Zoom forum changes the way ICU doctors treat desperately ill Covid patients

It was late April, near the height of the Covid-19 pandemic in the big cities in the northeastern U.S., and anesthesiologist Joseph Savino was puzzled. In two months, an unexpectedly high number of coronavirus patients had died in his intensive care unit at the Hospital of the University of Pennsylvania after a stroke caused by bleeding in the brain.

All were among 15 Covid-19 patients at the Philadelphia hospital who had been on a life-support technology called ECMO that is a last resort for patients when mechanical ventilators fail to help their virus-ravaged lungs.

ECMO, for extracorporeal membrane oxygenation — essentially an artificial lung — is high-risk, but still, the number of fatal brain bleeds seemed unusual, said Savino, a critical-care specialist. It was too low, however, “to draw any substantive conclusions” about cutting back the blood-thinning drugs they were giving other Covid-19 patients on ECMO, because blood clots, not bleeds, were seen as the major risk to survival.

So Savino described the dilemma on a virtual forum on Zoom, where dozens of critical-care experts from around the world meet each week to share their experiences with Covid-19 patients. A participant from Massachusetts General Hospital in Boston said two Covid-19 ECMO patients there had also died after suffering bleeding in the brain.

“We thought that couldn’t be a coincidence,” Savino recalled in an interview. He and his team immediately reduced the doses of blood thinners for their ECMO patients. Since then, the fatal bleeding strokes have stopped.

“If our Zoom conference was yesterday, change in practice is occurring today,” Savino said. He believes the forum is improving care for Covid-19 patients.

Swamped by overflowing ICUs and the myriad not-seen-before ways the novel coronavirus attacks the body, doctors caring for the pandemic’s sickest patients are scrambling to share their experiences with each other in real time, hoping to find ways to stanch Covid-19’s devastating toll. Some 200 physicians from several countries and dozens of states have participated in the Friday Zoom sessions. As cases have surged in new hot spots in the U.S., the calls are providing doctors from Florida to Texas to Arizona fresh from-the-trenches advice on how to use ECMO, a technology that can be lifesaving for some of the most severely ill Covid-19 patients but that has worrisome drawbacks.

The sessions have featured a range of issues, from technical matters such as the size of tubing used to connect patients to the ECMO machine, to what to do about patients whose lungs haven’t improved after weeks. Doctors have presented case studies highlighting the treatment and course of individual patients, and discussed the ethical challenges of determining which patients should be offered the technology.

The Zoom forum has also provided a window on the pandemic’s spread. The initial sessions in March and early April featured talks by European experts, including the head of the ICU at Paris’s huge La Pitié Salpêtrière Hospital, which treated some 80 patients with ECMO amid the pandemic’s surge in Europe. In April and May, as the epicenter shifted to the U.S., the 60- to 90-minute sessions often began with doctors from cities such as Boston, Seattle, and Philadelphia reporting on the number of patients on ventilators or ECMO in their ICUs.

This past Friday, a Houston doctor presented summaries of 11 patients on ECMO, many of them Hispanic. He mentioned a community hospital in Corpus Christi, near the hard-hit Rio Grande Valley, where about 150 patients were currently on ventilators, nearly as many as were on the devices at Mass. General at its peak. Scott Silvestry, a thoracic surgeon at AdventHealth Orlando, told the forum, “We are completely full with regards to our capacity to take Covid patients.”

“Science will ultimately have more answers. But there are a lot of people in hospital beds that need answers now.”

Joseph Savino, anesthesiologist at the Hospital of the University of Pennsylvania

At the invitation of Savino and Eduardo Rame, a cardiologist at Thomas Jefferson University Hospitals in Philadelphia and the chief organizer and moderator for the sessions, a reporter for STAT has been allowed to sit in on the virtual sessions since early May.

Rame initiated the forum in mid-March after learning from European specialists how the influx of Covid-19 patients was overwhelming ICUs in Paris and Italy.

“They were all scared,” he recalled. “They said, ‘It’s coming to you.’” He had recently left Penn to become enterprise chief of advanced cardiac and pulmonary vascular disease at Jefferson and knew from his Parisian conversations that preparing his team for the anticipated onslaught required making connections with other centers and knowing the capacity of ICUs and ECMO machines in his city and state.

He reached out to Savino and other former colleagues at Penn, and as the surge of patients began filling the ICUs in the Northeast corridor and other U.S. locations, the resulting collaboration quickly morphed into the weekly Zoom sessions. “By week four, we had 100 participants,” Rame said.

Sharing reports on individual cases doesn’t meet the rigor of clinical trials doctors typically rely on to order treatment for patients. “It isn’t science — yet,” Savino acknowledged.

But with patients showing up in the emergency room with a modest cough one day and crashing so fast they need to be put on a ventilator the next, the conventional methods of validating and disseminating clinical information through scientific journals and medical meetings weren’t sufficient. Even medical journal efforts to accelerate online publication of Covid-19 research as well as the rush by researchers to post results on so-called preprint servers before they are peer-reviewed have failed to satisfy critical-care doctors’ urgent need for help in the fast-moving pandemic.

“Science will ultimately have more answers,” Savino said. “But there are a lot of people in hospital beds that need answers now. The best we can offer is experiential learning, or learning from each other.”

 Specialists in critical care, ECMO, and advanced lung and heart disease comprise a small community in medicine. Many of the Zoom participants have logged at least a decade or two in critical-care medicine and had either trained or were trained by others on the sessions.

“In a trusted circle, where people have known each other for years, it carries a lot of weight,” said Silvestry, a regular on the forum.

An early question for the U.S. doctors was whether to offer ECMO at all. Some early reports raised doubts it would help Covid-19 patients.

One from Wuhan, China, where the pandemic originated, and published online in The Lancet Respiratory Medicine in late February, reported that five of six patients put on ECMO died. Small numbers, but a mortality rate over 80% was way too high for a high-cost technology that requires intensive nurse staffing to manage. Another study linked ECMO with poor results among patients with multiorgan failure — a problem in part because most of the pandemic’s sickest patients had other serious medical conditions.

Using ECMO to assist the lungs in patients with respiratory failure typically involves inserting a cannula or tube in a femoral vein in the groin from which blood flows through an oxygenator to add oxygen and remove carbon dioxide. The freshened blood returns to the body via a tube inserted into the right jugular vein for travel to the heart.

The blood’s almost continuous contact with the parts of the ECMO circuit promotes blood clots, while the skin punctures needed to insert the tubes raise the chance of bleeding. Emerging evidence that the virus attacks the blood vessels and other organs compounds some risks associated with the technology.

“This disease is challenging the very technical foundation of ECMO,” Rame said.

But all was not lost for ECMO. In April, the ASAIO Journal (for American Society for Artificial Internal Organs) published a case report of a 44-year-old emergency room doctor believed to be the first successful Covid-19 ECMO patient in the U.S. Rame invited Matthew Hartman, a cardiologist at Swedish Medical Center in Seattle and lead author of the report, to present the case on the forum.

The patient likely was infected while treating other Covid-19 patients in Seattle, where the first outbreak in the U.S. occurred. But he tested negative for the virus when he first arrived at an ER with shortness of breath and a fever. He was diagnosed with pneumonia and sent home. He returned the following day with worsening symptoms, tested positive for the virus and quickly went downhill.

“He went from a guy who was talking and needed some oxygen to being on a ventilator within like 24 hours,” Hartman recalled in an interview. His condition continued to deteriorate as levels of an inflammatory cytokine called IL-6 soared, indicating his immune system’s hyper response to the virus, and he developed an acute kidney injury. Laboratory markers indicated his risk of death was 80%.

“It was sort of ECMO or nothing,” Hartman said. “The consensus was while we don’t know if we can get him through it, he’s getting sick so quickly we should at least try.”

By the third day on ECMO, his inflammatory markers began to decline and his lung function improved. On the seventh day, he was “weaned” from the technology. Four days later, he was taken off the ventilator. He was discharged on his 24th day in the hospital and has recovered.

“It was sort of ECMO or nothing. The consensus was while we don’t know if we can get him through it, he’s getting sick so quickly we should at least try.”

Matthew Hartman, cardiologist at Swedish Medical Center

Hartman told the Zoom forum he and his colleagues don’t know what worked — whether it was ECMO or the various drugs the patient received. His treatment while on ECMO included the antiviral hydroxychloroquine (the drug later touted by President Trump but shown in studies to be ineffective against the virus); tocilizumab, a rheumatoid arthritis drug that blocks IL-6 (but that drug maker Roche recently reported failed to benefit Covid-19 patients in a randomized clinical trial); and high-dose vitamin C, a possible anti-inflammatory.

In the pandemic, as “people are getting sick and dying, a lot of therapies are being tried and not in a controlled fashion,” Hartman pointed out.

“It’s hard to say for the first case you did well, was it anything we did or did the stars line up,” Hartman said. And it was just one case. But it did suggest that ECMO, which itself isn’t a therapy, did its job by providing time for the patient to heal or benefit from his care. Given the patient’s kidney injury, the case also indicated people with multiorgan failure could be helped by the technology.

The Seattle case as well as other success stories from Paris and Japan offered encouragement to the Zoom sessions that ECMO was a viable option in the tool box for desperately ill Covid-19 patients, though it is still being used sparingly.

A Covid-19 registry being compiled by Mayo Clinic and the Society of Critical Care Medicine from 235 centers in 18 countries (including 202 centers from 38 states in the U.S.) indicates that about 30% of Covid-19 patients who are hospitalized end up being treated on mechanical ventilators and that just 2% are put on ECMO.

One value of the discussions, said AdventHealth’s Silverstry, is “knowing what we’re doing in Florida is the same as what they’re doing at Mass. General and Penn. We’re doing it the same way because of connections like this.”

Participants in the Zoom sessions have shared their experiences with a range of treatment strategies: Using wider diameter tubes to move blood from the body to the oxygenator and back to the body allows for increased flow, potentially improving oxygen levels and reducing risk of clots. Aggressive use of bronchoscopy to remove thick, sticky mucous may improve function of Covid-19-ravaged lungs. Pronating patients on ventilators and ECMO — flipping them regularly to lie on their stomachs and reduce pressure on the lungs — appeared to improve breathing function and oxygen levels, though it takes at least six people to flip a patient on ECMO and some doctors on the sessions said they believe pronating is more helpful before ECMO.

The insight Savino gained from his concern about fatal bleeding in the brain was part of a broader discussion that revealed wide variation in anti-coagulation regimens among centers offering ECMO.

Whether his team’s decision to reduce the dose of blood thinners prevented further brain bleeds is hard to know, he said. His ICU has had only a few new ECMO patients since then — too few to reach any conclusions. But he believes the discussions will lead to more rigorous research to identify the optimal strategy, thus advancing the science of ECMO.

The forum has also addressed another vexing problem: what to do about patients who stay alive for weeks on ECMO even though their lungs don’t seem to get better. In June, Rame invited doctors representing teams from Vienna and Chicago who had each performed an apparently successful lung transplant on a young woman whose lungs appeared beyond recovery.

Participants in the Zoom sessions congratulated the doctors on their accomplishments. Then they asked tough questions. A big worry, said Emily Blumberg, director of transplant infectious diseases at Penn, is that some patients continue to test positive for the coronavirus for weeks after the initial infection. Though doctors suspect the virus is inactive in such cases, “you would like the infection to be clinically or virologically resolved,” Blumberg said. “How you define resolution is very complicated.”

Other doctors noted that ECMO patients are often put in a drug-induced coma and paralysis to enable smooth operation of the technology. That can lead to weeks in an ICU bed that leaves them too deconditioned to be transplant candidates and makes it difficult to assess their neurological status and ability to give informed consent.

Moreover, “some patients just have long recovery phases,” Blumberg told the forum. “It’s important not to confuse a long recovery from ongoing pathogenesis that had led to irreversible destruction of the lungs.”

Indeed some doctors said they’ve seen patients with heavily damaged lungs recover after spending two months or longer on ECMO and it would be a waste of a scarce resource — donated lungs — and possibly shorten a patient’s life span to perform a transplant if the lungs could recover.

The discussions generally put cold water on the that transplants would be a viable remedy for acutely ill Covid-19 patients. But doctors wondered whether ECMO might create a cohort of patients with compromised lungs who will need a transplant a year or two down the line, putting a run on a scare resource.

ECMO itself is a scarce resource, and during a Zoom session last month, doctors debated the ethics of deciding which patients should be offered it, and how long they should be allowed to stay on the machine before someone waiting in line should get a chance. Older age and certain serious medical conditions were two considerations that pushed patients down the priority list for starting on ECMO, participants said.

Mass. General, for example, initially determined that patients with renal failure should be ruled out for ECMO, but when it turned out that a lot of very sick Covid-19 patients had renal failure, the hospital loosened that restriction, Yuval Raz, the hospital’s medical director for respiratory ECMO, told the group.  At one point, the hospital set a record for the number of patients on ECMO at one time and had to suspend use of the technology for 24 hours, he said.

“Obviously, it can be hard to stop ECMO once started,” added Emily Rubin, a pulmonologist and critical care specialist at the hospital. “But it can also be hard in a very emergent situation to sort things out in enough detail to deny access to begin with.”

Other doctors noted that the drain on staffing is a major concern with ECMO. In an interview, Advent Health’s Silvestry said if he has four Covid-19 patients on ECMO, he needs eight nurses to care for them. But it requires just two or three nurses to care for eight Covid-19 patients who don’t need the technology to survive.

One of his own recent cases underscores some of the ethical challenges. He got a call from a doctor in South Florida on a night in early July who had a 28-year-old Covid-19 patient who had just given birth via C-section, who had other children, and who desperately needed ECMO. He had called five other hospitals in South Florida; all were full.

“There was fear in his voice that he could do nothing else for this patient,” Silverstry said. His hospital had one bed left, but what was the hospital’s obligation if a patient from the Orlando area needed it? He called around to colleagues in Tampa and other hospitals in the state.

None was able to take the patient. So Silvestry sent a team to transport the patient to Orlando. She was hooked up to ECMO and quickly improved. Six days later, she was sent back where she could be with her baby, Silvestry said.

“Everybody was happy,” he added, but “there was no place for people who really needed extraordinary care.”

Future topics for the sessions are likely to include managing pregnant or immediately postpartum Covid-19 patients who may need ECMO like Silvestry’s, and whether earlier or less-invasive ECMO-style interventions might improve outcomes for patients.

Based on published reports and data presented during the sessions, Rame estimates the survival rate for Covid-19 patients put on ECMO is 55% to 60%. This is in line with a 55% survival estimate for Covid-19 patients on ECMO from a registry compiled by the Extracorporeal Life Support Organization, an Ann Arbor, Mich., group that has tracked ECMO outcomes for 30 years. Rame hopes that with more data published in journals and the help of the weekly Zooms, survival for Covid-19 patients will reach 60% to 70%. “Not bad,” he said, “given survival would have been zero.”

Mass. General’s Raz said what he learned from the French in the sessions helped his patients, while Raz’s experience in turn aided doctors at Penn and other centers. “Now places in Texas, Florida, and Arizona are able to gain information from what the hospitals in the Northeast went through,” he said.

All of which reflects a level of “collaboration between centers that did not exist before,” he added. “That’s the best thing coming out of these meetings and a silver lining for the Covid era.”

How a Zoom forum is changing the way ICU doctors treat desperately ill Covid-19 patients

California company’s better version of a simpler, faster Covid-19 test

In some parts of the U.S. right now, it can take weeks to get results for a simple Covid-19 test, a delay that renders the results largely useless.

So a handful of city governments and schools are turning to an entirely different type of Covid-19 test that they say is simpler, easier, and most importantly faster — and therefore more meaningful.

The tests are like a streamlined version of the far more common PCR tests used to diagnose Covid-19. The test’s simpler process requires fewer materials and less equipment; the results can be read by eye within an hour. But the technique — known as LAMP — can also, in some situations, be less sensitive and less accurate than PCR tests. And it can be hard to run many of the tests at once outside of a central laboratory; people can only work so quickly.

Enter Color Genomics, a California-based, genetic testing company that says it has solved many of the problems associated with the technique. Its Covid-19 tests are just as accurate as PCR tests, according to the documents it filed to the Food and Drug Administration for an emergency authorization. And it’s automated the process enough to run thousands of tests each day. Already, Color is processing about half of all the daily tests run in San Francisco and returning results in one to three days.

But Color’s improvements come with tradeoffs. Experts told STAT that an additional step in the company’s process means it costs more and takes more time than others. Color’s automation setup might not be cheap to replicate around the country. And since Color uses the same swabs and some of the same chemicals that so many PCR tests rely on, it could also face some of the same supply chain issues that have plagued other testing efforts.

“It opens up the flexibility of the supply chain to this PCR alternative, which is nice. But it doesn’t overcome some of the common barriers to testing,” said Matthew Lalli, a researcher studying genomics technologies at Washington University in St. Louis.

The technology behind the tests is known as LAMP, or loop-mediated isothermal amplification. It’s been around since the 1990s, when a Japanese scientist developed it as a less-intensive alternative to PCR, or polymerase chain reaction-based tests.

Both PCR-based and LAMP-based tests look for genetic strands of a given virus in a sample collected from a patient. But PCR requires that a sample be repeatedly heated up and cooled down in precise intervals using an expensive machine known as a thermocycler.

LAMP does not require a thermocycler. The reaction can be run at a constant temperature — about 65 or 70 degrees Celsius, or 150 degrees Fahrenheit. That makes it far simpler to run, and far less equipment-intensive. The reaction also creates a change in the acidity level of a sample; often, a compound that changes color from pink to yellow in different pH conditions is added to the tube, which means anyone can read the results.

Before this year, LAMP-based tests have been used for screening animal food for Salmonella as well as diagnosing C. difficile infections in humans and chlamydia in koalas.

And several groups around the world are developing new Covid-19 testing programs around LAMP. Many are relatively basic: In Racine, Wis., for example, researchers are running LAMP tests in an unused corner of city hall with minimal equipment and supplies, as Wired reported last month. Another Wisconsin group is running tests in elementary school parking lots. And a hospital in Germany is experimenting with a LAMP-based surveillance protocol developed at the Broad Institute.

But many of those point-of-care LAMP tests have an admitted shortcoming: Though they are simple, cheap, and fast, they are also less sensitive than PCR tests. Because of that, it’s often used for screening groups to try to catch most of the people who might have a disease — not to formally diagnose someone.

There’s a type of PCR, for example, that “has a nearly perfect sensitivity. You cannot beat that,” said Jonathan Schmid-Burgk, a professor at University Hospital Bonn who has also developed a test that relies on LAMP technology and who is not affiliated with Color.

Color’s LAMP-based tests solve that problem by adding a little complexity. Before Color actually runs the LAMP protocol on a swab, it extracts and purifies the RNA. This step, which is done on a particular machine that uses magnetic beads, concentrates the RNA.

“This [step] directly translates to sensitivity,” said Schmid-Burgk — that is, it can make it more likely that a test will give accurate negative results.

The company’s EUA paperwork indicates that for more than 500 samples, its test gave the same results as the Covid-19 diagnostic test developed by the Centers for Disease Control and Prevention.

Color’s been using the technology for Covid-19 tests since April; the company got the first-ever FDA emergency authorization for the test in May.

The 7-year-old company is far better known for selling genetic tests — work that investors and governments alike have been willing to fund. It raised $215 million from venture capitalists and received grants worth millions through the NIH’s All of Us program, which intended to sequence q million Americans’ genomes.

When the pandemic came to the U.S., Color expected that it would be helping labs figure out how to automate certain processes to take some of the human effort out of running Covid-19 tests.

“The deciding factor for us was the realization that no one we were talking to was taking an integrated approach similar to what had made us successful in genetics,” said Color spokesperson Benjamin Kobren. “Lab people were trying to build a lab. Logistics people were trying to set up drive-through sites, and so on.”

But in the early days of the pandemic, supplies to run PCR tests were in very short supply. Color’s team worried that competing with other labs for limited supplies might exacerbate the testing problem. So they looked at alternate protocols, like LAMP, that wouldn’t add stress to some of the PCR supply chains.

“The thing that made it good for point-of-care testing was actually the thing that we thought would make it really good for super high-throughput labs — which is that it’s a relatively simple process,” said Color’s CEO, Othman Laraki. “We’re able to run almost the entire process on a single robot.”

San Francisco’s city government began working with Color in early April, according to a spokesperson. Color is one of a handful of labs behind the CityTestSF program, which offers testing by appointment for San Francisco residents and essential workers. The company charges about $100 per test, a San Francisco city representative told STAT; that figure is about the same as Medicare’s current reimbursement rate for Covid-19 PCR tests.

Kobren, the company’s spokesman, noted that the price of a test can vary, depending on how many tests are included in a particular contract and what kind of group that contract covers.

Since the program began, Color says it has been able to deliver results far more quickly than many other laboratories. Results from Color are usually available within one to three days, the company’s website states.

That kind of turnaround time has been critical, said Sarah Owens, the deputy press director for San Francisco’s mayor.

“Effective contact tracing depends on Covid-19 results being received in a timely manner,” Owens said. Getting results back quickly “allows us to contact people who test positive and begin the process of reaching out to their close contacts more quickly, thereby slowing the spread of COVID-19 in the community.”

Color’s LAMP tests are also the foundation of the University of Southern California’s testing program; the company said in a press release that it expects to run at least 500 tests per day on samples collected at three different sites.

Experts caution Color’s test isn’t suddenly going to replace PCR tests around the country.

For one, its product is proprietary; only Color’s lab can process the tests, necessarily limiting how many can be run in a day. Color’s worked hard to increase the number — its automated process can now handle 10,000 tests per day.

That RNA purification step that Color added comes with a price.

“Purifying RNA is really tedious,” said Schmid-Burgk. Adding purification may increase a test’s sensitivity. However, it also increases the time a test needs to process and can ultimately cuts down on the number of tests a lab can process each day.

“You kind of lose the speed advantage by adding an RNA extraction step,” said Lalli, the Washington University in St. Louis researcher.

Color’s automated setup is also expensive. Replicating Color’s automation would require about $500,000 worth of equipment, according to Chris Mason, a computational genomics specialist at Weill Cornell Medicine.

Even existing clinical laboratories with deep pockets might hesitate before ordering equipment and supplies to set up an entirely new protocol when PCR machines are already sitting in their facilities.

“Most labs have PCR equipment, but many do not have LAMP, so it logistically makes it more difficult to bring up in the scale needed for widespread testing,” a Quest spokesperson noted.

Another potential challenge: While some parts of Color’s LAMP reaction uses machines and chemicals that are completely distinct from those needed for PCR tests, Color’s process still requires some of the same supplies — like swabs, RNA extraction kits and pipette tips.

The New York Times reported that those supplies may become scarce again soon — which means that even Color itself could ultimately be unable to use its lab’s full capacity or unable to process tests as quickly as it is now.

But Color’s team is optimistic that it’s prepared for that possibility. The company is hiring more people, adding additional equipment, and partnering with other labs that can run PCR tests in order to handle potential increases in demand. And Kobren, the company spokesman, told STAT that the company believes its automation “enables us to reduce per-test consumption of scarce resources such as pipette tips and tubes.”

“We continue to invest resources and R&D to make our processes as efficient as possible.”

This California company has a better version of a simpler, faster Covid-19 test

Vaccine for COVID-19 will need outside expert review – U.S. regulator

The United States will need to have independent experts review COVID-19 vaccine candidates before approval, the country’s top drug regulator said on Friday, offering reassurance that his agency would not cut corners in the race to roll out a vaccine.

U.S. Food and Drug Administration Commissioner Stephen Hahn said COVID-19 vaccine candidates will be reviewed according to established legal and regulatory standards for medical products, including by an outside advisory committee.

“Given the widespread potential use of a COVID-19 vaccine, transparent discussion at FDA’s Vaccines and Related Biological Products Advisory Committee will be needed…”, Hahn and colleagues wrote in the Journal of the American Medical Association. (bit.ly/3gEzyZ0)

The U.S. government’s Operation Warp Speed aims to expedite development of a vaccine and therapies to treat the novel coronavirus, and the emphasis on speed has provoked public anxiety about the safety and effectiveness of these vaccines, Hahn and the other officials wrote.

“There is a line separating the government’s efforts to focus resources and funding to scale vaccine development from FDA’s review processes, which are rooted in federal statute and established FDA regulations,” they added.

Earlier this week, the country’s infectious diseases chief, Anthony Fauci, told Reuters political pressure will not determine when a coronavirus vaccine is approved. At about the same time, U.S. President Donald Trump said it was possible for the country to have a coronavirus vaccine before the Nov. 3 election.

More than 159,000 people have died in the United States from COVID-19 and more than 4.89 million cases have been reported in the country and its territories, according to Reuters tallies.

https://www.reuters.com/article/us-health-coronavirus-vaccine/vaccine-for-covid-19-will-need-outside-expert-review-u-s-regulator-says-idUSKCN253307

Incyte/Morphosys take on CAR-Ts with $198,000 per year antibody

August 7, 2020

Incyte and Morphosys’ Monjuvi antibody therapy has been approved for certain patients with lymphoma, as the companies hope to provide a more convenient alternative to expensive and cumbersome CAR-T therapy.

At the beginning of the year Incyte paid $750m to Morphosys for the CD-19 targeting antibody, which has been approved in combination with BMS’ Revlimid (lenalidomide) for adults with relapsed or refractory diffuse large B-cell lymphoma not otherwise specified.

The indication also covers DLBCL arising from low grade lymphoma and patients not eligible for autologous stem cell transplant.

Monjuvi (tafasitamab) targets the CD-19, a protein on the surface of B-cells that is also targeted by Amgen’s bispecific antibody Blincyto (blinatumomab) for acute lymphoblastic leukaemia (ALL), as well as two CAR-T therapies – Novartis’ Kymriah (tisagenlecleucel) and Gilead’s Yescarta (axicabtagene ciloleucel) – that are already approved for DLBCL and other B-cell cancers.

Under the agreement with Morphosys the companies will co-market the drugs in the US, while Incyte has exclusive rights outside the US.

The deal with Morphosys could see Incyte pay up to $1.1 billion should certain targets be achieved.

Xencor, which developed the drug before licensing it to Morphosys in 2010, will receive a $25 million milestone payment and a royalty on worldwide net sales.

Before any rebates or discounts Monjuvi’s wholesale price will average $16,500 per month in the first year of therapy, followed by an average of $13,000 per month in subsequent years because of a decrease in the required number of doses per cycle.

At around $198,000 for the first year this is pricey but may work out as less expensive than CAR-Ts from Novartis and Gilead, depending on how long patients stay on treatment.

CAR-Ts cost $373,000 in adult DLBCL for a single shot of the cell therapy.

CAR-Ts can be highly effective, producing a complete response in about a third of patients, but are made by harvesting a patient’s own cells and modifying them to fight cancer – a lengthy process that might not appeal to all patients.

There are also dangerous side-effects with CAR-Ts, where doctors often have to manage “cytokine storms” where the immune system goes into overdrive and begins to attack a patient’s own body.

The FDA approval of Monjuvi was based on data from the MorphoSys-sponsored phase 2 L-MIND study, an open label, multicentre, single arm trial of Monjuvi in combination with lenalidomide as a treatment for adult patients with relapsed or refractory DLBCL.

Results from the study showed an overall response rate of 55%, including a complete response rate of 37% and a partial response rate of 18%.

Warnings and precautions for Monjuvi included infusion-related reactions, serious or severe myelosuppression (including neutropenia (50%), thrombocytopenia (18%), and anemia (7%)), infections (73%) and embryo-foetal toxicity. Neutropenia led to treatment discontinuation in 3.7% of patients.

This accelerated approval may depend on further confirmatory data from larger trials.

Incyte/Morphosys take on CAR-Ts with $198,000 per year antibody

Southern Mexico state bans junk food sales to children

Legislators in southern Mexico have approved a ban on selling high-calorie snack food to children, seeking to combat one of the world’s highest rates of childhood obesity.

A first of its kind in Mexico, the measure approved Wednesday by the Oaxaca state legislature would fine shopkeepers for selling or giving away high-calorie snack food like sodas, pastries or chips to anyone under 18, unless an accompanying parent or guardian authorized it.

The bill, which has to be signed by the Oaxaca governor to become law, also would ban vending machines from dispensing those same goods and prohibit their sale in or near schools.

Officials in Mexico have blamed junk food and soft drinks for Mexico’s high rate of deaths among middle-aged people from COVID-19, saying Mexicans die at younger ages from the pandemic in part because of the country’s high rates of diabetes and obesity.

The bill appears to try to skirt the sensitive issue of Oaxaca’s traditional snacks—the state produces chocolate—by defining the banned goods as “sugary drinks and packaged foods with high calorie content.” Most traditional Oaxaca snacks would apparently not be considered “packaged.”

The U.N. Children’s Fund considers childhood obesity to be a health emergency in Mexico, saying the country’s children have the highest consumption of junk food and many get 40% of their total caloric intake from it. A Mexican government health survey found that 75% of Mexican children were overweight or obese in 2018.

The National Association of Small Store Owners criticized the legislation Thursday, saying it could hurt 58,000 small shops, eateries and street stands and cause job losses in Oaxaca. It said the measure comes as 70,000 small stores across the country have been forced to shut by the coronavirus pandemic.

“History demonstrates that this kind of measure, instead of reducing consumption, increases it. Prohibition promotes informal sales, illegality and evasion, with absolutely no health safeguards,” the association’s president, Cuauhtémoc Rivera, said in a statement.

Mexico’s soft drink bottlers association and other business groups also warned of economic damage in Oaxaca, which is an impoverished state with a large Indigenous population.

Studies have shown that junk food is particularly popular in poor communities, because of its price and ubiquitous distribution, and especially damaging to some Indigenous people with a predisposition to developing diabetes.

State Rep. Magaly López Domínguez, the bill’s sponsor, stressed in an interview with the MVS radio station that “parents will have the freedom to choose. It will be they who decide what products they buy for their children to consume.”

Earlier this year, Mexico’s federal government announced it will require warning labels on high-calorie products, a move that had also was opposed by industry groups. The new rules will require black octagonal stop signs to be printed on the front of packages reading “high in calories,” “excessive salt” or “high in saturated fat,” among other things.

https://medicalxpress.com/news/2020-08-southern-mexico-state-junk-food.html