Top Stories for the Week of November 16, 2020

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Pfizer, BioNTech’s COVID-19 vaccine shockingly effective in trials, but will effectiveness and safety hold up after widespread distribution?

Pfizer Inc. (NYC) and partner BioNTech SE’s (Mainz DEU) highly effectual COVID-19 vaccine prospect caught Wall Street and the medical community by surprise last week, yet the same experts who are ecstatic over the news signaled that the effectiveness of the vaccine will likely be lower in the real world. The companies, which in March teamed up to develop a coronavirus vaccine, said last Monday that an interim analysis from the Phase 3 clinical trial indicates BNT162b2, their investigational mRNA vaccine, has an efficacy rate that is higher than 90%. The study’s protocol calls for an efficacy rate of 60%, according to MarketWatch.

“Given everything the world is going through and being humble enough to admit there’s a lot we are still learning about this virus, it was still a relief to see,” Raymond James analyst Steve Seedhouse said. But clinical trials are also conducted in controlled clinical settings that aren’t likely to be replicated in the real world. “In the clinical trial, you select the patients that you like, and you follow them very closely,” said Mizuho Securities analyst Difei Yang. “In the real world, there’s all kinds of ages, and everyone has different underlying health conditions.”

In studies like the ones being conducted for the COVID-19 vaccines, factors could include anything from how a vaccine is stored and handled by medical professionals to the types of people who volunteer to participate in a clinical study, who may be more likely to socially distance and wear a mask, especially if it’s unclear whether they received the investigational vaccine or the placebo.

“When you put [a vaccine] out in the real world, people may behave differently,” said Dr. Paul Offit, director of the Vaccine Education Center at Children’s Hospital of Philadelphia. “They think, ‘Great. I’m good. The vaccine works. It’s 90% effective. I can take off my mask.’”

In addition, the data shared by BioNTech and Pfizer were gathered approximately two months after trial participants received the second and final dose of the vaccine candidate. There are still questions about how long immunity to the virus lasts, either by natural infection or vaccination, and differing lengths of durability could impact the effectiveness of a vaccine.

“As the vaccine is adopted in the real world, if durability of effectiveness wanes over months, then you would start to see a reduction of that 90% number over time,” Seedhouse wrote. “But while we don’t know a lot about [the] durability of immunity yet, the general lack of widespread reinfection a year or so into this pandemic suggests durability might be good enough to retain such a high efficacy even in the real world.”

There is still no detailed information about how the vaccine performed in different vulnerable patient populations, including the elderly and those with co-morbidities such as diabetes or hypertension that may make them more susceptible to infection and more severe forms of the disease. Pfizer closed the week up 6% at $38.62, while BioNTech’s ADRs surged 15% to $106 in New York.

Separately, according to Johns Hopkins Medical, as of Saturday, November 14, there were 53.7 million COVID-19 global cases confirmed, and some 1.31 million deaths. Confirmed cases in the US totaled over 10.8 million with nearly 245,000 deaths. The US figures comprise 20.19% and 18.7% respectively of the global totals. The US population comprises 4% of the global total.

COVID-19 Addenda: Dr. Anthony Fauci, the top US infectious disease expert, said he has had no contact with President-elect Joe Biden’s coronavirus transition team and sees no reason to quit to join that effort when there is so much to do now to fight the surging pandemic.

“I stay in my lane. I’m not a politician. I do public health things,” he said in an interview on Thursday ahead of this week’s Reuters Total Health conference.

Since January, Fauci has served on President Donald Trump’s White House Coronavirus Task Force, a position that has frequently put him at odds with the president, who has sought to downplay the pandemic and focused instead on opening the economy.

“There’s absolutely no reason and no sense at all for me to stop doing something in the middle of a pandemic that is playing a major role in helping us get out of the pandemic,” Fauci said. His advice for the president-elect, he said, is “exactly the same” as what he is recommending now–social distancing, avoiding crowds, wearing masks, washing hands. “Public health principles don’t change from one month to another or from one administration to another.”

Elsewhere, in a large international study of patients admitted to the intensive care unit (ICU) with COVID-19, the likelihood of having severe pneumonia (i.e., needing invasive mechanical ventilation) increased stepwise with increasing body mass index (BMI)–independent of diabetes, hypertension, dyslipidemia, or current smoking. The main finding, reported by Medscape, was a linear correlation between BMI and need for invasive mechanical ventilation, after adjustment for center, age, sex, and other prespecified metabolic risk factors. Risk was “highest for older people and males, but the next most important risk factor to developing severe pneumonia if infected [was] obesity,” said François Pattou, MD, Centre Hospitalier Universitaire de Lille, France. The results were also recently published in a preprint article in The Lancet.

“The high number of patients included here [allowed us] to disentangle the role of various metabolic cofactors and to show that obesity, not diabetes or hypertension, was the main determinant of severe pneumonia [after age and gender],” Pattou told Medscape.

And the impact of obesity was most pronounced in women younger than 50.

US states, cities, and hospitals are scrambling to buy ultra-cold freezers that can safely store Pfizer Inc.’s (NYC)  COVID-19 vaccine, ignoring advice from the US Centers for Disease Control and Prevention (CDC) to hold off. The push, reported by Reuters, reveals a lack of infrastructure to support a super cold vaccine campaign, including equipment to store millions of doses of Pfizer’s vaccine at temperatures of minus 70 degrees Celsius (minus 94°F), significantly below the standard for vaccines of 2-8 degrees Celsius (36-46°F).

Some specialty freezer makers warn of months-long waits for units. It also marks widespread wariness of the advice from the CDC, which on Aug. 26 urged healthcare providers not to purchase ultra-low temperature (ULT) freezers, saying it was working on solutions for Pfizer’s “very complex storage and handling requirements.” A CDC spokeswoman on Thursday said the agency expects the first vaccine doses will be in limited quantities and rapidly deployed, reducing the need to store them in specialized freezers.

And German biotech CureVac AG (Tübingen) said its experimental COVID-19 vaccine has been shown to remain stable at 5 degrees Celsius (41°F) for at least three months, making it potentially easier to distribute than some rivals’ compounds. CureVac, which is close to launching Phase 3 testing of its vaccine, said the stability of the liquid vaccine was tested at its anticipated storage concentration, and it has been stored at 5 degrees Celsius as well as below minus 60 degrees.

Tests also established stability at room temperature for up to 24 hours. Last week, Pfizer Inc. (NYC) and BioNTech SE (Mainz DEU) were the first to release data showing that their vaccine worked in a large, Phase 3 clinical trial. However, their vaccine needs to be stored at minus 70 degrees Celsius. Before it is administered, it can be kept in a fridge for up to five days, or in thermal shipping boxes for up to 15 days. CureVac is using the so-called messenger RNA (mRNA) approach for its vaccine, the same as the BioNTech-Pfizer alliance and Moderna Inc. CureVac shares closed the week up 49% at $75.20 in New York.

Moderna could start evaluating COVID-19 vaccine data “within days,” says Fauci.

Moderna Inc. (Cambridge MA) has finished accumulating data for a first analysis of its COVID-19 vaccine and expects to have an announcement on the vaccine’s effectiveness by the end of the month, the company said in a statement last Wednesday. Affirming this timing, Anthony Fauci, the top US infectious disease expert, said anywhere between “a couple of days” to “a little more than a week.” A high degree of effectiveness for the vaccine would make sense as it was “almost identical” to the Pfizer Inc. (NYC) shot, Fauci said at a conference organized by the Financial Times.

Pfizer last Monday announced that its coronavirus vaccine is over 90% effective. Moderna is conducting a clinical trial of 30,000 participants, with half receiving the vaccine and half receiving a placebo, which is a shot of saline that does nothing, says CNN. In order for Moderna’s vaccine to be considered for authorization by the US Food and Drug Administration, at least 53 study participants needed to become ill with COVID-19. The trial hit that 53 mark Wednesday, but Moderna doesn’t know if the participants who became ill received the vaccine or the placebo.

The company is now preparing data to send to the trial’s Data and Safety Monitoring Board, an independent panel of experts. That board will look to see how many of the participants who became ill received the vaccine and how many received the placebo. If a statistically significant number received the placebo, that means the vaccine is effective against the virus. Moderna thinks the board will share efficacy results before the end of the month. And, since cases are rapidly rising in the US, more than 53 participants will become ill with COVID-19 by the time the announcement is made. Moderna and Pfizer use messenger RNA for their vaccines. Fauci has said Pfizer’s promising outcomes are good news for Moderna, too.

“Moderna has an almost identical mRNA,” Fauci told the Financial Times. “We hope we’re going to see a similar kind of result from Moderna. If we do, then we’ll have two vaccines in play.”

Pfizer’s results from the never-before-approved mRNA technology were better than expected, said Fauci, director of the National Institute of Allergy and Infectious Diseases.

“I really quite honestly did not expect that we would have a result as striking as this–more than 90%, close to 95% efficacy–on the first vaccine that went through the gate,” he said.

Moderna is working with NIAID to develop its vaccine.

Government preps for unique challenge of Eli Lilly antibody rollout as efficacy questions remain.

The Infectious Diseases Society of America (IDSA) on Thursday said it is evaluating the data on which US regulators approved emergency use of Eli Lilly & Co.’s (Indianapolis) COVID-19 antibody drug, and noted that more information is needed. The medical association, which represents more than 12,000 specialists, said its guidelines panel is evaluating available trial data and will issue its recommendations soon.

The Food and Drug Administration last Monday authorized Lilly’s bamlanivimab for people over age 65 recently diagnosed with mild-to-moderate COVID-19, and for patients age 12 and older who have an underlying risk factor for serious illness, such as obesity or diabetes. The agency said the drug should not be used in hospitalized patients.

“It is important for clinicians and members of the public to be aware that the available data are limited, and that more information is needed to determine the effect of this therapy on clinically meaningful outcomes,” the IDSA said in a statement.

The association has updated its COVID-19 treatment guidelines several times over the course of the pandemic, adding drugs like Gilead Sciences Inc.’s (Foster City CA) antiviral remdesivir and generic steroids as trial data have emerged. It does not always follow the lead of the FDA, which in August authorized emergency use of plasma derived from COVID-19 survivors for treating patients hospitalized with the illness. The IDSA still advises that convalescent plasma only be used in the context of a clinical trial.

“For new therapeutics to be used widely and routinely outside of clinical trials, we urge that there be sufficient safety and efficacy data to be confident regarding their use,” the group said.

The IDSA said it is also concerned about the limited supply of the Lilly antibody treatment. The Department of Health and Human Services said it has purchased 300,000 doses of the drug and will begin distributing them free-of-charge this week to state health departments. (Ref: Reuters)

Medical Stock Spotlight:

Clinical-stage biotech Five Prime Therapeutics Inc. (NASDAQ:FPRX) led advancing issues, skyrocketing 328% over the week to $21.41 in response to positive midstage trial results for the stomach cancer drug candidate bemarituzumab. Specifically, Five Prime and Shanghai-based partner Zai Lab Ltd. reported that the combination of bemarituzumab and mFOLFOX6 chemotherapy beat out placebo plus mFOLFOX6 on three efficacy endpoints–median progression-free survival, median overall survival, and overall response rate–in patients with fibroblast growth factor receptor 2b-positive, HER2-negative front-line advanced gastric or gastroesophageal junction cancer. Zai Lab owns the drug’s developmental and commercial rights within China through a licensing deal with South San Francisco-based Five Prime. Bemarituzumab will likely still have to pass muster in a larger pivotal stage trial to gain approval in either China or the US. But a first-line stomach cancer drug represents an enormous commercial potential. Stomach cancer is one of the most common types of malignancy as well as a leading cause of death across the globe.

Elsewhere, Urovant Sciences Inc. (NASDAQ:UROV) soared 98% to $16.02. The huge gain came after the Irvine, CA-based company announced that it has entered into a definitive agreement to be acquired by Sumitovant Biopharma Ltd. for $584 million. Sumitovant was already Urovant’s largest shareholder, owning around 72% of the company. Urovant CEO James Robinson said his company has “been partnering closely with [Sumitovant] on plans to efficiently launch vibegron and achieve scale as quickly as possible.” Vibegron is Urovant’s lead pipeline candidate that’s in late-stage testing for potentially treating overactive bladder. The transaction price represents a 96% premium over Urovant’s closing share price prior to news of the deal. Pierre Legault, the lead independent member of Urovant Sciences’ board of directors, said “Sumitovant’s offer represents exceptional value for shareholders.” Urovant’s shareholders must first approve the acquisition. The deal is expected to close in the first quarter of 2021. The FDA is scheduled to make its decision for vibegron by Dec. 26, 2020.

And Aptevo Therapeutics Inc. (NASDAQ:APVO) surged 90% to $44.98. The clinical-stage biotechnology company focused on developing novel immuno-oncology therapeutics based on its proprietary ADAPTIR platform provided an update on its ongoing APVO436 Phase 1 clinical trial. APVO436 is a novel anti-CD123 x anti-CD3 targeted investigational bispecific antibody therapy being evaluated for the treatment of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), in a Phase 1/1b open-label, dose-escalation study evaluating the safety and pharmacokinetic profile. On Friday, November 6, Seattle-based Aptevo received preliminary data regarding cohort 6, which indicated complete remission in a second patient, in addition to the one previously announced. In total, there are now two patients with clinical remission in cohort 6. The data received also showed one patient exhibiting stable disease status, and six patients where the disease had progressed. A total of nine patients were listed in cohort 6 of the clinical trial.

But clinical-stage biopharma Cassava Sciences Inc. (NASDAQ:SAVA) plummeted 28% to $7.08. The drugmaker’s shares sank following the announcement of an underwritten public offering. While the details of the offering have yet to be released, Cassava said that the funds would be used to finance a late-stage trial of its Alzheimer’s disease drug candidate sumifilam, along with general corporate purposes. A preliminary prospectus supplement laying out the all-important details should be available soon. Shareholders rarely take kindly to public offerings. In this case, however, Edmonton, CAN-based Cassava may be doing shareholders a real favor. Put simply, the company simply didn’t have the funds to advance sumifilam into a late-stage trial. In the most recent quarter, for example, Cassava revealed that it was down to a measly $24.1 million in cash and cash equivalents. A pivotal stage-trial for an Alzheimer’s disease drug, by contrast, can easily cost hundreds of millions. Shareholders, for their part, were probably hoping for a licensing deal or a straight up buyout in lieu of a capital raise.

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