Tiziana takes a deep breath and targets Covid-19

The addition last week of Roche’s anti-IL-6 receptor antibody Actemra to Chinese guidelines for treating patients with Covid-19 has prompted Tiziana Life Sciences to speed the development of its similarly-acting TZLS-501 for the same use. The group’s stock is up 173% on London’s AIM so far today.
This could be somewhat overenthusiastic: for one thing, TZLS-501 is still preclinical. For another, two of the three approved anti-IL-6R MAbs carry black box warnings of the risk of serious infections in patients with pulmonary disease – and the third may not be given to patients who already have lung infections. Planning to give these drugs to Covid-19 patients is a bold move.
Actemra, long approved for rheumatoid arthritis, has reportedly been used in 20 patients with severe Covid-19 infections in China, lowering body temperatures in all of them within one day. All but one were discharged from hospital within a fortnight.
This approach seems to have been prompted by suggestions that Covid-19 patients might respond to the infection by overproducing inflammatory cytokines such as IL-6 in the phenomenon called cytokine storm. In 2017 Actemra was approved by the FDA to treat cytokine release syndrome caused by Car-T treatment.
A further rationale has been provided by research published on March 3 indicating that viral load is associated with elevated IL-6 levels in severely ill Covid-19 patients. The researchers wrote that IL-6 “should be considered as a therapeutic target in critically ill patients with excessive inflammatory response”.

Approved anti-IL-6Rs
Product	Company	2020e sales ($m)	2024e sales ($m)	Notes
Actemra/ Actemra SC	Roche/Chugai	2,408	2,341	BBW of serious infections, including tuberculosis
Kevzara	Sanofi/Regeneron/ Asahi Kasei	355	570	BBW of serious infections, including tuberculosis
Sylvant	Eusa Pharma	–	–	Not to be given to patients with severe infections
Source: EvaluatePharma, drug labels. BBW=black box warning.

According to the WSJ, Regeneron and Sanofi are also repurposing their anti-IL-6R, Kevzara, for the new virus. The partners intend to start a clinical trial of their MAb – which is widely approved for rheumatoid arthritis but not for cytokine release syndrome – in severe Covid-19 as soon as possible. The third approved IL-6R, Eusa Pharma’s Sylvant, does not appear to be under investigation for the coronavirus.
In a tizzy
The advantage of these approved products, as opposed to novel drugs in development such as Gilead’s remdesivir, is that they can be used off-label relatively easily, and their production and distribution ramped up relatively quickly. But there is no getting away from their poor safety profile.
This has not stopped Tiziana, of course. The safety profile of TZLS-501, like its efficacy in Covid-19 or anything else, is unknown, because it is yet to be given to humans. Neither does it have any of the advantages of the approved products.
There is as yet no evidence that any of the dozen or so other IL-6Rs in clinical or preclinical development are being aimed at Covid-19. Perhaps when some of these groups see how nicely Tiziana has done on the markets today they might make their own announcements.
Still, giving an untried drug to severely ill patients, many of whom will be elderly or have comorbidities or both, is taking a big risk. And that would be true even if the molecule did not belong to a class known to be potentially dangerous to patients with lung infections.

The anti-IL-6R pipeline
	Project	Company
Filed
	Satralizumab	Roche/Chugai
Phase III
	Olokizumab	UCB
	Clazakizumab	Lundbeck
	BCD-089	Biocad
	BAT1806	Bio-Thera Solutions
Phase I
	EBI-031	Roche/Sesen Bio
	MEDI5117	Astrazeneca
	MSB11456	Fresenius
	LusiNEX	Mycenax Biotech
	FB704A	Fountain Biopharma
Preclinical
	Inflammation FynomAbs *	Johnson & Johnson/Mitsubishi Tanabe
	TZLS-501	Tiziana Life Sciences/Light Chain Bioscience
* Also inhibits IL-7a. Source: EvaluatePharma.

https://www.evaluate.com/vantage/articles/news/tiziana-takes-deep-breath-and-targets-covid-19

Few groups have developed Covid-19 diagnostics – but this will change

The Covid-19 outbreak means medics are now turning to Western diagnostics companies for genetic tests for the virus. Five of the top 10 IVD developers have responded to the call, alongside smaller groups and independent medical centres in Europe and the US.
Roche led the charge, claiming to have put the first Covid-19 test on a commercial footing at its fourth-quarter results conference on January 30 (Coronavirus stock hype proves infectious, February 27, 2020). Danaher and Thermo Fisher have also both made tests available, and France’s Biomérieux has two on the way.
So far no Covid-19 test has obtained FDA approval or clearance. Those that are on sale in the US have been made available under Clia waivers, whereby the facility where the tests are conducted is regulated, rather than the tests themselves.
Three tests, however, have obtained European CE mark. Most recent, announced this morning, is the Viasure Sars-CoV-2 real time PCR detection kit, developed under a partnership between Becton Dickinson and the much smaller group Certest Biotec. The micro caps Novacyt and Co-Diagnostics also have CE-marked tests.
Forthcoming
Genetic tests themselves are reasonably easy to create and deliver. The virus’s genome was sequenced and published early on in the outbreak, and because of coronaviruses’ propensity to mutate it has been repeatedly sequenced since.
Devising a genetic test for the virus is a case of picking parts of this genome to identify in a sequence of viral RNA taken from a patient. Thermo Fisher’s test, for example, checks for three target sequences that are unique to the Covid-19 virus – the ORF1ab gene and regions that code for the S and N proteins.
Consequently the companies named here represent a tiny fraction of the number actually working on Covid-19 diagnostics. The FDA initially said that tests to be used in the US would have to obtain an emergency use authorisation, the means by which the agency permits use of a non-approved drug or device to respond to a declared emergency. It issued one such authorisation to a test developed by the CDC on February 4.
A few weeks later the FDA relaxed its rules. Under pressure to accelerate the availability of Covid-19 tests, it said on February 29 that Clia-certified labs could begin using their tests without needing an EUA, though they would still have to submit an application for one 15 business days after validating their new test. The same day, the FDA awarded an EUA to a test developed by a New York-based public health facility.
In a briefing on March 7, the FDA Commissioner Stephen Hahn said that the agency had received more than 100 requests for an EUA template, adding that 36 companies had sought the FDA’s assistance with development and validation of tests they plan to bring through the EUA process. Most of these companies will already be selling their tests in the US, but it is only when the EUAs are granted that it will become clear who they are.

Top 10 in vitro diagnostics companies’ work on Covid-19
	Annual sales ($bn)
Company	2019	2024	CAGR	Covid-19 diagnostic?
Roche	11.1	14.2	+5%	Yes, test launched
Abbott Laboratories	7.7	10.1	+6%	No, but has donated testing instruments to China
Danaher	6.6	8.2	+5%	Yes, test launched
Siemens Healthineers	4.6	5.6	+4%	No, though has tests for other coronaviruses
Thermo Fisher Scientific	3.4	4.0*	+3%	Yes, test launched
Becton Dickinson	3.1	3.9	+5%	Yes, test CE marked
Sysmex	2.7	3.7	+6%	No, mainly cancer-focused
Exact Sciences	0.9	3.5	+32%	No, cancer-focused
Biomérieux	2.4	3.3	+6%	Yes, two tests in development, launch of first imminent
Ortho-Clinical Diagnostics	1.9	2.1	+2%	No, though has tests for other viruses including HIV
Rest of market	15.0	22.2	+8%
Total market	59.4	81.0	+6%
*Does not include forecasts for Qiagen, which Thermo Fisher is to acquire. Source: EvaluateMedTech.

https://www.evaluate.com/vantage/articles/news/policy-and-regulation/few-groups-have-developed-covid-19-diagnostics-will

Gym one of the germiest places around

Free weights have 362 times more bacteria than a toilet seat, according to a study performed by EmLab P&K, a finding that could bring sweat to your brow before you even launch into your first bicep curl—especially with the new coronavirus in mind.

In the wake of COVID-19, fitness centers are sending emails to members about prevention measures. Most include encouragement to stay home if you’re feeling sick. There’s also plenty of phrasing about amping up established disinfecting efforts.
“We’ve been instructing staff to wipe down basically anything that humans will touch—seats you sit on while waiting for class, extra wiping down of door knobs, mic sets for the instructors, etcetera,” says Mariah Ostia, Flywheel Center City’s studio manager.
Members are being asked to do their part, too.
“Avoid kissing, hugging, and the sharing of cups and water bottles,” reads a Barry’s Bootcamp email.
Add high-fiving to that list, says John Zurlo, Jefferson Health’s division director of infectious disease. (His recommendation: celebratory elbow bumps instead.)
Wondering what else you can be doing to dodge germs at the gym? Zurlo shares some advice to practice on your next visit. Topping the list: keep your hands away from your face.
“If you touch a surface where someone has sneezed, like a gym bench, and then rub your eye with your pinky finger, the virus could spread,” says Zurlo. “Our nose, mouth, and eyes have mucus membranes, and this is where respiratory infections like the coronavirus and the flu enter into the body.”
Cue towels. Carry two with you—one to spread across each machine and one to wipe sweat from your face. Just remember to remain conscious of what surfaces the fabric touches, and which sections are still clean. If needed, toss your towel mid-workout in exchange for a new one.
Tissues work as barriers, too, and are especially useful in situations where a towel might feel clunky. Need to adjust sweaty glasses or scratch an itchy nose? Those are prime jobs for a Kleenex.
Likewise, grab a tissue or paper towel to avoid hand contact with water fountain handles. And when you go in for a drink, do so with care.
“It seems like common sense, but try not to touch your cheek to any part of the metal on the water fountain,” says Zurlo. “You could also let the water run for a few seconds.”
Since running to the bathroom sink in between every gym machine isn’t realistic, Zurlo suggests using water breaks as reminders to get those hands clean.
“Probably more so than the soap, rinsing for the full 20 seconds is crucial,” says Zurlo of hand-washing.
Twenty seconds: it’s roughly the amount of time it takes to sing Happy Birthday twice. Or, as noted in a list by the Los Angeles Times, the chorus of Lizzo’s Truth Hurts, Toto’s Africa, or Prince’s Raspberry Beret—all prime additions for your gym playlist.
Hand sanitizer is also handy, and with the coronavirus of concern, Zurlo says you needn’t be too concerned about how often you’re using it.
“In medicine, every time we walk into a patient room, we use hand sanitizer, and when we walk out of the room we use it again—so for physicians, sometimes that means 40, 50, 60 times a day,” says Zurlo. “In my personal life, I’m not using it all the time, but I don’t know if I’d set any limit at the gym.”
Use enough to cover every part of your hands, including rings. And as with the hand sanitizer, utilize sanitizing wipes regularly, too.
“It’s good gym etiquette to wipe down machines after you use them,” notes Zurlo. “It’s a big step to also be wiping down every machine before use, but at this point I can’t see a downside to it.”
Ultimately, how to navigate the gym comes down to awareness. To prevent injury, you have to pay attention to form. To prevent sickness, you have to pay attention to what you touch.
Being aware of those around you is important, too, says Zurlo. If someone’s coughing, move.
But as long as you remain mindful, Zurlo says, there’s no need to fear going to the gym, at least for now.
“Maybe I’d feel differently if we start to get hundreds or thousands of (coronavirus) cases in Philadelphia, but I’m certainly not avoiding my local fitness center,” says Zurlo, who, at the time of the interview, was heading there soon. “I’m just being more cognizant of people around me and of my hands—washing them and 100% keeping them away from my face.”
https://medicalxpress.com/news/2020-03-gym-germiest.html

Italy shutting all stores except pharmacies and food shops

Prime Minister Giuseppe Conte said Wednesday that Italy would shut all stores except for pharmacies and food shops to curb the spread of the novel coronavirus pandemic.
“We close shops, bars, pubs and restaurants. Home delivery is allowed,” Conte said in a national television address as the virus has killed 827 people and infected more than 12,000 in Italy.
https://medicalxpress.com/news/2020-03-italy-pharmacies-food.html

US considering ban on travelers from Europe over virus

The United States is weighing a ban on travelers from Europe to slow the spread of the coronavirus, a senior US official said Wednesday.
“The question is a live question about how to treat Europe as a whole,” said Ken Cuccinelli, the acting deputy secretary of the Department of Homeland Security.
“That is not to the level of using legal authorities to block travel yet. But it is under consideration,” he told a congressional hearing.
“As each country, or in this case region, becomes more and more problematic it obviously gets reviewed on a day-to-day basis,” Cuccinelli told the House Homeland Security Committee.
“Europe presents a unique problem,” he said, pointing to the Schengen Area that maintains open borders between most of the Western European countries.
Cuccinelli, who is also acting director of US Citizenship and Immigration Services, said that Italy, the European country worst hit by the COVID-19 virus, is pre-screening passengers on all direct flights to the United States.
But Cuccinelli said the United States does not have adequate resources to screen travel by Italians or others who are flying indirectly to the United States from Europe.
He gave no additional information on the possibility of a ban.
Earlier a top government health expert said the largest threat to the country with respect to the virus is transmission from Europe.
“Where our real threat is right now is Europe,” said Robert Redfield, director of the Centers for Disease Control and Prevention.
“That’s where the cases are coming in from. If you want to be blunt, Europe is the new China,” he said.
https://medicalxpress.com/news/2020-03-europe-virus.html

6 ways new rules for opening health record access will impact industry

New federal rules around data-sharing aim to give patients unprecedented access to their healthcare information much the way they already manage their finances or travel information.
A rule from the Office of the National Coordinator for Health IT (ONC) will require patients are able to access their health information and share it with third-party apps.
“A core part of the rule is patients’ control of their electronic health information which will drive a growing patient-facing healthcare IT economy, and allow apps to provide patient-specific price and product transparency,” said Donald Rucker, M.D., National Coordinator for Health Information Technology, during a call with reporters.

Under the rule, hospitals and doctors are required to provide software access points, or endpoints, to their EHR databases so that patients can download these records to their smartphones. The rule also aims to penalize information blocking, or anti-competitive behavior that hinders the exchange of medical information.
Those are just a few major changes included in 1,244-page rule released Monday that will have huge implications for providers, health IT vendors and health information exchanges.
While there likely won’t be an immediate impact in the industry, the regulations could shake up the healthcare market in the long-term, stakeholders say. “These rules plant patients at the center of healthcare delivery to give them control of their data and enable them to direct it to whoever they want. That’s a reality now under these rules,” said Jeff Coughlin, senior director of federal and state affairs at the Health Information Management and Systems Society (HIMSS).
Here’s a look at major changes industry stakeholders can expect.

1. Health data will be easier to access

Patients will now be able to securely and easily obtain and use their electronic health information from their provider’s medical record for free, using the smartphone app of their choice, according to ONC.
As a condition of health IT certification, electronic health record (EHR) vendors will have to enable the export of electronic health information (EHI) for a single patient’s data.
This means that a patient would be able to download all the health information that a hospital has in their medical record, not just what is in the patient portal, according to Jeff Smith, vice president of public policy at the American Medical Informatics Association (AMIA).

Under the rule, EHR vendors also will have to enable an export all of the patient records when a health care provider is switching health IT systems.
“Right now, when a provider switches EHR vendors, the vendor is only required to provide the summary of care records. This new requirement will potentially create the ability for providers to switch EHR vendors more easily and more completely,” Smith said.
EHR companies have 36 months to comply with that requirement.

2. Information blocking will be prohibited

The rule seeks to prevent information blocking practices by healthcare providers, vendors, health information exchanges, and health information networks. That provision goes into effect in six months.
ONC established eight “exceptions” to the information blocking ban to allow clinicians and hospitals “common-sense operational flexibility,” including protecting patient privacy and security as well as handling situations where moving data is technically infeasible.
Providers will not violate the information blocking rule if they try to educate patients about the privacy and security risks posed by the apps they want to use, ONC leaders said.

3. The information blocking ban lacks teeth, for now

The ONC rule doesn’t include enforcement in the form of civil monetary penalties for information blockers.
Steven Posnack, Deputy National Coordinator for Health IT, said ONC was working with the HHS Office of the Inspector General on new regulations to establish civil monetary penalties. That rule will be coming out soon, he said.
“I hope we do some strong enforcement on this. That will send a strong message to the industry, and I think the industry will be looking for that,” said Matt Michela, CEO of Life Image, a network for managing medical information.
“It will be easy for large organizations to drag their feet and slow this up,” he said.

4. No more “gag clause” on EHR screenshots

As a big win for researchers and doctors, health IT vendors are now prohibited from restricting the sharing of screenshots and videos of their screens.
Researchers and doctors have long advocated for sharing screenshots of EHRs as crucial to improving usability and safety problems.

Currently, many EHR contracts contain non-disclosure provisions that either prevent or are perceived to prevent users from sharing information related to the EHRs, such as screenshots or video, and having an open discussion about problems, according to ONC.
Many EHR executives, including Epic CEO Judy Faulkner, had protested that provision in the proposed rule, saying it threatens companies’ intellectual property.
The new rule allows sharing screenshots but limits the screenshots or videos to only the information that’s necessary to communicate a health IT-related need.

5. Potential EHR market disruptions

Digital health, telehealth and Internet of Things (IoT) companies stand to benefit the most, as do insurance companies, according to Cowen investment analysts in a research note.
Digital health companies will get better access to data, which has been a barrier, and payors will see improvements in care management, the analysts wrote.
The new rules will result in near-term headwinds for EHR vendors and hospitals. The time frame to comply will require additional spending on the EHR vendor’s part. Health systems also face upfront implementation costs, Cowen analysts said.
In all, despite some near-term headwinds for certain players, Cowen analysts believe interoperability “can unlock much more value for the entire healthcare system.”
Many stakeholders believe the rules will significantly disrupt the EHR market.
Michela predicts that large healthcare companies that have been “slow-walking” interoperability are at risk to not survive.
“There will be new market entrants, once these APIs are created and it will create fundamentally new models that threaten very large established companies in the space. It will be interesting to see, in the next three to five years, how many companies will be disrupted that didn’t embrace interoperability, or minimally embraced it,” he said.

6. The move to an app economy will drive a bigger focus on privacy

Many stakeholders believe the rules will be a boon for Silicon Valley technology companies, who are already making inroads in healthcare, as well as digital health companies. This will help to spur more innovation in healthcare, stakeholders say.
But third-party apps will not be required to follow data blocking policies under ONC’s rule and are not covered under HIPAA. This raises serious privacy concerns about patients’ medical data and the potential misuse of data.
Former health IT policy leader Lori Evans Bernstein anticipates new privacy laws will take shape to fill in the gaps.
“Ultimately there will be a real update to HIPAA, and that will require Congressional action,” said Bernstein, who is the co-founder and chief operating officer of HealthReveal.
https://www.fiercehealthcare.com/tech/trump-administration-released-landmark-data-sharing-regulations-here-s-what-will-change

CMS to allow MA, Part D plans to waive coronavirus cost-sharing

The Trump administration has issued guidance to allow Medicare Advantage and Part D plans to waive the cost-sharing associated with coronavirus testing.
The Centers for Medicare & Medicaid Services released a moratorium (PDF) late Tuesday highlighting plan sponsors’ options to ease cost barriers associated with the spread of COVID-19. MA and Part D plans can waive members’ cost-sharing for tests or to visits to doctor’s offices, emergency departments or via telehealth.
Medicare Advantage and Part D plans also have the option to nix prior authorization requirements, waive limits on prescription refills, ease restrictions to home prescription delivery or grow access to telehealth, CMS said.

“The president directed CMS to make sure Medicare Advantage beneficiaries have access to healthcare services they need during this time,” CMS Administrator Seema Verma said in a statement.

“Medicare beneficiaries are at the greatest risk of serious illness due to COVID-19 and CMS will continue to do everything in our power to protect them,” Verma said.
The waivers, CMS said, will allow MA and Part D plans to work more effectively with providers and respond more nimbly to potential cases of the novel coronavirus.
President Donald Trump urged CMS to allow MA and Part D plans greater flexibility to respond to the growing outbreak, which has sickened more than 1,000 people and lead to at least 31 deaths in the U.S. to date, following a meeting with big-name health insurers on Tuesday.
That meeting included Trump, Vice President Mike Pence and members of the White House’s coronavirus task force.
“Working together with government leaders and industry partners, we can overcome this challenge and keep the American people safe and healthy,” America’s Health Insurance Plans CEO Matt Eyles said in a statement.
https://www.fiercehealthcare.com/payer/cms-issues-guidance-to-allow-ma-part-d-plans-to-waive-coronavirus-cost-sharing