DIY vax maker aims to beat pharma to Covid shot—to start by injecting himself

The biohacker who injected himself with CRISPR is back. This time, he’s setting out to solve a problem at the forefront of everyone’s mind—the need for a COVID-19 vaccine—and he thinks he can beat biopharma to it.

Nevermind that companies like Moderna and AstraZeneca are racing vaccine candidates into and through the clinic at a speed never seen before, and the U.S. government has set up a Manhattan Project-style initiative aptly dubbed “Operation Warp Speed,” which aims to deliver 100 million doses of a viable COVID-19 vaccine by the end of the year. That’s still too slow for Josiah Zayner.

“This is the perfect opportunity for biohackers,” Zayner told Bloomberg. “We can move science faster.”

His plan is based off a Science paper published in May showing that a DNA vaccine seemed to provoke an immune response against SARS-CoV-2, the virus that causes COVID-19. The researchers developed multiple vaccines expressing different forms of the virus’ spike protein and tested them in monkeys.

Along with collaborators in Mississippi and Ukraine, Zayner wants to reproduce that experiment in humans—themselves—and livestream the process over several weeks, Bloomberg reported.

“They said specifically what they used, which is really easy to recreate,” Zayner told Bloomberg, speaking from the West Oakland, California, headquarters and lab of his company, The Odin. “You know, it works in monkeys. Let’s test it on humans.”

The scheme, dubbed Project McAfee, after the antivirus software, is possible thanks to the availability of new tools and technologies—including viral DNA—to the general public. Zayner ordered the same spike protein the researchers used in their DNA vaccine from a DNA synthesis company, having it put in a solution that could be injected into his muscles, Bloomberg reported.

Zayner and his partners plan to inject themselves with the vaccine and then take antibody tests regularly to see if their bodies mount an immune response, Bloomberg reported.

Zayner and David Ishee, one of his partners and a self-taught scientist in Mississippi, think the project could pierce the veil on biotech research and scientific experiments.

“I want people to learn something from this,” he said, “So it’s no longer this big black box of what science, clinical trials and all this stuff is,” Zayner told Bloomberg.

“I would like to see a future where biotech is less arcane,” Ishee said. “But the most realistic thing that will come of this is that maybe people will understand the news they’re reading better.”

But Hank Greely, a bioethicist at Stanford University, said the approach has its limits.

“If he has and uses the appropriate biosafety precautions, I see nothing wrong with his efforts to replicate the macaque work in living human cells,” Greely told Bloomberg. “If he can do that, it might be a somewhat useful scientific finding.”

The keywords are “living human cells.” Compare that to the massive clinical trials underway, or soon to be, for vaccines from Moderna, AstraZeneca, Pfizer and BioNTech. Earlier this month, Moderna finalized the design for a 30,000-patient phase 3 study, while AstraZeneca and the University of Oxford have already started a phase 2/3 study involving more than 10,000 people.

“At best he’ll have three people who have received this DNA vaccine,” he said. “It’s hard for me to see his administration of a vaccine to three people as producing any useful scientific knowledge, except perhaps in the unhappy result that they have terrible reactions to it. But even then, it’s just anecdotal, a caution but not a proof.”

And that’s not all—Zayner may pull off his experiment, but copycats may not.

“Even if he does it well, people copying him poorly could be hurt. And for what?” Greely said. “Uncontrolled experiments with doubtful, non-standardized ingredients and conditions are not likely to lead to scientific knowledge that will produce vaccines faster.”

https://www.fiercebiotech.com/biotech/diy-vaccine-maker-aims-to-beat-pharma-to-a-covid-shot-and-he-ll-start-by-injecting-himself

Chiasma gets FDA OK for acromegaly pill years after near-catastrophic rejection

Nearly four years ago, the FDA left for dead Chiasma’s pill for abnormal limb and organ growth based on concerns over the design of a late-stage pivotal trial. But now that Chiasma has picked itself up off the floor and scored an FDA nod for its once-scorned drug, that nightmare scenario is a thing of the past.

Chiasma’s Mycapssa (octreotide) has become the first FDA-approved oral therapy to treat acromegaly, a rare disorder in which overproduction of human growth hormone leads to abnormal enlargement of patients’ extremities and internal organs, the drugmaker said.

Acromegaly, made famous by the late professional wrestler Andre the Giant, is believed to affect around 24,000 U.S. patients at any time.

The FDA approved Mycapssa as an oral version of somatostatin analogs, a group of injectable drugs that slow the overproduction of growth hormones that lead to serious complications in patients with acromegaly. There are around 8,000 U.S. patients each year treated with a somatostatin analog, Chiasma said, usually after undergoing an unsuccessful surgery to remove the pituitary gland tumor that causes growth hormone overproduction.

Chiasma CEO Raj Kannan applauded Mycapssa’s approval as a major step for the small but visible acromegaly community—and a big win for Chiasma’s commercial hopes.

“As we move into this next exciting phase as a commercial company, we are prepared to execute on a successful U.S. launch by working with healthcare providers to bring Mycapssa to as many patients who could benefit from it,” Kannan said.

Mycapssa’s long-gestating green light comes nearly four years after the FDA knocked down the drug’s application for approval based on design concerns around a pivotal phase 3 trial.

That setback caused Chiasma to lay off 33% of its workforce in August 2016 after building up a team of 65 full-time employees to handle the expected commercial launch of the drug. After working through the issues in the FDA’s complete response letter, Chiasma launched the successful phase 3 trial that eventually secured the FDA’s go ahead.

Mycapssa will help replace monthly injection regimens for patients currently treated with somatostatin analogs and has a similar safety profile to those drugs with the injection site reaction issues. The drug’s labeled side effects include gallstone risks, high and low blood sugar levels, abnormal thyroid and heart function, and decreased vitamin B12 levels.

Chiasma is aiming to launch Mycapssa in the fourth quarter pending a “planned manufacturing supplement to the approved NDA,” the drugmaker said in a release.

The company has built up a team of 45 sales professionals to help with the rollout and “plans to offer an array of patient support services ranging from assistance with insurance providers and specialty pharmacies to giving patients support to help incorporate Mycapssa seamlessly into their daily living,” Chiasma said.

https://www.fiercepharma.com/marketing/chiasma-secures-long-awaited-fda-nod-for-acromegaly-tablet-mycapssa-years-after-near

Pfenex announces positive European CHMP opinion for PF708

Pfenex (PFNX -4.4%) said Theramex, the European commercialization partner for Pfenex and Adalvo, receives a positive opinion for PF708 from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency.

PF708 will be branded in Europe as Livogiva (teriparatide injection), a biosimilar product to the reference medicine Forsteo indicated for postmenopausal women with osteoporosis.

Additionally, Adalvo enters into a commercialization agreement with a large pharmaceutical company to commercialize PF708, upon receipt of marketing authorization, in certain in Latin American countries.

https://seekingalpha.com/news/3586627-pfenex-announces-positive-european-chmp-opinion-for-pf708

Fauci hints at new approach to COVID-19 testing

June 26, 2020

Anthony Fauci, the nation’s top infectious disease doctor, said federal health officials are considering a new strategy for coronavirus testing as cases spike in states across the country.

Fauci told The Washington Post in an interview Thursday night that officials are having “intense discussions” about adopting a technique known as pooled sampling — grouping together multiple individuals’ COVID-19 tests to boost testing capacity.

Under this approach, if the virus is not detected in a combined test tube, all the patients can be deemed negative; if it comes back positive, each sample is tested individually.

“What you need to do is find the penetration of infected people in your society,” Fauci said. “And the only way you know that is by casting a broad net.”

A series of studies since April have pointed to the technique’s effectiveness in detecting COVID-19. A peer-reviewed simulation published Tuesday in JAMA Network Open found that pooled sampling could reduce the number of tests required by up to 84 percent, as long as it is deployed in locations with relatively low disease prevalence.

The technique of pooling samples of multiple patients — usually between five and 20 — was pioneered to combat a syphilis outbreak during World War II and has since been used in testing for HIV, hepatitis B and C, and other viruses.

Fauci’s remarks came the same day that the U.S. set a new daily record for coronavirus cases. His comments also followed an announcement that the White House coronavirus task force will hold a press briefing on Friday, its first in roughly two months.

Fauci, a member of the White House coronavirus task force, said at a congressional hearing that testing for COVID-19 is ramping up, despite comments from President Trump last weekend that he ordered testing to be slowed down. Trump said Thursday that he made the comment “jokingly,” after saying earlier in the week that he doesn’t joke about testing.

The U.S. conducted 637,587 tests Thursday, according to the COVID Tracking Project. City officials in Wuhan, China said they conducted 1.47 million tests in a single day last month using pooled sampling.

“Pooling would give us the capacity to go from a half a million tests a day to potentially 5 million individuals tested per day,” Deborah Birx, another member of the White House task force, told an American Society for Microbiology virtual conference this week.

Testing for COVID-19 requires two kits — fan extraction kit to take a sample from a patient, often through a nasal swab, and a kit used in a lab to detect the virus.

Early in the outbreak, the U.S. faced shortages of both types of kits. Pooled sampling addresses shortages in the second type of kit by allowing samples extracted from multiple patients to be tested together in the same test tube.

The technique has not been widely adopted in the U.S. due to regulatory hurdles and concerns over false negatives. Several peer-reviewed studies have identified the conditions in which pooled sampling can be safely deployed to detect COVID-19, saving significant time and testing material.

The Food and Drug Administration (FDA) has not officially authorized the technique, though it loosened guidance on June 16 to make it easier for labs to apply to use it.

Adm. Brett Giroir, assistant secretary for the Department of Health and Human Services, said on a call with reporters Wednesday that his agency is working to provide the FDA with additional data on the technique that could lead to a broader authorization for its use.

The JAMA Network Open paper published Tuesday found that pooled sampling was more efficient and cost-effective than individual testing as long as the disease prevalence stayed under 30 percent.

With a low disease prevalence of 1 percent, only 16 percent as many tests would be required as individual testing, according to the simulation.

Alhaji Cherif, a researcher at the Renal Research Institute in New York City who co-authored the paper, wrote in an email that these results show pooled sampling could be deployed in specific scenarios where the need for tests is high, but expected disease prevalence is low.

“The strategy can be very useful and cost-efficient in natural group settings, for example, in first responders, shift workers, classrooms, hospital departments, local clusters, households, conventions and events, long-term care facilities, to name but a few,” Cherif wrote.

Studies in Germany and Israel have also supported the technique’s efficacy at detecting COVID-19.

Before individual testing for COVID-19 became standard in the U.S. in late February, researchers at Stanford’s Clinical Virology Laboratory used pooled sampling to test nearly 3,000 patients in the Bay Area despite scarce testing kits.

The updated FDA guidelines issued earlier this month included a procedure for labs to internally validate that a testing kit already approved under the FDA’s Emergency Use Authorization is compatible with pooled testing.

“The steps taken today by the FDA further demonstrate how we are proactively working with diagnostic test developers to facilitate new approaches and get more tests to more Americans more quickly,” the FDA wrote in a statement issued with the updated guidelines.

Rep. Max Rose (D-N.Y.) wrote letters to Giroir, Veterans Affairs secretary Robert Wilkie, and New York governor Andrew Cuomo June 19 urging them to start using pooled sampling.

“Pooled sampling can be a game changer to get large numbers of people tested quickly –including for nursing homes, hospitals, businesses, and public housing among many others,” Rose wrote in the letters to Giroir and Cuomo. “For businesses of all sizes, this can help them reopen and stay open knowing they can test workers in large numbers and on a regular basis if needed.”

https://thehill.com/policy/healthcare/504671-fauci-hints-at-new-approach-to-covid-19-testing

Chiasma shares halted pending news on U.S. Mycapssa application

Nasdaq has suspended trading in Chiasma (CHMA -1.5%) pending the release of news, in this case related to the FDA decision on its refiled marketing application seeking approval of Mycapssa (octreotide) for acromegaly. The agency’s action date is today.

The company received a CRL in April 2016 in response to its first submission citing the need for an additional clinical trial. It dutifully conducted a new study, OPTIMAL, that met the primary endpoint, announcing the positive outcome in July 2019.

https://seekingalpha.com/news/3586589-chiasma-shares-halted-pending-news-on-u-s-mycapssa-application

Twitter’s Mixed Response to Dexamethasone Preprint

RECOVERY researchers posted a preprint of their dexamethasone trial results on the MedRxiv server this week. The findings suggest the steroid reduces mortality among the sickest COVID-19 patients. But some readers on Twitter remain skeptical, saying clinicians need more data — and the data need to be peer reviewed.

One of the trialists, Martin Landray, MBChB, PhD, Nuffield Department of Population Health, University of Oxford, UK, announced the data release on Twitter earlier this week.

“Pre-print now available. Huge credit to all those #NHS who have made this possible – most of all to the patients, their families and their loved ones. Thank you all,” the epidemiologist tweeted.

The study authors report that dexamethasone seems to reduce inflammation caused by the immune system. The drug reduced deaths of patients on ventilators by 29%, and deaths of patients on oxygen by 21.5%, they write in the preprint. The researchers compared data from 2104 severely ill coronavirus patients who received a daily, low dose of dexamethasone, orally or intravenously, with outcomes from 4321 patients who received standard care.

“Med Twitter” reacted swiftly.

Some of those posting on Twitter welcomed the news of a potentially safe, inexpensive drug to help in the fight against the novel coronavirus.

“Oh look. The RECOVERY preprint is out. I am glad I was a staunch advocate we adopt this asap as it was not a typical ‘medicine by PR’ because the manuscript is sound…Change your practice now,” tweeted oncologist Vinay Prasad, MD, from the University of California San Francisco.

Prasad’s tweet references a press release on the paper distributed last week and widely covered in the media that declared, “The survival benefit is clear and large in those patients who are sick enough to require oxygen treatment, so dexamethasone should now become standard of care in these patients.”

However, not everyone was quick to appreciate the authority of the preprint. As with the press release, many Twitter users continued to push back against the idea of changing practice before seeing the fully published study.

“… My initial concern, after a very brief skim of the article, is that the raw data and statistical methods (including relevant code/parameters) aren’t available for reproducibility purposes. Could the preprint please be updated with links to these resources?” the genomicist Steve Moss queried.

And others underscored the importance of knowing when to use the drug — and when not to use it.

“This is key: the steroid drug dexamethasone likely harmful if taken in early illness. But dexamethasone can prevent mortality in late #COVID19 illness when on oxygen or ventilator. Timing of the use is EVERYTHING!” tweeted Harvard epidemiologist and public health scientist Eric Feigl-Ding.

In addition, many Twitter users said it was important to proceed with caution to avoid a recurrence of recent missteps that resulted from rushing ahead of data or normal scientific process. For example, some pointed to recent high profile retractions in major scientific journals such as The Lancet and New England Journal of Medicine, as well as the Food and Drug Administration withdrawal of its emergency use authorization for hydroxychloroquine and chloroquine, drugs once touted by the federal government as viable COVID-19 treatment.

https://www.medscape.com/viewarticle/933012

Physician Shortage Projected to Worsen Through 2033

Demographic factors such as population growth and aging are the primary drivers of the expected physician shortfall.

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KEY TAKEAWAYS

By 2033, the shortfall of physicians is expected to range from 54,100 to 139,000, according to a new report commissioned by the Association of American Medical Colleges.

The projected shortage is expected to be greatest among primary care physicians, with the 2033 shortfall ranging from 21,400 to 55,200.

Retirements of physicians are expected to put downward pressure on the supply of physicians.

Physician demand will grow significantly higher than supply through 2033, according to a new report commissioned by the Association of American Medical Colleges (AAMC).

The projected shortage of physicians is worsening. Last year, the AAMC projected the shortfall of physicians at as many as 122,000 by 2032. The new report released today projects the shortfall at as many as 139,000 physicians by 2033.

The new report includes several key findings:

• By 2033, the projected shortfall of physicians ranges from 54,100 to 139,000.
• By 2033, the projected shortfall of primary care physicians ranges from 21,400 to 55,200.
• By 2033, the projected shortfall of non-primary care physicians ranges from 33,700 to 86,700. The physician shortage in surgical specialties ranges from 17,100 to 28,700. The physician shortage in medical specialties ranges from 9,300 to 17,800. The physician shortage in other specialties ranges from 17,100 to 41,900.

Driving the data

Two demographic factors—population growth and aging—are the primary drivers of the projected increasing demand for physicians through 2033, according to the new report.

• Through 2033, the U.S. population is expected to grow by 10.4%, rising from about 327 million people in 2018 to 361 million people.
• The population under age 18 is projected to grow 3.9%, which would lead to low growth in demand for pediatric specialties.
• The population of people 65 and older is projected to grow by 45.1%, which would lead to high demand for physician specialties that care for geriatric patients.
• Retirements are expected to thin the ranks of physicians through 2033. “More than two of five currently active physicians will be 65 or older within the next decade. Shifts in retirement patterns over that time could have large implications for physician supply. Growing concerns about physician burnout, documented in the literature, suggest physicians will be more likely to accelerate than delay retirement,” the new report says.

Coronavirus pandemic impact

The coronavirus disease 2019 pandemic is expected to have several short- and long-term impacts on the physician workforce, the new report says.

• The pandemic is likely to affect the physician educational pipeline such as cancelation of clinical rotations and other interruptions in physician education.
• The pandemic is likely to affect physician regulations such as changes in licensure.
• The pandemic has already affected the practice of medicine such as the explosive growth of telemedicine.
• The pandemic will have an uncertain effect on physician workforce exits, with early burnout-induced retirements potentially lowering the physician supply and the weakened economy potentially increasing the physician supply as doctors delay retirement.
• The pandemic will likely affect the specialties that new physicians select such as an increased number of doctors choosing to work in infectious disease.

https://www.healthleadersmedia.com/clinical-care/physician-shortage-projected-worsen-through-2033