COVID-19 may damage bone marrow immune cells; another reinfection reported

By Nancy Lapid

(Reuters) – The following is a roundup of some of the latest scientific studies on the novel coronavirus and efforts to find treatments and vaccines for COVID-19, the illness caused by the virus.

COVID-19 may damage immune cells in the bone marrow

Even bone marrow may not be a safe harbor from the ravages of COVID-19, according to a study that found previously unrecognized changes in newly produced immune cells, called monocytes, released into the blood from bone marrow. To learn more about how the body responds to COVID-19, researchers obtained serial “snapshots” of patients’ immune health by analyzing their immune cells at multiple points during their hospital stays. In COVID-19 patients with more severe disease, the monocytes do not function properly, researchers reported last week in Science Immunology. It was not yet clear whether the monocytes are being released from the bone marrow in an altered state or whether the alterations happen after monocytes enter the blood, coauthor Tracy Hussell of the University of Manchester in the UK told Reuters. Either way, she said, treatments that prevent their release from the bone marrow may help reduce the exaggerated immune response that contributes to poor outcomes in patients with severe COVID-19.

COVID-19 reinfections occur, but remain rare

Another case of reinfection after recovery from COVID-19 has been reported, this time in a healthy young military healthcare provider at a U.S. Department of Defense hospital in Virginia. He was first infected by a patient in March. He recovered within 10 days and “returned … to excellent health,” his doctors reported on Saturday in Clinical Infectious Diseases. Fifty-one days later, he was reinfected by a household member. Genetic studies showed the first and second infections to be from slightly different strains of the virus. The reinfection made him sicker, perhaps because the second strain was more potent, or the household contact infected him with a higher load of virus, doctors said. It was also possible antibodies from the first infection may have triggered his immune system to respond more strongly to the virus the second time his body encountered it. COVID-19 reinfections are still rare, they said. Kristian Anderson, professor of immunology and microbiology at Scripps Research in La Jolla, California, recently told Reuters virus reinfections are always possible. “We don’t know at what frequency reinfections (with the new coronavirus) occur and how that might change over time,” Anderson said. Without further studies, “we can’t conclude what a single case of reinfection means for longevity and robustness of COVID-19 immunity and relevance for a future vaccine,” she added.

Proven immunotherapy approach might be possible in COVID-19

A proven approach to severe virus infections, known as cytotoxic T cell therapy, may be applicable to COVID-19 despite a potential hurdle, researchers said. The approach involves treating critically ill patients with infusions of key immune cells known as T-lymphocytes obtained from people who successfully fought off the same virus. These donor T cells have learned to recognize and target the invading virus. But steroids, which are being increasingly used to treat COVID-19 patients, are toxic to lymphocytes, likely canceling out any beneficial effects of the immunotherapy. In a new report posted on bioRxiv ahead of peer review, researchers describe a possible workaround. They say they have figured out a way to take donor T cells that target the novel coronavirus and make them resistant to the deadly effects of steroids. “We are currently working on … developing clinical trials to determine safety and efficacy,” coauthor Dr. Katy Rezvani of The University of Texas MD Anderson Cancer Center told Reuters.

High COVID-19 mortality seen in assisted-living facilities

Data compiled from more than 4,600 assisted living facilities in seven U.S. states through the end of May showed a four-fold higher COVID-19 fatality rate than in the nearby communities, researchers reported on Monday in the Journal of the American Geriatric Society. In North Carolina and Connecticut, for example, the proportions of COVID-19 cases that were fatal across the state were 3.3% and 9.3%, respectively. In assisted living facilities in those states, the fatality rate climbed to 13% and 31.6%. Unlike nursing homes, assisted living communities are not subject to federal regulation and are not required to collect and report data on COVID-19, coauthor Helena Temkin-Greener of the University of Rochester School of Medicine & Dentistry said in a news release. In this study, and in a separate study of nursing homes her team published on Monday in the same journal, COVID-19 cases were more common in facilities with more minority residents and more residents with dementia, chronic obstructive pulmonary disease, and obesity. “Assisted living communities and their residents urgently need local, state, and the federal governments to pay at least the same level of attention as that given to nursing homes,” Temkin-Greener and colleagues conclude.

(Reporting by Nancy Lapid and Deena Beasley; Editing by Bill Berkrot)

Gilead bolsters cancer portfolio with $21 billion acquisition of Immunomedics

(Reuters) – Gilead Sciences Inc will acquire biotech company Immunomedics Inc for $21 billion, a move that will strengthen its cancer portfolio by gaining access to a promising drug, the two companies said in a joint statement on Sunday.

The deal will give Gilead access to Immunomedics’ breast cancer treatment drug Trodelvy, which was granted an accelerated FDA approval in April for an aggressive and tough to treat type of breast cancer.

Gilead said it would issue a tender offer to buy all the outstanding shares of Immunomedics for $88 per share, representing a premium of about 108% over their last closing price of $42.25 on Friday.

“This acquisition represents significant progress in Gilead’s work to build a strong and diverse oncology portfolio,” Gilead Chief Executive Officer Daniel O’Day said in a statement. “Trodelvy is an approved, transformational medicine for a form of cancer that is particularly challenging to treat. We will now continue to explore its potential to treat many other types of cancer.”

Immunomedics is also on track to file for regulatory approval for Trodelvy in Europe in the first half of 2021, according to the statement.

The deal – and a separate transaction between Merck & Co and Seattle Genetics’s announced on Monday – was a sign of renewed confidence in an approach in oncology to pair antibodies with toxic agents to fight cancer.

Immunomedics’ Trodelvy is a so-called antibody-drug conjugates, or ADC, a class described by researchers as “guided missiles” that zero in on tumors to release cytotoxins that deliver up to 10,000 times the potency of standard chemotherapy, while minimizing damage to healthy tissue.

Merck, for its part, struck a deal with Seattle Genetics worth up to $4.2 billion, comprising stock purchases, an upfront payment and milestone rewards, to collaborate with the partner on two ADCs against breast cancer and other tumors.

In previous landmark deals for the field, AstraZeneca last year committed up to $7 billion for rights to Daiichi Sankyo’s Enhertu, another breast-cancer targeted ADC. It followed up in July with a deal worth up to $6 billion for DS-1062, another ADC developed by the Japanese drugmaker.

Trodelvy targets triple-negative breast cancer that has spread to other organs. Both aggressive and tough to treat, those tumor types account for 15-20% of breast cancers, lacking three genetic characteristics for which there are more treatment options.

Cancer immunotherapy Tecentriq by Gilead CEO O’Day’s former employer Roche has emerged as a new treatment option for this patient group.

Gilead’s offer will be funded with $15 billion in cash on hand, and through $6 billion in newly issued debt, according to the drugmaker.

The transaction is expected to close in the fourth quarter of 2020, the companies said.

The acquisition of Immunomedics is the latest of the several Gilead inked this year with the aim of expanding its oncology portfolio.

It bought a 49.9% stake in cancer drug developer Pionyr Immunotherapeutics in June for $275 million, just months after paying $4.9 billion for Forty Seven Inc, maker of an experimental treatment that targets blood cancer.

(Reporting by Ann Maria Shibu in Bengaluru and Ludwig Burger in Frankfurt; Editing by Peter Cooney, Diane Craft and Susan Fenton)

Too many cancer drugs? Crowded market gives investors pause

FILE PHOTO: A scientist prepares protein samples for analysis in a lab at the Institute of Cancer Research in Sutton, July 15, 2013. REUTERS/Stefan Wermuth/File Photo

By Ben Hirschler

LONDON (Reuters) – In London’s world-famous Great Ormond Street children’s hospital, Dr. Karin Straathof is excited about a new cell-based medicine that offers hope for toddlers with incurable nerve tissue cancer.

Her progress with a handful of children for whom standard care does not work reveals the promise of modern cancer drugs, an increasingly crowded pharmaceuticals field from which investors must try to select future winners.

The new therapy using engineered white blood cells has shown anti-tumor activity in the hardest to treat neuroblastoma patients.

“The beauty is that it is very specific in targeting the cancer cells, while leaving healthy tissue unharmed,” Straathof told Reuters, after presenting her early findings at a science meeting in Chicago in April. “It’s an important step forward.”

Autolus – the small British biotech company developing the chimeric antigen receptor T-cell or CAR-T treatment – is equally excited, and is planning a potential IPO on Nasdaq.

But Autolus is far from alone in pursuing CAR-T therapy. In fact, CAR-T treatment – part of the wider field of cancer immunotherapy – is one of the hottest areas of drug research today, with multiple firms piling in.

The biotech dollars are flooding in not only in Europe and the United States but also in China which, with 162 clinical trials, now boasts more CAR-T studies than the United States, according to a Reuters analysis of the latest data.

With over 2,000 drugs in the cancer immunotherapy space, the competitive landscape has never been more crowded as each firm seeks its own proprietary version of often similar drugs.

Overall, researchers are working on more than 5,200 cancer drugs, up 7.6 percent from a year ago, according to the Pharmaprojects database. The sheer number is stretching the ability of scientists to find enough patients to test them on.

Cancer now makes up 34.1 percent of the total drug industry pipeline, up from 26.8 percent in 2010, as companies divert resources into a promising sector where new treatments can often fetch more than $100,000 a year.


With the first two CAR-T treatments from Novartis and Gilead Sciences winning U.S. approval last year for rare blood cancers, the promise of such smart medicine is real and life-changing – especially if it can be made to work in solid tumors, as Straathof’s work suggests is possible.

However, the wholesale rush by pharmaceutical and biotech companies into the cancer area poses a dilemma for investors.

A flood of similar products makes it hard for investors to pick those companies that will achieve commercial success.

“More competition means you should be more circumspect,” said Nooman Haque, head of life sciences at Silicon Valley Bank in London, which provides financing for start-ups and venture capitalists.

“The traditional investment thesis in biotech is to have a differentiated medicine with not many competitors, which helps drive value. Here the problem is that even if there is a big patient benefit, there are questions as to how long your advantage lasts and what your commercial edge will be.”

Pharmaceutical executives are not blind to the issue, although each hopes to find a winning formula in immunotherapy – the fastest-growing part of the $100 billion-a-year cancer drug market, with sales expected to top $25 billion by 2021, according to analyst forecasts compiled by Thomson Reuters.

Roche <ROG.S> CEO Severin Schwan, head of the world’s top cancer company, says he expects “an enormous drop-out”, while Sanofi’s  outgoing research head Elias Zerhouni warned analysts last week that duplication of effort would shrink the time available for drugmakers to recoup their  investments.

“The cycle of innovation has been shortened significantly,” agrees Aiman Shalabi, chief medical officer at the non-profit Cancer Research Institute. “There is no doubt we are seeing fast follow-on and many identical agents hitting the same targets.”

The good news for society is that patients will find out much faster than in the past if new approaches work. But that means doctors can rapidly switch to alternatives, leading to increased product churn and uncertainty over future sales.


Twenty years ago, when Roche launched its state-of-the-art cancer drugs Herceptin and Rituxan, it enjoyed years without rivals. Today, there are multiple versions of new drugs targeting molecular pathways with acronyms such as PD-1/L1, PARP and CDK, as well as CAR-T.

“You’re either first or you’re best or you’re nowhere because it has become such a race,” said Paul Major, an investment manager at BB Healthcare Trust, who is cautious about investing in cancer immunotherapy.

Lydia Haueter at Pictet Asset Management is also wary, pointing out there are already five PD-1/L1 drugs on the market – from Merck, Bristol-Myers Squibb, Roche, AstraZeneca and Pfizer – and more are coming.

“It seems everybody has a PD-1, so we especially don’t go for those kind of cancer companies,” she said.

Some drugmakers like GlaxoSmithKline <GSK.L> and Novartis that missed the initial PD-1/L1 wave are trying to make a virtue of looking ahead to the next phase of cancer immunotherapy, particularly drug combinations.

Yet last month’s failure of a combination study using a next-generation drug from Incyte with Merck’s PD-1 Keytruda shows that adding a new agent is no slam dunk for expanding the reach of immune-boosting medicine.

At Great Ormond Street, Straathof is less concerned about doubling up on research and more focused on getting effective, affordable cures – and she hopes automated processes will eventually bring down today’s sky-high drug prices.

“I’m not too worried about duplication. It’s important to not ask the same question in two trials but I think there are a lot of questions to be addressed because there is a lot of nuance in the system.”

(Reporting by Ben Hirschler; Editing by Pravin Char)