Nymox on track to file fexapotide applications in ~four months

Thinly traded micro cap Nymox Pharmaceutical Corp. (NYMX +8.3%) perks up on almost double normal volume, albeit on turnover of only 264K shares, on the heels of its announcement that its lead fexapotide program in benign prostatic hyperplasia (enlarged prostate) is on track despite COVID-19 disruptions.

It expects to file marketing applications in late Q3/early Q4.

Fexapotide triflutate (NX-1207) is a pro-apoptotic (promotes cell death) protein administered directly into the prostate via a transrectal injection that does not require anesthesia or sedation.

https://seekingalpha.com/news/3584613-nymoxplus-8-on-track-to-file-fexapotide-applications-in-four-months

Patent loss on MS hit Tecfidera pressures Biogen to score win in Alzheimer’s

Now that the worst-case scenario for Biogen in its Tecfidera patent battle with Mylan has come to pass, Wall Street analysts have a warning for investors: New generic competition to the multiple sclerosis drug will put extraordinary pressure on Biogen to win FDA approval of its Alzheimer’s drug aducanumab.
Yesterday a West Virginia federal court invalidated a key patent on Tecfidera, opening the door for challenger Mylan to introduce a generic version of the MS drug as early as this year—eight years earlier than low-priced competition to the $4-billion-a-year blockbuster was expected to arrive.
Biogen said in a statement that it will appeal the decision.

Nevertheless, Mylan could launch its generic “at risk,” before the appeals court rules. What’s more, there’s a separate Tecfidera patent battle playing out in Delaware, brought by more than 20 generic drugmakers, and that judge could “bring in the West Virginia judgment,” warned SVBLeerink analysts in a note to investors.
The West Virginia judgment prompted SVBLeerink to lower its 2021 revenue estimate for Biogen from $13.9 billion to $13.1 billion and its earnings per share forecast from $33.30 to $29.80. Similar downgrades from other Wall Street firms sent shares of Biogen down more than 7% in after-hours trading to $260.30.

It’s not just the generic threat that’s putting pressure on Biogen’s MS franchise, analysts say. Biogen did win FDA approval for its follow-up drug, Vumerity, late last year, but it hasn’t had much luck converting doctors to the new option. “Specifically, while docs report a high degree of familiarity with the drug, and even acknowledge its tolerability advantage, conversion has been thin, garnering just 1.3% patient share so far,” said Piper Sandler analysts in a note.
Meanwhile, Roche’s Ocrevus is rapidly stealing market share from both Tecfidera and Vumerity. Ocrevus hit blockbuster status in its first year on the market, making it one of the most successful drug launches of the last two years. Novartis is also proving to be a tough competitor with Mayzent, and now it’s gunning for even more of the MS market with ofatumumab, its once-monthly at-home injection.
Therefore, regardless of the timing of the Tecfidera generic, “the winds of competitive change in the MS market do not favor Biogen,” Piper Sandler analysts said.

Could aducanumab make up for an early loss of Tecfidera sales? That’s a long shot, too. Biogen surprised investors last fall when it declared that an earlier futility analysis came to the wrong conclusion and that it would, in fact, pursue FDA approval of the Alzheimer’s drug. Now the company is plotting a third-quarter filing to the FDA, and it’s getting a Swiss manufacturing site outfitted to manufacture the drug starting next year.
“Clearly what happens on the Alzheimer’s front will be the main driver of shares in the near term,” said J.P. Morgan analysts in a note to investors. “How that plays out is one big unknown.”
A quicker fix for Biogen would be to acquire a company with one or more near-term pipeline prospects. CEO Michel Vounatsos said during Biogen’s first-quarter earnings call that the company has the “financial flexibility and capacity to evaluate potential external business development and M&A opportunities” and that it remains “active” in that area.
But Biogen is clearly not quite as active in M&A as analysts would hope, particularly with the new patent threat to Tecfidera. Said J.P. Morgan, “we remain perplexed by the lack of meaningful business development/M&A activity from Biogen.”
https://www.fiercepharma.com/pharma/patent-loss-ms-hit-tecfidera-puts-pressure-biogen-to-score-a-win-alzheimer-s-analysts

RTW Investments acquires 9.95% stakes in Celldex Therapeutics

June 19, 2020

RTW Investments discloses 9.95% passive stakes in Celldex Therapeutics (CLDX +11.2%) representing 1.88M shares.

See Form 13G

https://seekingalpha.com/news/3584596-rtw-investments-acquires-9_95-stakes-in-celldex-therapeutics

Glenmark gets India approval for favipiravir as COVID-19 treatment

Glenmark Pharmaceuticals Ltd has received Indian regulatory approval to make and sell oral antiviral drug favipiravir for treating mild-to-moderate COVID-19 infections in the country, it said on Friday.
The Mumbai-based company said the approval was part of India’s accelerated approval process and the drug was meant for “restricted emergency use,” meaning patients must sign their consent before being treated by the drug.
Favipiravir is also undergoing trials in other countries to test its efficacy as a COVID-19 treatment.
Japan’s Fujifilm Holdings Corp, which makes favipiravir under the brand name Avigan, said last week its research on the drug as a potential COVID-19 treatment may drag on until July.

Drugmakers across the world have been rushing to develop a treatment or vaccine for the novel coronavirus, which has infected 8.5 million people globally, killing more than 453,000, according to a Reuters tally.
India, the fourth-worst hit country, reported a record daily jump in the number of coronavirus cases on Friday, and the death toll reached 12,573.
The approval for favipiravir in India, which Glenmark plans to sell as “FabiFlu”, was granted based on “evaluation of data,” the company said in a brief statement to stock exchanges. (bit.ly/310MByO)

The company plans to provide more details in a press briefing on Saturday, it added.
Glenmark began a late-stage trial of favipiravir on COVID-19 patients last month. It is also separately testing a combination of favipiravir and umifenovir, another anti-viral drug, as a potential COVID-19 treatment.
https://www.reuters.com/article/us-health-coronavirus-glenmark-pharms/glenmark-gets-india-approval-for-favipiravir-as-covid-19-treatment-idUSKBN23Q2E9

Chinese vaccine may not be ready for sale until at least 2021

A coronavirus vaccine candidate China is developing may not be ready for sale until at least 2021, as researchers struggle to move into large-scale human trials in the country because of a lack of new infections, a senior company executive said.
More than 10 experimental vaccines are being tested in humans globally as scientists race to protect against the novel coronavirus that has killed more than 450,000 people.
But none of them has yet passed late-stage phase 3 trials that require thousands of participants to determine a vaccine candidate’s effectiveness.
China, where the virus first originated last year, saw less than 10 new local cases reported daily on average in May, making it less favorable for a late-stage clinical trial.

“We hope we can launch more international cooperations and conduct a multiple-center phase 3 clinical study to help bring the vaccine to the market,” China National Biotec Group’s (CNBG) vice president Zhang Yutao told state media China News Service.
“The vaccine won’t be on the market until at least next year based on current plans,” he said in the interview broadcast late on Thursday.
A new outbreak in the capital Beijing city last week has infected more than 180 people, but Yang said the number of new patients compared with the population was still too low to make it an ideal trial site.

CNBG is an affiliate of state-backed China National Pharmaceutical Group (Sinopharm). One of the two experimental vaccines developed by its units showed some positive signs in early stage human trials.
State media reported last week that China was offering its two vaccine candidates to employees at state-owned firms traveling overseas.
https://www.reuters.com/article/us-health-coronavirus-china-sale/chinese-vaccine-may-not-be-ready-for-sale-until-at-least-2021-state-media-idUSKBN23Q2AZ

U.S. hospitals in hard hit regions step up use of steroids on sickest Covid patients

Several U.S. hospitals in states with fresh surges of COVID-19 cases have started treating their sickest patients with dexamethasone rather than await confirmation of preliminary results of a study by British researchers, who said the inexpensive steroid saves lives.

The move illustrates how the pandemic is changing the way hospitals work, at least regarding COVID-19 patients.
Traditionally, doctors wait for detailed data to be published in a peer reviewed journal – or for guidelines from medical societies – before embracing a new treatment, so they can better gauge the risks against the drug’s benefits. The urgency of the coronavirus pandemic and lack of other treatments has altered those calculations.
Dexamethasone is the first drug shown to lower the risk of death in severely ill COVID-19 patients in what researchers running the trial hailed as a “major breakthrough.”
The Oxford University researchers said in a news release that dexamethasone reduced death rates by around a third among COVID-19 patients requiring mechanical breathing assistance or oxygen. Britain’s health ministry has already approved its use in the state-run health service.

“It almost feels unethical not to use the drug,” said Dr. Kartik Cherabuddi, an infectious diseases specialist at the University of Florida’s (UF) medical school.
UF’s Gainesville hospital updated its COVID-19 treatment guidelines as of Tuesday to include using dexamethasone. It previously used the extremely cheap generic medicine sparingly for those patients.
Cherabuddi noted that his hospital – and many others – similarly started treating COVID-19 patients with Gilead Science’s (GILD.O) antiviral drug remdesivir based on data from a news release.
That drug, which unlike dexamethasone was not yet approved by regulators for any other conditions, shortened hospital recovery times in a clinical trial. It did not have an effect on mortality.
Several hospital systems, including New York’s Northwell Health and the University of Washington (UW) had not been using steroids on COVID-19 patients. There was some concern it could lead to worse outcomes because it suppresses the immune system.

“For us, the case numbers are low and so there is not much pressure to do something new,” said UW’s Dr. Mark Wurfel, who is eager to see the final data. Places like Florida and Oklahoma, where COVID-19 hospitalizations are rising, are under more pressure, he said.
“The urgency of having hundreds, maybe thousands of very sick COVID patients in hospitals and ICUs changes the calculus. Many lives could be saved if the trial results are real,” Wurfel added.
AdventHealth, which has nearly 50 hospitals in nine states, has been using dexamethasone for COVID-19 patients on ventilators with success since early April, said Eduardo Oliveira, executive medical director for critical care for AdventHealth’s central Florida region.
At its eight hospitals in the Orlando area, Oliveira said the mortality rate for patients requiring ventilators was about 26%, “lower than almost every other reported mortality in the literature right now.”
He noted it was difficult to know whether that success was due to the use of steroids.
After reviewing the British study release and trial protocols, Advent expanded its dexamethasone use to also include patients receiving supportive oxygen but not on ventilators.

Dr. Brent Brown, medical director of University of Oklahoma’s intensive care unit, said his hospital added the steroid to its treatment guidelines for patients in the ICU this week. Oklahoma is one of several U.S. states with rapidly rising coronavirus cases.
“We changed our practice completely. It was kind of an about face,” he said. “But we’re delighted to have something that looks so promising.”
https://www.reuters.com/article/us-health-coronavirus-usa-dexamethasone/u-s-hospitals-in-hard-hit-regions-step-up-use-of-steroids-on-sickest-covid-19-patients-idUSKBN23Q1MN

What Minnesota’s Protests Are Revealing About Covid-19 Spread

In the weeks since George Floyd was killed by Minneapolis police officers outside a grocery store at 38th Street and Chicago Avenue, the intersection has remained closed to traffic—filled instead with flowers, memorial murals, and thousands of daily visitors who come to pay their respects. Except for the masks when you’re inside that now-sacred space, it’s hard to remember there’s a pandemic going on. But in the shadow of the Sabathani Community Center a few blocks to the west, where a transformation of another kind has been underway, it’s impossible to forget.

On Tuesdays and Wednesdays, one corner of the parking lot now fills with a maze of air-conditioned tents and about a dozen nurses wearing hairnets, gowns, and face shields. From 11 o’clock in the morning until 6 in the evening, they work their way through a steady line of cars carrying people eager to have a swab inserted deep into their nasal cavities—not necessarily because they think they are coming down with Covid-19 but because they’ve recently been around lots of other people.

As Floyd’s death sparked a massive protest movement that spread from Minneapolis to the rest of the world, epidemiologists and public health officials fretted that the thronging crowds would supercharge viral spread, driving deadly new surges in coronavirus infections. In an effort to prevent that from happening, officials in many metro areas, including Minneapolis and St. Paul, rushed to stand up free testing near protest sites. The testing program in the Twin Cities has been particularly well-embraced, making it a sort of testbed for the rest of the nation, where protests began later. Now, early data from Minnesota’s efforts suggests such fears may have been overblown. In the vast, unplanned experiment of unleashing tens of thousands of previously isolated people into a few city blocks, that’s good news. But perhaps even more significant is how this preliminary testing data is starting to reshape scientists’ understanding of how the novel pathogen behaves, with important implications for states’ plans to reopen.
The state of Covid-19 testing in the US has improved since a disastrous initial rollout, with about 500,000 tests performed daily now, compared to just a few thousand in mid-March. But fierce competition for lab testing supplies and a lack of federal coordination in obtaining and distributing them has meant that the US has been unable to mobilize mass testing efforts like those that succeeded in Singapore, South Korea, and Taiwan.

That’s forced states to prioritize. Until the protests erupted during the last week of May, Minnesota had only been testing people with symptoms of the respiratory disease, except at hospitals and long-term care facilities, where about 80 percent of the state’s Covid-19 related deaths have occurred. Following the protests, the Minnesota Department of Health changed the criteria for the state’s still-limited supply of tests to include people who’d participated in mass gatherings within the previous week. “We made an exception because of the extensiveness of those events,” says Kristen Ehresmann, the Minnesota Department of Health director of infectious disease.
The decision paved the way for opening four free testing sites around the Twin Cities, in neighborhoods most affected by the protests and subsequent violence. Public health officials are encouraging anyone who’s recently attended a protest, vigil, or neighborhood event to get tested there, regardless or whether or not they have symptoms of Covid-19. The revamped criteria also allows people who’ve recently been at protests and other community events to obtain tests through their doctors. Now, results from the first week of testing are in. And at least among the people who volunteered for the earliest rounds of tests, the data suggests that the mass gatherings may not result in a spike of Covid-19 infections after all.

Of the 3,200 people tested so far at the four popup sites across the metro, 1.8 percent have tested positive for Covid-19, says Ehresmann. HealthPartners, one of the largest health care providers in Minnesota, also reported to the state that it had tested about 8,500 people who indicated that attendance at a mass gathering was the reason they wanted a test. Among them, 0.99 percent tested positive. These numbers have been one of the few pleasant surprises since the outbreak began, says Ehresmann. “Right now, with the data available to us, it appears there was very little transmission at protest events,” she says. “We’re just absolutely relieved.”
In a handful of other US cities that have rolled out free testing for protest-goers, the first round of results look similarly encouraging. In Seattle, fewer than 1 percent of the 3,000 people tested after attending protests were positive for coronavirus, according to a statement put out by the city’s mayor last Friday. This week, Boston officials announced that 14 out of 1,288 people tested so far were positive for coronavirus, or 1.1 percent. Of course, these are only three cities out of hundreds that have been enveloped in large-scale protests against police brutality and institutionalized racism. Many are not conducting widespread public testing, and so signals of protest-related spikes may take longer to emerge. Additionally, the peak of protests in some cities, like New York City, San Francisco, and Washington, DC, arrived several days after actions in Minneapolis, where the response to Floyd’s death was swift and furious.
Still, these early numbers are welcome news to Roger Shapiro, a professor of immunology and infectious diseases at Harvard’s T.H. Chan School of Public Health. “When I hear a 1 percent positivity rate, that’s encouraging to me that these protests are not representing new hot spots,” he says. That’s because 1 percent is around the background level of community transmission that might be expected if one were to test a large sample of randomly selected people.
Though Shapiro supports the protests, he was worried about their potential to seed new chains of infection. So why didn’t they? His hunch is that two things protected protesters against disease transmission more than some scientists expected: wearing masks and being outdoors. “I think we would have seen a very different situation with fewer masks and indoor events,” says Shapiro.
Whether SARS-CoV-2 spreads primarily through larger respiratory droplets caused by coughing and sneezing, smaller aerosols expelled during breathing and talking, or via fomites left on surfaces is still an area of active scientific debate. It’s one that is hampered by the fact that there are no simple methods for detecting the amount of viral particles in the air. But analyses of patterns of spread in China and aboard the Diamond Princess cruise ship have provided evidence that airborne transmission likely plays an important role.
In order for SARS-CoV-2 to establish an infection inside someone’s lungs, that person must breathe in a sufficient number of viral particles. This “minimum infectious dose” is still unknown for SARS-CoV-2, but researchers suspect it is low. A number of factors can influence the likelihood you’ll be exposed to an infectious dose should you happen to be around someone who is currently infected. They include (but are not limited to) how much virus they’re shedding into the air, how far away from them you are, how quickly the air around you is moving, how quickly you’re breathing, and how long you’re near them. Basically, it boils down to the concentration of viral particles floating around in the vicinity right around your nose and mouth.

Masks work by reducing the number of infectious viral particles exhaled into the environment. They are not a substitute for social distancing and hand-washing, but the collective evidence makes a strong case for wearing them during a pandemic. Even homemade masks can have a significant effect. A recent study conducted by researchers at the Argonne National Laboratory found that the filtering efficiency of different materials used in homemade masks is similar to that of medical masks. This finding refutes an earlier study conducted in South Korea, which was influential during the early days of the pandemic and was later retracted for faulty methodology.
At protests in Minneapolis, the vast majority of demonstrators have been wearing masks. The state health department distributed 50,000 masks to community organizations to make available to participants. So it’s tempting to see the city’s low coronavirus prevalence in protesters as one of the more robust mask success stories to date in the US. But according to experts, it’s difficult to isolate the effect of mask-wearing from the state’s protester testing data alone. Linsey Marr, a professor of environmental engineering at Virginia Tech and leading expert in the airborne transmission of viruses who has become a trusted advisor to the World Health Organization during the current crisis, says that though there is increasing evidence that masks help reduce the transmission of SARS-CoV-2, the outdoor environment also likely plays a large role.
“Outdoors there is so much dilution in the atmosphere that it would be unusual for virus levels to build up in the air,” she wrote WIRED in an email. That dilution happens in two ways. Air flow whisks away droplets and aerosols immediately. During the daytime, ultraviolet radiation from sunlight also inactivates any viral particles carried inside them, a process that takes a few minutes. (And wouldn’t factor into transmission dynamics at night, when many protests took place.) Even so, “you would have to be extremely close to someone else for a long time to be exposed significantly,” wrote Marr.
Shapiro says there may be another reason why the Minnesota protest-goers’ infection rate is low so far: It could still be too early to detect an increase in infections. Though most people develop symptoms within five to seven days, the incubation period can be as long as two weeks. The majority of people who do develop symptoms can manage them at home for the first 10 days. But for a subset of people whose immune systems either can’t control the virus or instead have an overblown response, that 10-day mark is when they get sick enough to go to the hospital. “We’re just about approaching that time when I’d expect to see hospitalizations increase,” he says.
At least in Minnesota, daily Covid-19 hospitalizations have been steadily going down since the protests began, according to data from the state department of health. Overall, the seven-day average of new infections has also been on the decline in the last two weeks, even as testing has increased. That suggests that low positivity rates among protest-goers is consistent with statewide trends. And that’s notable, because the people who turn up voluntarily for a state-sponsored medical test are unlikely to be a random segment of the population: This sample may be biased toward people without obvious symptoms and away from people suspicious of the government.
Still, Ehresmann says it’s important to remember that Minnesota was the first to experience massive demonstrations, which makes the state a sort of forerunner, and not necessarily predictive of what other states might observe. In scores of other cities that hosted major protests, public health officials are still collecting data. “It’s going to be really important to look across the country at this data in aggregate to see what we can learn collectively about infections following these events,” says Ehresmann. For now, she agrees it’s simply too early to draw any sweeping conclusions.
There is the possibility, she says, that in states that are experiencing upswings in coronavirus circulation, protesters might test positive at higher rates because there was a bigger pool of potentially sick people who didn’t yet know they were infected. As of Thursday, Covid-19 cases were climbing in 20 states, particularly in the American Sun Belt and the West, according to The New York Times. Arizona, Florida, Nevada, Oregon, and Texas all reported their largest one-day spikes in new cases this week.

Epidemiologists point to a rush to reopen businesses that put people into close contact indoors as the main driver behind these new surges. However, it’s difficult to disentangle the effects of official policy from human behavior. What people actually do matters a lot more than what the regulations say they should do.
In many parts of the country, mask-wearing has become intensely politicized, so much so that Texas governor Greg Abbott recently signed an executive order stripping local governments of the power to require people to wear masks in public. Arizona’s governor, Doug Ducey, also tried to block the state’s mayors from mandating mask-wearing, but backtracked this week after many of them made an appeal on national television. In Oklahoma, one mayor tried to make masks mandatory for anyone entering an indoor place of business. But the order lasted only hours. It was amended after business employees and city officials received a deluge of verbal abuse and threats of physical violence.
On Saturday, President Donald Trump is moving forward with plans to hold his first rally since the pandemic started, in Tulsa, Oklahoma. Notably, this large-scale event will be hosted indoors—at a 20,000 person arena—with attendees required to wear masks, receive temperature checks at the door, and sign a waiver absolving the Trump campaign of coronavirus-related lawsuits. Tulsa health officials are urging the campaign to cancel the event or at least move it outdoors.
If it goes forward as planned, and participants wear their masks the whole time, and mask-wearing alone is not enough to block the spread of transmission indoors, the results could be disastrous. But it would also provide another natural experiment. While the George Floyd protests are teaching scientists about outdoor spaces, the Trump rally may offer important data points about the riskiness of indoor spaces. Of course, collecting that data will depend on how many rally attendees later get tested. Because counter to what the president of the United States says, if the US stops testing right now, it doesn’t actually mean the virus goes away. It just means scientists and policymakers won’t know how bad it really is.
https://www.wired.com/story/what-minnesotas-protests-are-revealing-about-covid-19-spread/