Can Gilead make remdesivir pay?

Gilead has been rewarded handsomely, via share price gains, for its Covid-19 remdesivir work, but the potential costs should not be forgotten.

Remdesivir is out of the gate for Gilead, with emergency use authorisation from the FDA permitting a commercial rollout of the antiviral for Covid-19. Instead, the company has pledged to donate its entire supply of 1.5 million doses, which will be distributed by the US government.
Gilead is expected to profit at some point, however: how else to explain the 23% share price surge this year, adding $18bn to the group’s market cap? This implies that a huge commercial opportunity awaits, which feels premature when considering that so much remains unknown.
On the company’s earnings call last week executives said they were still unsure what any future commercial model for remdesivir might look like. But big money is at stake here: Remdesivir costs could reach $1bn this year, Gilead estimates.
“We have to have a sustainable economic model that works here, and that achieves access [and] affordability to patients around the world,” chief executive Daniel O’Day said. “But rest assured, we understand our responsibility.”
Unsurprisingly the company will not talk about price yet – aside from the political sensitivities of this topic, remdesivir’s real benefit is far from clear (Remdesivir results pile up, but what do they all mean?, April 30, 2020). The cost-watchdog Icer has had a stab at this topic, however, putting together models based on “cost recovery” and a traditional cost-effectiveness analysis.
They concluded that a price of $10 per 10-day dose would cover manufacturing costs – although this would require Gilead to write off its R&D investment. But a price of up to $4,500 could be considered cost-effective, Icer found, assuming a mortality benefit is confirmed and using a $50,000 quality-adjusted life year threshold.
Few in the sellside have published remdesivir models yet, but this upper price seems to be higher than many are assuming. Consensus from EvaluatePharma provides some insight; however, this average is derived from some wildly different numbers, demonstrating the lack of clarity around this opportunity.

Gilead has a fiduciary duty to its shareholders, which means that executives will be focused on recovering its remdesivir costs. But the risk that this might not happen cannot be ignored.
More effective treatments might emerge, or vaccines could lessen the need for remdesivir more quickly than expected. And of course there is the opportunity cost of Gilead not focusing on potentially more profitable activities.
Analysts at Baird noted that the commercial opportunity remains “ambiguous”, and are sceptical that this will be substantially more than a “goodwill enterprise” for the company. Considering that $1bn could be sunk in remdesivir this year alone, this is a pretty big slice of goodwill.
Gilead should be applauded for its efforts to find a treatment for the pandemic. And while talking about commercial models will not win it fans, calls for greater clarity from investors will soon grow louder.
https://www.evaluate.com/vantage/articles/analysis/vantage-views/can-gilead-make-remdesivir-pay

Gilead off intraday lows on WHO interest in wider use of remdesivir

Gilead Sciences (GILD +0.1%) has rebounded off session lows, albeit on below-average volume, on the heels of reports that the World Health Organization (WHO) plans to seek talks with the company about wider use of remdesivir in COVID-19.

The FDA gave its emergency use nod on Friday, May 1, the first antiviral approved for the respiratory infection anywhere in the world.

https://seekingalpha.com/news/3568445-gilead-off-intraday-lows-on-who-interest-in-wider-use-of-remdesivir

Unique new mutation found in coronavirus study

As the coronavirus pandemic has swept across the U.S., in addition to tracking the number of COVID daily cases, there is a worldwide scientific community engaged in tracking the SARS-CoV-2 virus itself.

Efrem Lim leads a team at ASU that looks at how the virus may be spreading, mutating and adapting over time.
To trace the trail of the virus worldwide, Lim’s team is using a new technology called next-generation sequencing at ASU’s Genomics Facility, to rapidly read through all 30,000 chemical letters of the SARS-CoV-2 genetic code, called a genome.
Each sequence is deposited into a worldwide gene bank, run by a nonprofit scientific organization called GISAID. To date, over 16,000 SARS-CoV-2 sequences have been deposited GISAID’s EpiCoVTM Database. The sequence data shows that SARS-CoV-2 originated a single source from Wuhan, China, while many of the first Arizona cases analyzed showed travel from Europe as the most likely source.
Now, using a pool of 382 nasal swab samples obtained from possible COVID-19 cases in Arizona, Lim’s team has identified a SARS-CoV-2 mutation that had never been found before—where 81 of the letters have vanished, permanently deleted from the genome.
The study was published in the online version of the Journal of Virology.
Lim says as soon as he made the manuscript data available on a preprint server medRxiv, it has attracted worldwide interest from the scientific community, including the World Health Organization.
“One of the reasons why this mutation is of interest is because it mirrors a large deletion that arose in the 2003 SARS outbreak,” said Lim, an assistant professor at ASU’s Biodesign Institute. During the middle and late phases of the SARS epidemic, SARS-CoV accumulated mutations that attenuated the virus. Scientists believe that a weakened virus that causes less severe disease may have a selective advantage if it is able to spread efficiently through populations by people who are infected unknowingly.
Teasing apart what exactly this means is of profound interest to Lim and his colleagues. The ASU research team includes LaRinda A. Holland, Emily A. Kaelin, Rabia Maqsood, Bereket Estifanos, Lily I. Wu, Arvind Varsani, Rolf U. Halden, Brenda G. Hogue and Matthew Scotch.
The ASU virology team had been setup to perform research on seasonal flu viruses, but when the 3rd case of COVID-19 was found in an Arizona individual on January 26, 2020, they knew they had all technical and scientific prowess to rapidly pivot to examining the spread of SARS-CoV-2.
“This was the scientific opportunity of a lifetime for ASU to be able to contribute to understand how this virus is spreading in our community,” said Lim. “As a team, we knew we could make a significant difference.”
All the positive cases show that the SARS-CoV-2 viral genomes were different from each other, meaning they were independent from each other. This indicates that the new cases were not linked to the first Arizona case in January, but the result of recent travel from different locations.
In the case of the 81-base pair mutation, because it has never been found before in the GISAID database, it could also provide a clue into how the virus makes people sick. It could also form a new starting point for other scientists to develop antiviral drugs or formulate new vaccines.
SARS-CoV-2 makes accessory proteins that help it infect its human host, replicate and eventually spread from person to person. The genome deletion removes 27 protein building blocks, called amino acids, from the SARS-CoV-2 accessory protein ORF7a. The protein is very similar to the 2003 SARS-CoV immune antagonist ORF7a/X4.
The ASU team is now hard at work performing further experiments to understand the functional consequences of the viral mutation. The viral protein is thought to help SARS-CoV-2 evade human defenses, eventually killing the cell. This frees up the virus to infect other cells in a cascading chain reaction that can quickly cause the virus to make copies of itself throughout the body, eventually causing the serious COVID-19 symptoms 8-14 days after the initial infection.
Lim points out that only 16,000 SARS-CoV-2 genomes have been sequenced to date, which is less than 0.5% of the strains circulating. There are currently more than 3.5 million confirmed COVID-19 cases worldwide.
Lim’s group has teamed up with TGen, UA and Northern Arizona University to continue tracking different genetic strains of the new coronavirus. Together, the newly formed Arizona COVID-19 Genomics Union (ACGU) hopes to use big data analysis and genetic mapping to give Arizona health care providers and public policy makers an edge in fighting the growing pandemic.

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Infection researchers identify starting points for SARS-CoV-2 vaccine and therapy development

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More information: LaRinda A. Holland et al, An 81 nucleotide deletion in SARS-CoV-2 ORF7a identified from sentinel surveillance in Arizona (Jan-Mar 2020), Journal of Virology (2020). DOI: 10.1128/JVI.00711-20

https://medicalxpress.com/news/2020-05-scientific-team-unique-mutation-coronavirus.html

Walmart seen generating 9% Q1 U.S. comp

Credit Suisse says it remains constructive on Outperform-rated Walmart (WMT -0.2%) as the retailer’s Q1 earnings report approaches.

Analyst Seth Sigman: “We raise our comps estimates for 1H, although we lower EPS to reflect incremental margin pressures/ cost headwinds/ FX. Based on our work, we are more confident in sales outlook past Q1 (incl the potential for comps to reaccelerate from the recent Apr. trend), while we also believe that WMT will be better positioned to navigate what could be very choppy consumer waters ahead, and benefit med/long-term from significant share gains from the structural changes in shopping behavior we are seeing.”

Sigman forecasts Q1 U.S. comparables sales will be up 9.3% vs. +5.5% prior forecast and +3.5% consensus. He also says Walmart is just starting to see a benefit from government stimulus.

https://seekingalpha.com/news/3568414-walmart-seen-generating-9-q1-u-s-comp

Routine cancer screenings have plummeted during the pandemic

As it became clear in March that the coronavirus was tearing through the U.S., federal health officials and cancer societies urged Americans to delay their routine mammograms and colonoscopies. The public has heeded those recommendations — and that’s helped lead to an apocalyptic drop in cancer screenings, according to a white paper released Monday by the electronic medical records vendor Epic.
Appointments for screenings for cancers of the cervix, colon, and breast were down between 86% and 94% in March, compared to average volumes in the three years before the first Covid-19 case was confirmed in the U.S., the Epic data show.
The paper provides only a snapshot of the overall picture — the company’s records cover just a fraction of all cancer screenings — but they help reveal the magnitude of the gaps in care resulting from the pandemic. Although there is debate about whether certain preventive cancer screenings actually save lives, many researchers fear that deadly cancers could go undetected if screening appointments that would have normally happened in recent weeks are not soon rescheduled.

Epic

The data suggest there is reason to be concerned that cancer screenings may not rebound even as some states begin to reopen their economies. The Epic researchers found an elevated rate of cancellations of cancer screening appointments even in the days before mid-March, when counties began issuing stay-at-home orders and the American Cancer Society and the Centers for Disease Control and Prevention recommended that people delay non-urgent outpatient care.
“We’re also fairly convinced that even once they lift the lockdowns, we’ll still see the concerned patients a little bit more reluctant to go in,” Epic President Carl Dvorak told STAT. “Truthfully, it doesn’t take much to talk a person out of going in for a colonoscopy.”

Epic looked at data from 2.7 million patients in the U.S. whose records showed that they had at least one screening for cervical, breast, or colon cancer between 2017 and 2019. The data cover 190 hospitals spread across 39 health systems in 23 states.
Although there’s always seasonal variability in how many people go in for cancer screenings — appointments generally spike after Breast Cancer Awareness Month in October — the Epic researchers found that the plunge during the pandemic period went well beyond what could be expected under normal variation.
Breast and cervical cancer screenings fell by 94% in March compared to the 2017-2019 averages, while colon cancer screenings dropped by 86%, the researchers found. Dvorak, who commissioned the research, said he was “shocked” by the scale of that drop-off.
The Epic numbers follow a similar data release last week from the San Francisco-based health tech company Komodo Health, which analyzed the billing records of 320 million patients in the U.S. Komodo found that screening for cervical cancer was down 68% from March 19 to April 20, compared to the previous 11 weeks and a comparable period last year. Tests for cholesterol, diabetes, and active and recurrent cancers were down, too, with the sharpest declines in Covid-19 hotspots like New York and Massachusetts.
Cancer screenings generally take place at doctor’s offices and at diagnostic centers run by larger health systems. There’s been variability in how these facilities have responded to the pandemic: Some have closed their doors altogether, while others have stayed open for emergencies or maintained a skeleton crew of staff.

Epic did not draw any conclusions in its research about why a small fraction of screenings continued in recent weeks, Dvorak said. It’s possible, though, that some of those may have represented people who were especially worried about their cancer risk, such as a woman who found a large lump in her breast, or people who were less concerned about getting infected with the virus by going into the clinic.
As doctor’s offices and health systems begin to go back to relatively normal operations, Dvorak said he hopes that the research can help Epic’s customers develop a strategy for booking people who may have delayed recommended cancer screenings, such as by prioritizing calls to people at high risk of cancer due to past irregular screenings or a family history.
Epic doesn’t have any immediate plans to try to publish its findings on a preprint server or in a medical journal, but Dvorak said the company hopes to partner with its health system customers so they can do research on health outcomes associated with Epic’s data.
Dvorak said his team also plans to mine Epic’s data to see if it substantiates anecdotes that the company has been hearing from its customers, such as reports that brain surgeries have declined or that there’ve been more emergency amputations for people with diabetes.

Routine cancer screenings have plummeted during the pandemic, medical records data show

Collateral damage occurs when doctors and patients wear ‘Covid-19 blinders’

My friend Mina had a stroke at home while an infectious disease pandemic raged around her. As a physician, I was blindsided. Not just by her stroke, but by the collateral damage of this pandemic: delayed diagnosis and treatment for severe medical illnesses at the cost of trying to prevent exposure to the virus that causes Covid-19.
Part of the problem is seeing everything through a coronavirus lens. There are catastrophic risks when doctors and patients wear Covid-19 blinders.
Mina is at high risk for developing complications from Covid-19 because she is 70 years old and has multiple sclerosis and heart disease. One day her left leg suddenly became weak and she fell twice. Alarmed, she phoned her neurologist, who told her that her multiple sclerosis was likely becoming more symptomatic.

Normally, symptoms like sudden weakness in a leg or arm would be evaluated in a doctor’s office or emergency department with a physical exam and brain MRI to see if they were due to a stroke or seizure. Mina’s medical center, however, had recently reported new Covid-19 cases. To avoid exposing her to the virus, her neurologist advised her to stay home and to monitor her symptoms.

Two days later she developed difficulty speaking and smiling on one side of her face. With the new symptoms and another call to her neurologist, we all agreed that she needed an MRI.

It revealed that Mina had experienced a stroke. Instead of getting treatment right away, which is the standard of care for stroke — “time is brain” stroke specialists often say — it was only days later that she received the vital medications, referrals to physical and speech therapy, and evaluations of her neck and brain.
There are widespread reports of fewer visits in emergency departments and doctors’ offices for strokes, heart attacks, and routine medical care. Across the U.S., 911 calls have fallen by 20% to 35%. Spain has seen a nearly 40% reduction in emergency procedures for heart attacks during the Covid-19 crisis. Outside of emergency care, overall outpatient visits for routine medical conditions are down by 30%, including virtual visits. And in a survey across 49 states, only 7% of primary care physician practices reported scheduling preventive visits as a high priority.
Stroke, heart disease, cancer, and lung diseases — among the leading causes of death in the U.S. — have not gone away just because Covid-19 has emerged. Patients and doctors are potentially missing or ignoring worrisome symptoms unrelated to Covid-19 and not addressing them. Interrupting care for patients with chronic conditions can lead to disastrous outcomes.
While the nation understandably focuses its hospitals’ preparedness for the surge of Covid-19 patients, much of the pandemic response occurs in outpatient settings and increasingly through telemedicine. Efforts by doctors and nurses to triage patients to the safest settings to reduce risk of Covid-19 transmission is more important now than ever before. Many primary care practices have transitioned more than 60% of in-person visits to telemedicine, with 40% of doctors and staff mostly using telephones and 23% using video visits.

Mina’s story, however, reveals an overwhelming unpreparedness of our nation’s outpatient centers to care for high-risk patients during this pandemic. Doctors are struggling to decide if our patients’ chances of surviving are better if they stay home or go to the hospital.
Physicians have been given limited guidance for making the nuanced decisions required to treat patients who don’t have Covid-19 but who are both clinically complex and at high-risk for complications if they developed the infection. The absence of standardized guidelines for using telemedicine or the infrastructure to deliver care at home can lead to delayed diagnosis and treatment. Even though Mina had help to navigate the medical system, she experienced this delay. For others without such assistance, delays of care can be damaging — even deadly.
Patients’ fears compound these complex decisions. My colleagues and I weekly receive calls from patients with symptoms that would normally require an emergency department or office visit. Take Craig, a 67-year-old with a history of heart attacks, who called me to report that he was experiencing chest pain and was worried about another heart attack. Under normal circumstances, I would have told him to go to the closest emergency department. But he refused to go to a hospital under any circumstances after his friend was diagnosed with coronavirus. These fears are real, common, and affect patients and their doctors. While Craig is an engaged patient who proactively called me, giving me a chance to intervene, I know that there are many others who avoid communicating symptoms with their doctors out of fear.

Along with uncertainty about deciding whether to risk the possibility of exposing patients to the coronavirus, doctors’ fear of becoming infected themselves can change how they practice medicine. This anxiety is fueled by not knowing if their teams can prevent them from becoming ill. In early April, 58% of doctors and staff in primary care practices lacked personal protective equipment, and more than 30% of them expressed frustration with constantly changing or conflicting guidelines. With little access to protective gear, confusion about who needs it, and stories of health care workers getting sicker due to higher exposure, doctors are becoming more willing to implement telemedicine.
We urgently need strategies for the complex scenarios that doctors now face to balance care for non-Covid-19 conditions with the desire to protect their patients from being exposed to the virus that causes it. Developing new approaches to care for patients in the time of Covid-19 may reduce future waves of collateral damage with losses that could be as significant those from the virus itself.
Virtual care can help reach many patients, but most medical centers do not yet have the infrastructure in place to fully support highly efficient telemedicine. In addition to providing telemedicine-enabled devices, medical centers must have systems to identify and prioritize which patients will benefit from them the most. For example, they can distinguish their patients who are at high risk of becoming sick using predictive analytic models, may engage in using technology, and could be taught how to use telemedicine tools.
Even though some new clinical guidelines are being released during the pandemic, medical teams require more guidance on how to implement telemedicine. Doctors can benefit from help deciding which scenarios warrant a video, phone, or in-person visit. Remote visits also could be supplemented using home-based lab collection and home monitoring devices to provide information on blood pressure, blood oxygen levels, blood sugar, heart rhythms, and perform audible lung and heart exams.
Even with advanced remote monitoring, some patients will still need in-person evaluation. Emergency care is essential for patients who are critically ill, even with the risk of Covid-19 exposure. That is especially true for patients who face challenges accessing telemedicine. In a survey of primary care physicians, 72% said they have patients who are unable to access telehealth because they do not have access to a computer, smartphone, or the internet. These patients may need help learning how to use telemedicine devices or in-person evaluations such as those available through hospital-at-home and home-based primary care programs.
Fully connecting with patients who live with chronic conditions will require the U.S. to bolster its ambulatory infrastructure and financing. Primary care stimulus packages could help support the expansion of the hospital-at-home approach, along with home-based primary care and remote monitoring services. Similarly, an expansion of Medicaid would cover broad medical care for the newly uninsured and those with pre-existing conditions.
While it will take time to develop deliberate guidance, the nation needs urgent action to mitigate patients’ and doctors’ anxiety and hep remove the Covid-19 blinders to prepare for the collateral damage of non-Covid-19 medical conditions.
Reshma Gupta, M.D., is an internal medicine physician and medical director for value and population care with University of California Health in Sacramento, Calif. She thanks Dr. Reena Gupta for her input on this essay.

Collateral damage occurs when doctors and patients wear ‘Covid-19 blinders’

FDA tightens rules on COVID-19 tests aimed at corralling bad actors

The FDA now expects COVID-19 antibody testmakers to submit requests for emergency use authorization of their assays within 10 days of test validation, backing away from its “highly flexible” stance in mid-March not requiring the application if the manufacturer notified the agency that it was selling the test and affirmed that it was validated and labeled as unapproved.

The FDA temporarily lowered the bar in order to facilitate nationwide access to testing but some opportunists have taken advantage of the situation with substandard products, including an electronics salesman hawking an unauthorized home test kit and a former doctor convicted in a fraudulent gold-peddling scheme.

In a statement, the agency says, “Flexibility never meant we would allow fraud. We unfortunately see unscrupulous actors marketing fraudulent test kits and using the pandemic as an opportunity to take advantage of Americans’ anxiety.”

https://seekingalpha.com/news/3568338-fda-tightens-rules-on-covidminus-19-tests-aimed-corralling-bad-actors