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Friday, August 28, 2020

Lipocine under pressure on extended timeline for FDA review of Tlando application

The FDA has informed Lipocine (NASDAQ:LPCN) that it needs more time to complete its review of the company’s marketing application for oral testosterone replacement therapy Tlando (testosterone undecanoate). The agency’s action date was today.

Management says the FDA did not provide a new action date but stated that the review should wind up in the coming weeks. It did not request additional data.

Nothing has been easy for the company in its registration efforts. It received a third Complete Response Letter (CRL) in November 2019 after previous CRLs in June 2016 and May 2018.


GoodRx Holdings readies $100M IPO

GoodRx Holdings (GDRX) has filed a prospectus for a $100M IPO.

The Santa Monica, CA-based company has developed a platform aimed at helping consumers find lower prescription drug prices based on data gathered from more than 70K U.S. pharmacies. It experienced 15M monthly visitors last quarter. The company boasts that it is the most downloaded medical app in the Apple and Google Play App Stores.

Since consumers use the app for free, the company makes money by taking a cut of the cost each prescription, mostly from pharmacy benefit managers (PBMs). Almost all of the prescription volume is generated through brick and mortar pharmacies.

2020 Financials (6 mo.): Revenue: $256.7M (+48%); Net Income: $54.7M (+75%); Non-GAAP EBITDA: $101.2M (+36%); Cash Flow Ops: $83.8M (+67%).


Covid pandemic growth rate may be obscured due to changes in testing rates

Scientists have reviewed reported cases and testing data of COVID-19 and have determined that changes in the testing rate may be masking the true growth rate and extent of the pandemic.

For epidemics and pandemics such as COVID-19, the response from public health organizations depends on the number of people infected and the rate of increase in infection. Due to the limited number of tests, predicting the actual extent of the pandemic based on available testing capacity is very important. However, as time passes, the testing capacity increases and testing standards improve, changing previous predictions about the growth and spread of the pandemic.

In the current work, a team of three scientists, including Ryosuke Omori from Hokkaido University, reviewed data collected from Italy, Japan, and California, U.S., to determine the effect of changes in the testing rates during the COVID-19 pandemic. Their analysis, published in the International Journal of Infectious Diseases in April, shows that the testing rates need to be standardized across the entire period of the pandemic in order to reflect its actual growth rate.

The data for the cumulative number of COVID-19 cases were obtained from governmental and international databases. The period covered was between February 15 and March 11 for Japan and Italy, and between March 1 and March 21 for California. This data was statistically analyzed. In Italy, the increase in cases was exponential for the entire time period. In Japan, the increase was linear until March 5, and exponential thereafter. In California, there were no cases reported until March 9, but the increase was exponential once cases were reported.

The scientists investigated why a switch between linear and exponential growth in the cumulative number of cases was observed in Japan. They were able to correlate this switch with a rapid increase in the testing rate that occurred between March 3 and March 4. They suggest that the linear increase in the number of cases prior to March 5 does not reflect the true growth of the pandemic but is an effect of saturated testing capacity and preferential testing for highly suspicious samples. The four-fold increase in testing rate revealed the true extent and spread of the pandemic in Japan.

“The bias created by changes in testing rates has public health implications,” says Omori. “Our work indicates that including data on the testing strategy and ascertainment bias will help to model the growth and spread of the pandemic more accurately.”

Associate Professor Omori, from the Research Center for Zoonoses Control at Hokkaido University, specializes in epidemiological modeling: the use of mathematics and statistics to understand and predict the spread of diseases. Since the outbreak of COVID-19, he has turned his efforts to ascertaining the true extent of the spread of the pandemic in Japan and abroad.




More information: Ryosuke Omori et al. Changes in testing rates could mask the novel coronavirus disease (COVID-19) growth rate, International Journal of Infectious Diseases (2020). DOI: 10.1016/j.ijid.2020.04.021


Brickell Biotech rallies; initiated BUY at Lake Street

Lake Street Capital initiated Brickell Biotech (BBI +17.2%) with a Buy rating and price target of $6 indicating more than five-folds increase from current levels.

Analyst Thomas Flaten believes that the company has rapidly advanced its lead development program to Phase 3 readiness since becoming public via a reverse merger in 2019.

He further adds that he likes the odds of Brickell’s treatment of primary axillary hyperhidrosis taking on Eli Lilly’s Qbrexza in serving an underappreciated and under-treated disease state affecting a population of ~10M in the U.S.

Investor Presentation of Brickell states that it expects to  initiate pivotal Phase 3 program in Q4; also there is a significant U.S. market opportunity in Hyperhidrosis which affects ~ 4.8% (15.3M) of U.S. population.


Fauci Wasn’t in Meeting About New CDC Testing Guidelines: CNN

A key member of the White House Coronavirus Task Force wasn’t in the meeting that decided on the updated CDC guidelines that say people without COVID-19 symptoms may not need to get tested.

Anthony Fauci, MD, the director of the National Institute of Allergy and Infectious Diseases, said he was undergoing surgery and not in the August 20 task force meeting.

“I was under general anesthesia in the operating room and was not part of any discussion or deliberation regarding the new testing recommendations,” he told CNN.

On Monday, the CDC updated the testing recommendations on its website. According to the change, people who have been in close contact with someone who has COVID-19 may not need to be tested if they don’t have symptoms. Previously, the website said that testing was recommended for everyone who has close contact with someone who has COVID-19.

“I am concerned about the interpretation of these recommendations and worried it will give people the incorrect assumption that asymptomatic spread is not of great concern,” Fauci said. “In fact, it is.”

On Wednesday, reporters asked Admiral Brett Giroir, the COVID-19 testing coordinator, whether the new guidelines were approved by the task force. He said that “all the docs signed off on this,” even before it moved to the task force level, according to CNN.

Public health officials have criticized the update and said the change could discourage testing among asymptomatic people who are spreading the virus. The new guidelines also surprised some federal health officials who are typically briefed on coronavirus updates, CNN reported.

“It’s coming from the top down,” one federal health official told CNN, saying that the CDC was pressured to change the guidance.

Later on Wednesday, both Giroir and CDC Director Robert Redfield issued statements to CNN with the exact same phrasing— that the “updated guidelines were coordinated in conjunction with the White House Coronavirus Task Force, received appropriate attention, consultation and input from task force experts.”

In addition, Redfield said that anyone who has been in close contact with someone who has COVID-19 should monitor their symptoms, wear a mask, follow social distancing guidelines and ask their doctor whether a test is necessary.

“Everyone who wants a test does not necessarily need a test. The key is to engage the needed public health community in the decision with the appropriate follow-up action,” he told CNN. “Testing may be considered for all close contacts of confirmed or probable COVID-19 patients.”

SOURCES:

CNN, “Fauci says he was in surgery when task force discussed CDC testing guidelines.”

CDC, “Overview of Testing for SARS-CoV-2 (COVID-19).”

CNN, “CDC was pressured ‘from the top down’ to change coronavirus testing guidance, official says.”


Brookline and Chardan bullish on Forte Biosciences

Brookline’s has initiated coverage on Forte Biosciences (FBRX +13.9%) with a Buy rating and a price target of $90 (~200% upside). Sees a favorable risk-reward for its lead asset FB-401 in inflammatory skin diseases.

Chardan also upgraded the stock to Buy from Neutral with a $45 price target (~50% upside). The analyst estimates $892.5M in risk-adjusted 2030 sales for the drug candidate. He is positive on “potentially best-in-class approach” for FB-401 in atopic dermatitis, compared to other microbiome medicines (based on their clinical trials).

Recently, Truist initiated coverage on the company with Buy rating and price target of $70.


More Evidence Points to Kids Being COVID-19 ‘Silent Spreaders’

Children with COVID-19 may shed the virus for up to three weeks, even when asymptomatic, according to a study from South Korea.

Among 91 children with confirmed COVID-19 infection, SARS-CoV-2 RNA was detected in nasopharyngeal and oropharyngeal swabs for a mean 17.6 days after an initial positive test, reported Jong-Hyun Kim, MD, PhD, of The Catholic University of Korea, in Seoul.

About half of children with symptoms continued to shed the virus for three weeks, including 49% of children with upper respiratory tract infections and 55% of children with lower respiratory tract infections, they wrote in JAMA Pediatrics.

Of 20 asymptomatic children in the cohort, SARS-CoV-2 RNA was detected for a mean 14.1 days after the initial positive test, and 4 (20%) were still shedding the virus at 3 weeks.

Notably, this study involved PCR tests, and the detection of SARS-CoV-2 using this method may not equate to infectivity, the authors noted.

“The major hurdle implicated in this study in diagnosing and treating children with COVID-19 is that a considerable number of children are asymptomatic, and even if symptoms are present, they are unrecognized and overlooked before COVID-19 is diagnosed,” Kim and co-authors wrote.

Although most COVID-19 cases tend to be less severe in children than adults, the role children play in transmission is not yet clear. With many school districts resuming in-person schooling next month, a renewed attention has been placed on how children spread the virus. In adults, an estimated 20%-45% of infections are asymptomatic.

Younger children with COVID-19 have been shown to carry greater amounts of SARS-CoV-2 in their upper respiratory tract than adults, indicating they could be important drivers of viral spread.

However, it’s unclear whether a high viral load correlates with disease severity or longer periods of shedding in children, commented Roberta L. DeBiasi, MD, MS, and Meghan Delaney, DO, MPH, both of Children’s National Hospital in Washington, D.C., in an accompanying editorial.

Regardless, it has been suspected that the low number of cases originally reported in children was not because they weren’t getting infected, but because they were asymptomatic or had mild cases and were not getting tested, commented Thomas A. Russo, MD, of the University of Buffalo, who was not involved in this research.

“With kids going back to school, if they do get infected and bring it back to the house, it is going to increase cases,” Russo told MedPage Today. “Just because kids come back from school feeling great, doesn’t mean they aren’t going to spread the virus.”

Kim and colleagues estimated that 93% of infections in children would have been missed if only symptomatic cases were tested. Symptomatic children experienced symptoms a median of 3 days prior to being diagnosed, but this varied widely (1 to 28 days), and only 7% of children tested positive concurrently with the onset of symptoms, Kim and co-authors reported.

“A surveillance strategy that tests only symptomatic children will fail to identify children who are silently shedding virus while moving about their community and schools,” DeBiasi and Delaney wrote.

Earlier this week, the CDC changed its COVID-19 testing guidelines to now state that non-vulnerable, asymptomatic close contacts of infected individuals “do not necessarily need a test” unless a provider or local health authorities recommend it.

In contrast, the public health response in South Korea allows for expansive testing, contact tracing, and isolation; children who come into contact with a confirmed or suspected COVID case are quarantined in healthcare facilities.

The current study involved a cohort of children who tested positive while under observation, and were tested at median 3-day intervals. The cohort — median age 11, 58% boys — were most commonly infected through a household contact (63%), followed by infections imported from travel (17%), cluster-associated transmission (12%), by another contact outside their social circle (4%), or an unknown route (4%). Three children had asthma and three had epilepsy, but no other comorbid conditions or immunodeficiencies were reported.

The most common symptoms experienced by children were fever (69%), respiratory symptoms (60%), gastrointestinal symptoms (18%), and loss of smell or taste (16%). Just 12 children received treatment, most commonly with lopinavir-ritonavir (Kaletra) or hydroxychloroquine, and none required mechanical ventilation.

Median duration of symptoms was 13 days, but this also varied widely, with some kids having symptoms for 5 weeks. Among kids who were presymptomatic at the time of diagnosis, symptom duration was a median 3.5 days, while those who had just developed symptoms at diagnosis experienced symptoms for a median 6.5 days; symptoms lasted a median 13 days in children who were symptomatic before diagnosis.

There was no significant difference in duration of symptoms between children with upper respiratory tract infections and those with mild or moderate lower respiratory tract infections.

The latter finding “suggests that even mild and moderately affected children remain symptomatic for long periods of time,” DeBiasi and Delaney wrote.

The study had all of the limitations of available testing. Some patients may test negative on one platform and positive on the next, and sampling at different locations within the respiratory tract or even by different staff can influence whether a test comes back positive, DeBiasi and Delaney noted.

SARS-CoV-2 has also been detected in other bodily fluids, including stool, for prolonged periods, which were not measured in this study.

Disclosures

Neither the authors nor the editorialists reported any ties with industry.

Primary Source

JAMA Pediatrics


Secondary Source

JAMA Pediatrics