Results from Chinese drug trials for coronavirus due in weeks

Chinese scientists are testing two antiviral drugs against the new coronavirus and preliminary clinical trial results are weeks away, the co-chair of a World Health Organization (WHO) meeting said on Wednesday.

Dr. Marie-Paule Kieny, a former WHO virologist, co-chaired the two-day, closed-door research forum in Geneva of more than 300 scientists and researchers, including some who took part virtually from China and Taiwan.
“The Chinese colleagues are very eager to participate in protocols which are being defined so that all the clinical trials are done according to the same standards and are looking towards the same outcome,” she told a news conference. “They were very interested in working on such a master protocol.”
The coronavirus, now dubbed COVID-19, that emerged in central China in December has infected more than 44,000 people and killed over 1,100 in China and has spread to at least 24 other countries.

Kieny said quite a number of patients have already been dosed with a combination of the antiviral drugs ritonavir and lopinavir, but she did not have an exact count.
It “would be excellent if it would work because this drug is available in particular as a generic formulation for the treatment of HIV, so this would clearly be a drug that would be available,” Kieny said.
The combination HIV therapy is sold under the brand name Kaletra by AbbVie Inc (ABBV.N).
It remains to be seen whether the treatment will prove effective against the new virus, she said. “We don’t know the result, and we still have to wait for a few days, or a few weeks to have a result.”

A state-run Chinese research institute applied last week for a patent on the use of the experimental antiviral drug remdesivir from U.S.-based Gilead Sciences Inc (GILD.O), which scientists hope may be effective against the coronavirus.
“They will very soon start to dose patients on remdesivir … which had been tested without much success with Ebola, but Ebola virus and coronavirus are different and it may have a better success with corona,” Kieny said.
“But we will have to wait for a few weeks whether this gives any positive signal.”
https://www.reuters.com/article/us-china-health-who-drugs/results-from-chinese-drug-trials-for-coronavirus-due-in-weeks-expert-idUSKBN2062X3

Coronavirus outbreak begins to disrupt booming China drug trials

The fast-spreading coronavirus is starting to disrupt testing of experimental medicines in China, posing a threat to plans by global drugmakers that have invested billions of dollars to harness the potential of the Asian economic powerhouse.

The U.S. clinical trials database lists nearly 500 studies with a site in the city of Wuhan, which has endured the brunt of an outbreak that has killed more than 1,100 people and infected more than 44,000 in China. About 20% of global trials are now conducted in China, up from about 10% just five years ago, according to GlobalData Plc.
China has imposed a virtual lockdown on Wuhan and severely restricted travel in its wider province of Hubei and some other cities.
While it is too early in the outbreak first detected in December to fully assess its impact on clinical trials, if it goes on much longer the pharmaceutical industry’s China strategy is likely to be disrupted.
Virus-curbing efforts by the government have made it difficult for trial patients to reach hospitals running studies, according to interviews with two contract research organizations that conduct trials for drugmakers, local drug companies and doctors.
Others fear becoming infected if they return to a healthcare facility for a trial.
“Hospitals aren’t focused on clinical trials right now,” said Ian Woo, president and chief financial officer of Everest Medicines, which is developing drugs for the Chinese market. “They have plenty of other things to be focused on.”
The outbreak has delayed the launch of new studies, and research organizations like dMed Biopharmaceutical Co said they have been unable to send staff to monitor trial sites.

Affected ongoing studies include trials testing a Novartis medicine for a rare blood disorder, a cancer drug from BeiGene Ltd and a treatment for a type of spinal arthritis from Chinese drugmaker Tasly Pharmaceutical Group, according to doctors involved.
Beijing-based BeiGene, which has more than 20 trials ongoing in Wuhan, said it was working to minimize potential delays and disruptions, but that it was “too early to speculate on any specific impact on our clinical trial and commercial progress in China.”
Other drugmakers with trials in China, including Roche, Zai Lab Ltd and Hutchison China MediTech Ltd (Chi-Med), also said it was too soon to speculate on the outbreak’s consequences. But the impact is being felt.
Shenghao Tu, who is working on the Tasly clinical trial in Wuhan, said the study in his hospital has been suspended.
“This is a problem that (we) never encountered before,” Tu said.
The issue is not limited to Wuhan.
Two doctors testing the BeiGene cancer drug tislelizumab in Beijing and Guangzhou city said efforts to contain the virus have hampered patient enrollment and capacity.
Both their hospitals now require that each room hold only one patient to prevent cross-infection, reducing the number they can accommodate.

The delays are disrupting a booming, homegrown pharmaceutical industry China hopes will supply its domestic market and compete globally.

INTERNATIONAL INVESTMENT

International drugmakers including Britain-based AstraZeneca Plc, Swiss drugmaker Roche Holding, U.S. biotech Amgen Inc and Switzerland’s Novartis AG have made big investments, hoping to benefit from cheaper trial costs in China, access to large patient populations and the ability to identify new drugs for Asian markets.
Amgen last year agreed to pay $2.7 billion for a 20.5% stake in BeiGene to develop cancer drugs for the Chinese market. A few weeks later, BeiGene in November became the first drugmaker to receive U.S. approval for a cancer therapy based on trials conducted largely in China.
Amgen research chief David Reese said at the time BeiGene has built “one of the premier clinical trial platforms in China,” noting its strong relationships with trial investigators and regulators.
Deals and joint ventures between international companies and China-based biotechs surged to at least $10 billion in 2019, from about $3.2 billion in 2015, according to a Reuters analysis of GlobalData information.
(Graphic: China’s growing global drug development footprint, here)

BeiGene’s chief advisor Eric Hedrick sees the potential for more lucrative deals for his company.

“We think that there are other companies out there, like Amgen, who have the same sort of ambitions where BeiGene would make a good partner,” Hedrick said in an interview prior to the outbreak.

BETTING ON RESILIENCE

The surge in investment followed years of effort by Chinese regulators to elevate healthcare facilities to match global standards and increase the role China-run trials play in U.S. and European drug approval decisions.
Brad Loncar, chief executive of Loncar Investments who created a fund that tracks the Chinese pharmaceutical industry, said the epidemic could delay deals in the short run.
Longer term, investors expect the outbreak will prompt China “to accelerate its plans to really modernize its drug and healthcare sector,” he said.
Amgen said it had not yet seen disruptions to BeiGene operations. Novartis said it was monitoring the situation and would handle any disruptions. Tasly declined comment.
Much will depend on how long the outbreak lasts, particularly for trials set to begin later this year and ongoing studies that will take years to complete.
Chi-Med Chief Executive Christian Hogg was optimistic about a resolution. “This a relatively new phenomenon … and China is a resourceful country,” he said.
Roche, which last year opened a drug development center in Shanghai, sees China as key to its strategy to get new treatments to the global market.
“You can imagine the large number of patients (in China),” Jing He, head of Roche’s Shanghai pharmaceutical development center, told Reuters. “We will be able to enroll patients faster.”
For now, that may not be the case.
A doctor working on a study of Novartis’ eltrombopag for severe aplastic anemia who asked to remain anonymous because he is not authorized to speak with media, told Reuters the trial could be slowed due to patient recruiting obstacles. Some patients are not allowed to travel from their cities to qualified hospitals for required screening procedures, he said.
https://www.reuters.com/article/us-china-health-clinicaltrials-focus/coronavirus-outbreak-begins-to-disrupt-booming-china-drug-trials-idUSKBN2062IS

Welltower 2020 guidance midpoint trails consensus

Welltower (NYSE:WELL) sees 2020 normalized FFO per share of $4.20-$4.30 (midpoint $4.25) vs. consensus of $4.29.

Assumes 2020 average blended same-store net operating income of 1.5%-2.5%.

Q4 normalized FFO per share of $1.05 matches the consensus estimate and rises from $1.01 in the year-ago quarter.

Q4 total revenue of $1.26B exceeds $1.25B consensus and increased from $1.24B a year ago.

Q4 total portfolio same-store NOI rose by 2.2%, with consistent performance across all property types.

Completed more than $1.4B of pro rata gross investments comprised of $1.1B of acquisitions at a blended year one yield of 5.3% and expected stabilized yield of 5.6%; additionally, completed $308M of development funding with an expected stabilized yield of 7.9%.

Conference call on Feb. 13 at 9:00 AM ET.

Previously: Welltower FFO in-line, beats on revenue (Feb. 12)

https://seekingalpha.com/news/3541424-welltower-2020-guidance-midpoint-trails-consensus

Scientists find ally in fight against brain tumors: Ebola

Glioblastomas are relentless, hard-to-treat, and often lethal brain tumors. Yale scientists have enlisted a most unlikely ally in efforts to treat this form of cancer—elements of the Ebola virus.

“The irony is that one of the world’s deadliest viruses may be useful in treating one of the deadliest of brain cancers,” said Yale’s Anthony van den Pol, professor of neurosurgery, who describes the Yale efforts Feb. 12 in the Journal of Virology.
The approach takes advantage of a weakness in most cancer tumors and also of an Ebola defense against the immune system response to pathogens.
Unlike normal cells, a large percentage of cancer cells lack the ability to generate an innate immune response against invaders such as viruses. This has led cancer researchers to explore the use of viruses to combat a variety of cancers.
Using viruses carries an obvious risk—they can introduce potentially dangerous infections. To get around this problem, scientists, including van den Pol, have experimented with creating or testing chimeric viruses, or a combination of genes from multiple viruses. They have the ability to target cancer cells without harming patients.
One of the seven genes of the Ebola virus that helps it avoid an immune system response also contributes to its lethality. This intrigued van den Pol.
He and the study’s first author, Xue Zhang, also of Yale, used a chimeric virus containing one of gene from the Ebola virus—a glycoprotein with a mucin-line domain (MLD). In wild-type Ebola virus, the MLD plays a role in hiding Ebola from the immune system. They injected this chimeric virus into the brains of mice with glioblastoma—and found that the MLD helped selectively target and kill deadly glioblastoma brain tumors.
(The team worked with the MLD glycoprotein, not with the full Ebola virus.)
Van den Pol said MLD’s beneficial effect appears to be that it protects normal cells from infection—but not cancer cells, which lack the ability to mount an immune response to pathogens.
A key factor may be that the virus with the glycoprotein MLD replicates less rapidly, potentially making it safer than viruses without the MLD part of the glycoprotein, he said.
In theory, such a virus might be used in conjunction with surgery to eliminate glioblastoma tumors and help prevent a recurrence of cancer, he said.

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Explore further

Brain tumors may be new targets of Ebola-like virus

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More information: Xue Zhang et al, Mucin-like domain of Ebola virus glycoprotein enhances selective oncolytic actions against brain tumors, Journal of Virology (2020). DOI: 10.1128/JVI.01967-19

https://medicalxpress.com/news/2020-02-scientists-ally-brain-tumors-ebola.html

Treating Sleep Problems in Children With Autism

Identify whether sleep problems in children with autism spectrum disorder (ASD) may be caused by medication or other medical conditions and if so, address these factors, say new recommendations issued this week from the American Academy of Neurology (AAN).
If insomnia and disrupted sleep appear to be more behavioral in nature, a number of strategies may be effective for children and adolescents with autism, advised Ashura Williams Buckley, MD, of the National Institute of Mental Health in Bethesda, Maryland, and co-authors, in a practice guideline published in Neurology.
Up to 40% of children and teens in the general population have sleep problems at some point during childhood, but these typically diminish with age, noted Williams Buckley. But for children and teens with autism, “sleep problems are more common and more likely to persist, resulting in poor health and poor quality of life,” she said in a statement.
While autism symptoms may exacerbate sleep problems, the opposite also may be true, she pointed out. “Sleep problems can make behavioral issues in children and teens with autism even worse,” she said. “That’s why it is important for parents and caregivers to work with healthcare providers to find a way to improve a child’s sleep because we know that good quality sleep can improve overall health and quality of life in all children.”
To develop the guidance, panel members conducted a systematic review of studies about sleep disturbance in children with autism published through December 2017. The review showed a “dearth of evidence-based treatments” for sleep dysregulation in autism, the panelists noted.
Of 1,987 abstracts, 139 were potentially relevant, and 12 met criteria for data extraction. Eight studies were rated Class III or higher and were included in the panel’s review. None examined drug approaches like antidepressants, alpha-adrenergic agonists, benzodiazepines, anti-seizure medicines, or antipsychotics.
Recommendations
The AAN panel’s first recommendation was for healthcare providers to determine whether medications or co-existing conditions underlie sleep problems, and if so, to address them. This is especially important because children with autism have an increased risk of conditions that could contribute to sleep disturbance, such as apnea, epilepsy, depression, anxiety, bipolar disorder, ADHD, and gastrointestinal illness.
The guideline writers also advised clinicians to counsel parents about behavioral strategies, including:

• Setting up a consistent sleep routine with regular bedtimes and wake times
• Developing and adhering to pre-bed calming rituals
• Choosing a bedtime close to the time a child begins to fall asleep

“Behavior-modification strategies are a good place to start because they do not cost anything, there are no side effects, and they have been shown to work for some people,” Williams Buckley pointed out. Family-based cognitive behavioral therapy also may improve aspects of sleep.
If behavioral strategies are not helpful and contributing conditions and medications have been addressed, clinicians should offer melatonin, starting with a low dose. They should advise patients to use a pharmaceutical-grade preparation, if possible. Melatonin is the most commonly dispensed hypnotic drug in children, but melatonin concentrations in over-the-counter formulations differ and some formulations are contaminated with other products like serotonin, they cautioned.
No insomnia drugs are FDA-approved for pediatric use, the guideline authors noted.
Clinicians should counsel patients and parents that melatonin may have adverse effects like morning drowsiness, increased enuresis, headache, or dizziness, and should let them know long-term safety information is lacking.
“Given that many children with ASD use melatonin for months or years, the lack of long-term safety data is concerning,” the authors wrote. “Melatonin affects the hypothalamic–gonadal axis and can potentially influence pubertal development.”
Melatonin alone may be just as helpful for some patients as combining melatonin with behavioral strategies, they added.
Panel members found no evidence that weighted blankets or special mattress technologies improve sleep when used routinely. “If asked about weighted blankets, clinicians should counsel that the trial reported no serious adverse events with blanket use and that blankets could be a reasonable nonpharmacologic approach for some individuals,” they wrote.
Future research is needed about the long-term use of melatonin and about children with ASD and concomitant mood disorders, the authors noted. “Research tying the underlying neurobiology in early-life sleep disruption to behavior might help clinicians and researchers understand which treatments might work for which people with ASD,” they added.

Disclosures

This document was developed with financial support from the American Academy of Neurology.
Authors listed numerous relationships with government agencies, publishing companies, academic centers, and industry.

Primary Source

Neurology

Source Reference: Williams Buckley A, et al “Practice guideline: Treatment for insomnia and disrupted sleep behavior in children and adolescents with autism spectrum disorder Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology” Neurology 2020; DOI: 10.1212/WNL.0000000000009033.

https://www.medpagetoday.com/neurology/autism/84852

Lilly and Novo Nordisk Question FDA’s Draft Guidance on Insulin Biosimilars

In November 2019, the U.S. Food and Drug Administration (FDA) released new draft guidance that would help generic drug companies bring biosimilars to insulin to the market more quickly. And now there are reports that two of the three primary biopharma companies that sell insulin in the U.S. are trying to change that draft guidance.
The key focus of the eight-page draft guidance suggested eliminating the need for comparative clinical immunogenicity studies for potential insulin biosimilars under specific situations. A biosimilar is a generic version of a biologic drug, but because it is not a direct copycat, but is instead “similar,” has to undergo a regulatory pathway very similar to that of branded drugs.
The FDA’s rationale was scientific research suggesting a “lack of clinical impact of immunogenicity with insulin,” and notes that the European Medicines Agency (EMA) made the same recommendation in 2015.
The FDA also stated that there were “decades of clinical experience with approved insulin products, including the lack of a correlation between immunogenicity and safety or effectiveness as reflected in approved product labeling for insulin products.”
The draft guidance was then open for comments from the industry. On January 28, 2020, Novo Nordisk said it had “experienced a circumstance of unexpected immunogenicity in response to a new insulin analog which was encountered during its clinical development.”
It went on to say that this “exemplifies the unpredictable nature of immunogenic reactions in response to insulin formulations. As such, we believe caution needs to be applied regarding the broad assumption” in the draft guidance that argues that “if a comparative analytical assessment based on state-of-the-art technology supports a demonstration of ‘highly similar’ for a proposed biosimilar or interchangeable insulin product, there would be little or no residual uncertainty regarding immunogenicity.”
Eli Lilly argues the FDA should revise the guidance to be more specific about where this immunogenicity testing is applied and when.
“Should FDA intend to apply the Draft Guidance to insulin products which were not approved under a section 505(b)(2) application, Lilly believes that good science dictates some amount of clinical immunogenicity data should be required in order to understand the impact of potential differences in immunogenicity profiles on clinical outcomes,” Lilly stated.
The other big company in the insulins market is Paris-based Sanofi, which did not comment on the draft guidance.
Both companies have been under fire for the price and availability of insulin. In January 2020, Lilly added another lower-priced version of its insulin products to the market in response to the criticism. It is offering cheaper versions of Humalog Mix75/25 KwikPen (insulin lispro protamine and insulin lispro injectable suspension 100 units/mL) and Humalog Junior KwikPen (insulin lispro injection 100 units/mL).
Both will be marked down 50% compared to the branded versions and be made available by mid-April. They are identical to the branded versions and may be substituted at the pharmacy.
This was Lilly’s second attempt at introducing lower-cost insulins. In May 2019, two months after regulatory approval, the company’s authorized generic formulation of Humalog went on sale at a 50% lower price than its branded form of insulin. However, an August analysis indicated patients weren’t getting the cheaper version, partly because of lack of awareness of the product.
All three insulin companies have raised insulin prices significantly over the last 10 years. In 2012, a vial of Lilly’s Humalog went for $130 and in 2016, the price was $255.
Novo Nordisk also launched authorized generics of its insulin products at decreased prices, partly in preparation for biosimilar competition.
https://www.biospace.com/article/lilly-and-novo-nordisk-question-fda-s-draft-guidance-on-insulin-biosimilars/

CVS Swings to Profit, Forecasts 2020 Results in Line With Estimates

CVS Health Corp. turned a profit that beat Wall Street expectations and projected results for 2020 that matched estimates, as it capped its first year of integrating health insurer Aetna Inc.’s operations.
The earnings continued a string of quarters that mark a recovery from a year ago, when CVS’s shares dropped sharply after it offered lackluster 2019 guidance. Shares of CVS rose slightly in trading Wednesday morning on the New York Stock Exchange.
The company also said that the head of its pharmacy-benefits unit, Derica Rice, will leave. His exit comes after the departure earlier this year of Kevin Hourican, the leader of the pharmacy operations, who left to take a CEO job elsewhere.
CVS said Alan Lotvin, currently an executive vice president, will take over the PBM. The company previously said that chief operating officer Jonathan Roberts would temporarily lead the pharmacy unit.
CVS said during a conference call with analysts and investors that it is seeing benefits from its nearly $70 billion takeover of Aetna, which closed in late 2018.
“We have set a clear and bold path for CVS Health to be the most consumer-centric health company, transforming the way care is delivered in the U.S.,” CVS Chief Executive Larry Merlo said. “With over a year of successful integration, we have laid a strong foundation for growth.”
Former Aetna Chief Executive Mark Bertolini, who recently resigned from CVS’s board after publicly saying he was being pushed out, told The Wall Street Journal the integration of the two companies was far from complete.
For 2020, CVS expects per-share earnings from continuing operations of $5.47 to $5.60, or $7.04 to $7.17 on an adjusted basis. It sees operating income of $12.8 billion to $13 billion, or $15.5 billion to $15.8 billion on an adjusted basis.
Analysts polled by FactSet have projected 2020 earnings per share of $5.52, or $7.15 on an adjusted basis.
CVS reported fourth-quarter net income of $1.75 billion, or $1.33 a share, compared with a loss of $419 million, or 37 cents a share, in the comparable quarter a year before. Adjusted earnings were $1.73 a share.
Analysts were looking for earnings of $1.22 a share, or $1.68 a share on an adjusted basis.
CVS said its revenue rose 22.9% to $66.89 billion from the same period the year before as revenue from premiums shot up. Analysts were targeting $63.93 billion.
Revenue in its retail segment, which fulfills prescription medications and sells a range of merchandise, was $22.58 billion, up from $22.03 billion in the year-earlier period. Like competitor Walgreens Boots Alliance Inc., CVS faces pressure on margins in its retail-pharmacy business.
Mr. Merlo said the company’s health-hub stores, which offer a broader array of health services than its traditional pharmacies, are showing higher prescription volume and front-store sales in line with expectations. Yet he didn’t offer financial details on their performance. He said the company would share more information later this year.
CVS is in the process of rolling out around 1,500 of the new stores, which target people with chronic conditions such as diabetes with testing, monitoring and treatment plans.
The company’s health-care benefits business, which includes Aetna, posted revenue of $17.15 billion, up nearly threefold from the prior year. The segment’s medical-loss ratio, which represents the share of premiums paid out in claims, was 85.7% for the quarter.

https://www.marketscreener.com/CVS-HEALTH-CORPORATION-12230/news/CVS-Swings-to-Profit-Forecasts-2020-Results-in-Line-With-Estimates-Update-29987217/