Gilead’s remdesivir first to gain FDA approval for COVID-19 patients.

The US Food and Drug Administration approved remdesivir (Veklury) on Thursday for treating hospitalized Covid-19 patients, a first for the disease that started a global pandemic. Remdesivir, an antiviral that works by limiting SARS-CoV-2 replication, is indicated for hospitalized patients age 12 and up (and at least 40 kg [88.2 lbs]).

Previously, the intravenous drug was solely available under an emergency use authorization (EUA) from the agency, according to MedPage Today. The FDA also announced a new EUA for remdesivir in hospitalized kids age 12 and older weighing at least 3.5 kg (7.7 lbs) but less than 40 kg, and in kids under age 12 weighing at least 3.5 kg. The news comes exactly a week after a major international trial led by the World Health Organization (WHO) found no survival improvement for hospitalized COVID-19 patients treated with the drug, and no improvement in time to recovery.

Approval was based on three randomized trials, including the National Institutes of Health-led ACTT-1 Trial, a Phase 3 trial that showed that patients with mild, moderate, and severe disease who were treated with up to 10 days of remdesivir recovered a median 5 days quicker than those on placebo, and a median 7 days quicker in those requiring oxygen at baseline. Fewer patients on oxygen at baseline progressed to mechanical ventilation or extracorporeal membrane oxygenation with remdesivir (13% vs. 23%), and a trend toward lower day-29 mortality was observed with the drug (11.4% vs. 15.2%).

“The approval of Veklury marks an important milestone in efforts to help address the pandemic by offering an effective treatment that helps patients recover faster and, in turn, helps preserve scarce healthcare resources,” ACTT-1 investigator Barry Zingman, MD, of the Albert Einstein College of Medicine and Montefiore Medical Center in New York City, said in a press release from drugmaker Gilead Sciences Inc. (Foster City CA).

“The availability of a rigorously tested treatment that can significantly speed recovery and offers other benefits such as lower rates of progression to mechanical ventilation, provides hospitalized patients and their families important hope and offers healthcare providers a critical tool as they care for patients in need,” added Dr. Zingman.

“Today’s approval is supported by data from multiple clinical trials that the agency has rigorously assessed and represents an important scientific milestone in the COVID-19 pandemic,” said FDA Commissioner Stephen Hahn, MD, in the agency’s announcement.

Other trials that supported approval showed that a 5-day course of the drug was roughly equivalent to a 10-day course, and that some clinical benefit was also seen in patients hospitalized with moderate illness.

Remdesivir is contraindicated in those allergic to the drug or any of its components.

Separately, according to Johns Hopkins Medical, as of Saturday, October 24, there were nearly 42.4 million COVID-19 global cases confirmed, and some 1.1 million deaths. Confirmed cases in the US totaled 8.5 million with over 224,000 deaths. Both of the US figures comprise 20% of the global totals.

COVID-19 Addenda: The US on Friday set a single-day record for COVID-19 cases during a harrowing new surge. This disturbing third surge, which led to a US single-day record of more than 85,000 new cases Friday, is happening less than two weeks from Election Day, which will mark the end of a campaign dominated by the pandemic and President Trump’s much-criticized response to it.

As of Friday evening, 15 states had added more cases in the past week than in any other seven-day stretch of the pandemic: Wisconsin, a battleground in the presidential election, Colorado, Kentucky, Illinois, Wyoming, Idaho, Utah, South Dakota, Montana, Arkansas, Alaska, Tennessee, Ohio, Indiana and North Dakota. And four states added more deaths last week than in previous weeks: Wisconsin, Kentucky, South Dakota and Oklahoma. North Dakota leads the nation in coronavirus cases per capita. Illinois is averaging more than 4,100 new cases per day, up 85% from the average two weeks ago. And Pennsylvania, another battleground state, on Friday reported a record of 2,258 cases.

Elsewhere, AstraZeneca PLC (London) announced on Friday that the Food and Drug Administration has allowed the company to restart its Phase 3 COVID-19 vaccine trial in the US. The company has said the FDA has reviewed all data and concluded that it is safe to resume the trial. It expects results from its trials later this year. The Wall Street Journal first reported the approval on Friday.

“The restart of clinical trials across the world is great news as it allows us to continue our efforts to develop this vaccine to help defeat this terrible pandemic,” AstraZeneca CEO Pascal Soriot said in a statement. “We should be reassured by the care taken by independent regulators to protect the public and ensure the vaccine is safe before it is approved for use.”

The news came just days after a volunteer who was a part of the trial in Brazil died. Reuters reported on Wednesday that Brazil’s health regulatory Anvisa said the trial would still continue. Reuters cited a Brazilian news outlet that reported the volunteer was part of the placebo group, and did not receive the actual vaccine.

Also on Friday, Johnson & Johnson (New Brunswick NJ) announced that it is preparing to restart its trial following consultation with the FDA. The company became the second to pause its trial earlier this month after a person suffered an “unexplained illness.”  The company said that no clear cause of the incident was identified following review by an independent safety committee, and that there was “no evidence that the vaccine caused the event.” J&J said preparations to resume the trial in the US are now underway, and that “discussions with other regulators around the world to resume the clinical trial program are progressing.” The Washington Post first reported the approval. The Post, citing anonymous people familiar with the trial, reported that the committee examined medical data from the event, and safety data from 100,000 people who received vaccines that use the same technology.

And US health officials redefined what counts as “close contact” with someone with COVID-19 to include briefer but repeated encounters. For months, the Centers for Disease Control and Prevention said close contact meant spending a solid 15 minutes within 6 feet of someone who tested positive for coronavirus. Last Wednesday, the CDC changed it to a total of 15 minutes or more–so shorter but repeated contacts that add up to 15 minutes over a 24-hour period now count.

The CDC advises anyone who has been in close contact with a COVID-19 patient to quarantine for two weeks. The change may prompt health departments to do contact tracing in cases where an exposure might previously have been considered too brief, said Dr. William Schaffner, a Vanderbilt University infectious diseases expert. It also serves notice that the coronavirus can spread more easily than many people realize, he added.

Fauci suggests a national mask mandate as infections in US spiral; warns the general public might not get a COVID-19 vaccine until mid-2021.

Dr. Anthony S. Fauci, the nation’s top infectious disease expert, said on Friday that the country should consider implementing a first-ever national mandate requiring masks, to help control a surge in coronavirus cases across the US that has become the most severe to date. Fauci also gave an update on a possible COVID-19 vaccine on Friday, telling MSNBC he thinks the general public might not get it until mid-2021.

In addition, he confirmed reports that President Donald Trump has not attended a coronavirus task force meeting in months. Appearing on CNN, Dr. Fauci said that enforcing a mask mandate would be difficult. But with conditions worsening across disparate regions of the country, he said he could be inclined to recommend the dramatic measure.

“There’s going to be a difficulty enforcing it,” he said, “but if everyone agrees that this is something that’s important and they mandate it and everybody pulls together and say, you know, we’re going to mandate it but let’s just do it, I think that would be a great idea to have everybody do it uniformly.”

Most states have imposed mask requirements to varying degrees, covering different spheres–such as indoor and outdoor spaces–at some point during the pandemic. However, a minority of states, including Iowa, have resisted issuing directives on masks even as case counts have begun to climb to new highs. And even states and cities that have more restrictive orders in place tend to allow some exceptions, such as when people are exercising.

The White House has obstructed federal efforts that would have mandated masks in a more limited way, blocking an order drafted by the Centers for Disease Control and Prevention last month that would have required masks on public transportation. But with more than a dozen states reporting more cases over the past week than in any other seven-day stretch during the pandemic, Dr. Fauci said that it may be necessary to have a more coordinated, national approach.

“I get the argument saying, ‘Well if you mandate a mask, then you’re going to have to enforce it and that’ll create more of a problem,’” Fauci said. “Well, if people are not wearing masks then maybe we should be mandating it.” (Ref: The New York Times)

COVID-19 vaccine standards questioned at FDA advisory meeting.

COVID-19 vaccine safety, dueling efficacy standards, and representation of groups from racial and ethnic minorities to children drew focus Thursday at arguably the most watched FDA advisory committee meeting ever. The FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) featured a brief appearance by Peter Marks, MD, PhD, director of the agency’s Center for Biologics Evaluation and Research, who called this, “an exceptionally well-attended advisory committee meeting.”

In addition to the FDA’s website, the meeting was broadcast on YouTube, with over 15,000 views when it concluded in the early evening says MedPage Today. FDA’s director of the Office of Vaccines Research and Review, Marion Gruber, PhD, set the tone in her opening remarks: “I want to take a moment to reassure the American public…today’s discussions will provide transparency about the data we will request and evaluate,” she said. “Vaccine development can be expedited, but…it cannot and must not be rushed.”

But safety was foremost on the minds of committee members, who expressed concern that median 2 months of safety data required by the FDA seemed “arbitrary.” Some worried that if products receive emergency use authorization (EUA), blinding in their Phase 3 trials would be immediately broken and placebo controls stopped, instead of allowing them to continue for vital additional data collection. FDA staff said the 2-months mark was chosen because most vaccine adverse events occur within the first 6 weeks.

A presentation by the Reagan-Udall Foundation for the Food and Drug Administration–a nonprofit established by Congress to advance the agency’s overall mission–shared results from “listening sessions” on vaccine hesitancy. These indicated that the public harbors concerns about the speed of the process, as well as distrust of government and the healthcare system. Some committee members seemed to share their skepticism. Members of the public are “probably not going to have an appetite for anything short of the rigorous process we’re used to seeing,” said Hayley Altman-Gans, MD, of Stanford University Medical Center.

Archana Chatterjee, MD, of Rosalind Franklin University in North Chicago, said that she thought safety needed to be the top priority, even before effectiveness. “Whatever products are put on the market under whatever mechanism” should be safe, she said. “Then you get to effectiveness.”

However, efficacy standards received plenty of attention, too. A presentation by Hilary Marston, MD, of the National Institutes of Health, argued for a primary efficacy endpoint of at least 60%. FDA guidance, however, stated a goal of 50%.

“We are really trying to strike a balance between getting information on the most significant clinical outcomes and…being able to make an impact on the pandemic in a reasonable amount of time based on good data,” said Doran Fink, MD, PhD, of FDA’s Office of Vaccines Research and Review.

Fink fielded a number of questions from committee members about the FDA’s vaccine standards, including why vaccine manufacturers were allowed to use relatively broad definitions of COVID-19 in their primary endpoint. Some panelists thought it should be severe disease as opposed to any evidence of COVID-19.

IPO Sector: Included among recent SEC filings for initial public offerings, Vallon Pharmaceuticals Inc., a biopharmaceutical company developing abuse-deterrent prescription drugs for CNS disorders, registered up to $17 million worth of common stock. The company’s clinical-stage product currently under development is Abuse-Deterrent Amphetamine Immediate-Release, or ADAIR, a proprietary, abuse-deterrent oral formulation of immediate-release (short-acting) dextroamphetamine for the treatment of attention-deficit/hyperactivity disorder, or ADHD, and narcolepsy. ADAIR has completed a Phase 1 pivotal bioequivalence study and a Phase 1 food effect study. The Philadelphia, PA-based company was founded in 2018. The company has not selected a listing exchange or ticker yet. ThinkEquity is the sole bookrunner on the deal. No pricing terms were disclosed.

Elsewhere Sotera Health Inc., which provides lab services to the medical device and pharma industries, registered up to $100 million worth of common in an IPO. However, this is likely a placeholder for a deal we estimate could raise up to $750 million. Sotera Health is a leading global provider of mission-critical sterilization and lab testing and advisory services to the medical device and pharmaceutical industries. It has more than 5,800 customers in over 50 countries, which include more than 40 of the top 50 medical device companies and 8 of the top 10 global pharmaceutical companies by revenue. The company operates 63 facilities worldwide. The Broadview Heights, OH-based company was founded in 1946 and booked $790 million in revenue for the 12 months ended June 30, 2020. It plans to list on the Nasdaq under the symbol “SHC.” J.P. Morgan and Credit Suisse are among the joint bookrunners on the deal. No pricing terms were disclosed.

Foghorn Therapeutics Inc., a preclinical biotech developing gene therapies for hematologic cancers and solid tumors, raised $120 million by offering 7.5 million shares at $16, within the range of $15 to $17. At pricing, the company commands a Fully Diluted Market value of $628 million. Foghorn is developing a new class of medicines targeting genetically determined dependencies within the chromatin regulatory system through its proprietary Gene Traffic Control platform. The company’s two most advanced candidates are FHD-286, a selective allosteric ATPase inhibitor, and FHD-609, a protein degrader. The candidates are being developed for hematologic cancers and solid tumors, and the company plans to file INDs for FHD-286 and FHD-609 in the 4Q20 and 1H21, respectively. The Cambridge, MA-based company was founded in 2015 and lists on the Nasdaq under the symbol “FHTX.” Goldman Sachs, Morgan Stanley, Cowen and Wedbush PacGrow acted as joint bookrunners on the deal. Shares closed the week up 13% at $18.12.

Eucrates Biomedical Acquisition Inc., a blank check company formed by Vedanta Management targeting data-driven healthcare and biotech businesses, raised $100 million by offering 10 million units at $10. Each unit consists of one share of common stock and one-third of a warrant, exercisable at $11.50. The company is led by Chairman Stelios Papadopoulos, who is the Chairman of Biogen, Exelixis, and Regulus Therapeutics. The SPAC plans to target North American and European healthcare companies, specifically those utilizing biomedicine and data science. Eucrates Biomedical Acquisition lists on the Nasdaq under the symbol “EUCRU.” Stifel and H.C. Wainwright acted as joint bookrunners on the deal. Shares closed the week unchanged at $10.

Abcam PLC, which sells biological reagents and tools for research, drug discovery, and diagnostics, raised $157 million by offering 8.9 million ADSs at $17.50, below the as-converted last close of $18.06 for its shares trading on the AIM (ABC). At pricing, the company raised 6% more in proceeds than anticipated and commands a fully diluted market value of $4.0 billion. Abcam identifies, develops, and distributes reagents and tools for life science research. Its product offerings include a portfolio of antibodies and related protein research tools. Its customers are primarily scientists and researchers in academic institutions, research institutes, and pharmaceutical, biotechnology, and diagnostics companies. The Cambridge, UK-based company was founded in 1998 and booked $335 million in revenue for the 12 months ended June 30, 2020. Abcam lists on the Nasdaq under the symbol “ABCM.” Morgan Stanley, BofA Securities and SVB Leerink acted as joint bookrunners on the deal. Shares closed the week up 8% to $18.90.

G Medical Innovations Holdings, which provides app-connected medical devices for monitoring vital signs, launched its IPO on Thursday. It had previously filed for a US IPO in May 2019 but withdrew the following August. The Rehovot, Israel-based company plans to raise $30 million by offering 5 million shares at a price range of $5 to $7. At the midpoint of the proposed range, G Medical would command a fully diluted market value of $362 million. The early commercial stage company is developing mobile health (mHealth) and telemedicine solutions and monitoring service platforms. Its current product offerings include the Prizma medical device, a clinical grade device used to transform smartphones into medical monitoring devices, and Extended Holter Patch System, a multi-channel patient-worn biosensor that captures electrocardiogram data continuously for up to 14 days. G Medical was founded in 2014 and booked $5 million in revenue for the 12 months ended June 30, 2020. It plans to list on the Nasdaq under the symbol “GMVD.” Boustead Securities and Fosun Hani Securities are the joint bookrunners on the deal. It is expected to price this week.

Galecto Biotech AB, a Phase 2 biotech developing therapeutics for fibrosis and related diseases, announced terms for its IPO on Thursday. The Copenhagen, Denmark-based company plans to raise $85 million by offering 5.7 million shares at a price range of $14 to $16. At the midpoint of the proposed range, Galecto would command a fully diluted market value of $395 million. Galecto’s initial focus is on the development of small-molecule inhibitors of galectin-3 and lysyl oxidase-like 2, which play key roles in regulating fibrosis. Its lead product candidate, GB0139, is an inhaled inhibitor of galectin-3 for the treatment of severe fibrotic lung diseases such as idiopathic pulmonary fibrosis (IPF). The company has conducted a Phase 2a trial in 24 IPF patients and has initiated a Phase 2b trial in 450 IPF patients, with topline results expected in 2022. Galecto was founded in 2011 and plans to list on the Nasdaq under the symbol “GLTO.” BofA Securities, SVB Leerink, and Credit Suisse are the joint bookrunners on the deal. It is expected to price this week.

And Compass Therapeutics Inc., a Phase 1 immuno-oncology biotech developing novel protein and antibody therapies, registered up to $50 million in an IPO. The company previously filed in August 2020 for a $261 million secondary offering, with intent to list on the “OTCQB.” The company’s lead candidate, CTX-471, is a monoclonal antibody agonist of CD137, a key co-stimulatory receptor on immune cells. Preclinical studies showed that CTX-471 as a monotherapy led to a complete eradication of large tumors in mice. The company initiated a Phase 1 trial in July 2019 in a subset of oncology patients previously treated with PD-1 or PD-L1 immune checkpoint inhibitors, with the Part 2 cohort expansion portion expected to be completed by the 2H21. Compass plans to initiate a Phase 2/3 trial by early 2022. The Cambridge, MA-based company was founded in 2014 and plans to list on the Nasdaq under the symbol “CMPX.” Citi, Credit Suisse, and Stifel are the joint bookrunners on the deal. No pricing terms were disclosed.