov. https://www.evaluate.com/vantage/articles/news/trial-results/idorsia-sets-itself-failure

US FDA approval tracker: October

 Delays and complete response letters dominated the FDA regulatory scene last month, including a knockback for the troubled pain project tanezumab. After 16 years, and 39 clinical trials, Pfizer and Lilly finally scrapped the whole development programme. Elsewhere, Oncopeptide’s Pepaxto was withdrawn from the US market after the confirmatory Ocean study showed overall survival concerns. The drug had gained accelerated approved for fifth-line multiple myeloma in February. In better news for biopharma, the green light for Roche’s Tecentriq as an adjuvant therapy in NSCLC came early. However, the label restricts Tecentriq’s use to PD-L1-expressing stage II-IIIA patients, and data from the competition looms. Merck & Co’s Keynote-091 trial, testing Keytruda in in stage IB-IIIA patients regardless of PD-L1 expression, is expected to yield data soon.

Notable first-time US approval decisions in October
Project	Company	Indication(s)	2026e sales by indication ($m)	Outcome
Cibinqo (abrocitinib)	Pfizer	Atopic dermatitis	1,035	No decision yet
Bimzelx (bimekizumab)	UCB	Plaque psoriasis	992	Delayed (inability to conduct facility inspections because of travel restrictions)
Vynpenta (avacopan)	Chemocentryx	ANCA-associated vasculitis	610	Approved
DaxibotulinumtoxinA	Revance	Glabellar lines	430	CRL (manufacturing deficiencies)
FT218	Avadel	Narcolepsy	332	Delayed (no new date disclosed)
Narsoplimab (OMS721)	Omeros	Haematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA)	298	CRL (additional data needed)
Scemblix (asciminib)	Novartis	3L chronic myeloid leukaemia	279	Accelerated approval (Philadelphia chromosome-positive CML in chronic phase) Full approval (with the T315I mutation)
Zimhi	Adamis	Opioid overdose	64	Approved (after two CRLs)
Mydcombi	Eyenovia	Pupil dilation agent	28	CRL (reclassified as a drug-device combination)
Raylumis (tanezumab)	Lilly/Pfizer	Osteoarthritis pain	24	CRL (negative adcom in March)
Rethymic (RVT-802)	Enzyvant, Sumitomo Dainippon Pharma	Paediatric patients with congenital athymia	16	Approved
Tyrvaya (OC-01)	Oyster Point	Dry eye disease	–	Approved
Xipere	Bausch Health/ Clearside	Macular oedema associated with uveitis	–	Approved
Kyzatrex	Marius	Primary and secondary male hypogonadism	–	No decision yet
Vuity (pilocarpine HCl ophthalmic solution 1.25%/ AGN-190584)	Abbvie	Presbyopia (age-related blurry near vision)	–	Approved
Source: Evaluate Pharma & company releases.

 

Advisory committee meetings in October
Project	Company	Indication	2026e sales by indication ($m)	Outcome
Comirnaty	Pfizer/Biontech	Covid vaccination in children aged 5-11	2,819	Recommended, given EUA on Oct 29
Spikevax	Moderna	Booster dose to individuals aged 65 and older, or at high risk owing to medical conditions or occupation	2,756	Recommended
Ad26.COV2-S	J&J	Booster dose to individuals aged 18 and older	767	Recommended
Pepaxto	Oncopeptides	In combination with dexamethasone for the treatment of adult patients with r/r multiple myeloma who have received at least four prior lines of therapy	552	Cancelled, Pepaxto withdrawn from US market (had accelerated approval)
Maribavir	Takeda	Adults with post transplant cytomegalovirus infection/disease	355	Recommended
Source: FDA ad com calendar & Evaluate Pharma.

 

Supplementary and other notable approval decisions in October
Product	Company	Indication (clinical trial)	Outcome
Tecartus	Gilead	Adult patients with r/r ALL (Zuma-3)	Approved
Dextenza	Ocular Therapeutix	Ocular itching associated with allergic conjunctivitis	Approved
Dupixent	Sanofi/ Regeneron	Asthma in ages 6-11 (Voyage)	Approved
Susvimo (Lucentis port delivery system)	Roche	Wet AMD (Archway)	Approved
Cortrophin Gel	ANI	Multiple sclerosis, rheumatoid arthritis, and nephrotic syndrome	Approved
Verzenio	Lilly	HR+ Her2- high risk early breast cancer (monarchE)	Approved
Keytruda	Merck & Co	1L cervical cancer plus chemo (whose tumours express PD-L1) also 2L as a single agent (Keynote-826)	Approved (2L converted to full approval from accelerated approval)
Tecentriq	Roche	Adjuvant treatment for adults with Stage II-IIIA NSCLC whose tumours express PD-L1≥1% (Impower-010)	Approved (~6 weeks early)
Biktarvy	Gilead	Low-dose tablet for HIV treatment in virologically suppressed children weighing at least 14 kg (Cohort 3)	Approved
Cyltezo (Humira biosimilar)	Boehringer Ingelheim	RA, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, plaque psoriasis, polyarticular juvenile idiopathic arthritis	Approved as interchangeable biosimilar
Tyvaso DPI	Mannkind/United Therapeutics	PAH and pulmonary hypertension associated with interstitial lung disease (Breeze)	CRL (deficiencies at contract manufacturer)
Myring	Mayne Pharma/ Mithra	Generic contraceptive ring	CRL (additional data)
Xeljanz	Pfizer	Ankylosing spondylitis (A3921120)	No decision yet
Olumiant	Lilly	Atopic dermatitis (Breeze-AD program)	No decision yet
Rinvoq	Abbvie	Atopic dermatitis, psoriatic arthritis and ankylosing spondylitis	No decision yet
Andexxa	Astrazeneca	Addition of edoxaban and enoxaparin (FXa inhibitors) to the label	No decision yet
Source: Evaluate Pharma & company releases. https://www.evaluate.com/vantage/articles/news/snippets/us-fda-approval-tracker-october-1

No Evidence Found Of In-Game COVID-19 Transmission For SEC 2020 Football Season

 As the COVID-19 pandemic continued during fall 2020, athletic conferences and leagues had to make critical decisions about how sporting competitions would be played. Like other organizations, the Southeast Conference (SEC) set protocols to monitor, manage and mitigate COVID-19 exposure during athletic events.

Researchers at Texas A&M University recently analyzed contact tracing data recorded during official conference games and SEC testing data for athletes in play. They found that competition during the fall 2020 football season was relatively safe.

Between Sept. 26 and Dec. 19, 2020, a total of 1,190 players had 109,762 opposing player interactions over the 64 SEC regular season games. Benika Dixon and several other researchers at the Texas A&M University School of Public Health analyzed the data from these interactions and found that most of the interactions were fleeting.

“Although there are a lot of these interactions that happen during a football game, they tend to be very brief, with the majority of them being less than 26 seconds,” Dixon said. “We also looked at recurring interactions between players and, very similarly, found that total contact was brief as well. Most contacts that were recurring with two players were still less than 97 seconds.”

Only 13 opponent pairs had in-game contact that exceeded the Centers for Disease Control and Prevention’s 15-minute threshold for close contacts. Of those 13 pairs, none tested positive for COVID-19 in the 14 days prior to or after the game.

“For this particular paper, we looked at the player interaction, but we did not look at interactions that occurred between players and referees or players and coaches,” Dixon said. “We also looked strictly at gametime contact, so we didn’t take into consideration any contacts that may have happened pre- or post-game. I think there’s definitely an opportunity to expand on this research and look at other types of interactions that occur.”

The findings indicate that through the use of innovative strategies, infectious diseases such as COVID-19 can be prevented and monitored during sporting competitions. Dixon said this proves the importance of prevention protocol: “Gameplay was relatively safe when implementing strategies such as contact tracing, and overall, it showed the importance of utilizing protection strategies during athletics.”

“This study shows the importance of public health prevention strategies to allow athletic activities during an infectious disease pandemic,” said School of Public Health Dean Shawn Gibbs, who serves on the SEC Medical Task Force.

https://today.tamu.edu/2021/10/29/researchers-find-no-evidence-of-in-game-covid-19-transmission-for-sec-2020-football-season/