Nonalcoholic Liver Disease ‘an Epidemic of the 21st Century’

The way Christos S. Mantzoros, MD, DSc, PhD, sees it, nonalcoholic steatohepatitis (NASH) is an epidemic of the 21st century that can trigger a cascade of reactions.
“If more than 5.8% of fat is in the liver, we call it nonalcoholic fatty liver disease [NAFLD],” Dr. Mantzoros, professor of medicine at Harvard Medical School, Boston, and Boston University, explained at the World Congress on Insulin Resistance, Diabetes, and Cardiovascular Disease. “If inflammation develops to remove the fat, we call it NASH. If this progresses to decompensated reaction and fibrosis and cirrhosis, then we call it nonalcoholic steatohepatitis with fibrosis. That can lead to liver cirrhosis, hepatocellular carcinoma, and liver failure.”
The underlying problem stems from the rise in obesity prevalence, according to Dr. Mantzoros, who is also chief of endocrinology at the Boston Veterans Affairs Healthcare System. For 75%-80% of individuals with metabolically unhealthy obesity, the storage space in their adipose tissue is exceeded. “Fat is deposited into muscle, causing insulin resistance, and into the liver,” he explained. “If it’s more than 5.8%, it causes NAFLD. Most of us don’t realize that most of the patients with diabetes we have in our clinics also have nonalcoholic fatty liver disease. That’s because we don’t have an easy diagnostic tool or an easy treatment. It’s an unmet clinical need.” (There are currently no drugs approved for the treatment of NASH or NAFLD. Current recommended first-line treatment is weight loss through diet and exercise and control of diabetes, if it is present.)
“Assuming the rate of increase in cost due to NAFLD parallels the growth in obesity, the 10-year projection for direct cost is $1.005 trillion,” said Dr. Mantzoros, who is also editor in chief of the journal Metabolism. “Obesity, NAFLD, and insulin resistance are each independently associated with a twofold risk for diabetes. If all three are present, there is a 14-fold risk for diabetes. Insulin resistance promotes an increase in free fatty acid traffic to the liver, which can trigger hepatic lipotoxicity. Hyperinsulinemia enhances free fatty acid uptake and activates de novo lipogenesis. Hyperglycemia can also activate de novo lipogenesis.”

About 85 million Americans have NAFLD, he continued. Most (80%) are cases of steatosis, but 20% have NASH. Of those, 20% develop advanced fibrosis, which leads to liver failure and transplantation or death. A study of data from the National Health and Nutrition Examination Survey found that diabetes was the strongest predictor of advanced fibrosis in patients with NAFLD (odds ratio, 18.20), followed by a body mass index of 30 kg/m² or greater (OR, 9.10), hypertension (OR, 1.20), and age (OR, 1.08; Ailment Pharmacol Ther. 2017;46:974-80). “Most of the patients who come to our clinics with diabetes have nonalcoholic fatty liver disease – 75%-80% in our clinics, and about 10% have advanced fibrosis,” Dr. Mantzoros said. “Most of them go undiagnosed.”
Patients with type 2 diabetes and NAFLD progress faster to fibrosis and end-stage liver disease, compared with those who do not have diabetes. One study of 108 patients with biopsy-proven NALFD showed that 84% of those with fibrosis progression had type 2 diabetes (J Hepatol. 2015;62:1148-55). Other findings have shown that patients with type 2 diabetes are at increased risk of chronic NAFLD and hepatocellular carcinoma (Gastroenterol. 2001;126:460-8). “We are doing more liver transplantations because of NAFLD and NASH than because of hepatitis C,” Dr. Mantzoros said. “What we need to keep in mind is that, although liver morbidity and mortality is important, this is a component of the cardiometabolic syndrome. So, people have all the risk factors for cardiovascular disease. Because CVD is much more common, people with NAFLD suffer from and die from CVD. The more advanced the NAFLD, the higher the risk of death from cardiovascular disease.”
https://www.medscape.com/viewarticle/924818

Puma Bio shorts squeezed?

Two factors may be behind this abrupt, double-digit uptick in Puma’s stock today. First, the biotech has consistently been one of the most heavily shorted equities in the industry over the prior 12 months. Short-sellers have piled on to this name due to the worrisome side effects associated with the company’s breast cancer drug, Nerlynx. Although Nerlynx is targeting a fairly large commercial opportunity, it has also seen an alarmingly high discontinuation rate due to severe diarrhea. This noteworthy pop, in turn, could be nothing more than a bout of covering on the part of one or more short-sellers.
Second, Puma may be fetching some takeover interest — which short-sellers might have caught wind of before the general public. Several big biopharmas have already announced plans this year to boost their pipelines through merger and acquisition activity, after all. Puma, for its part, might be an especially attractive target, given that its shares are trading at a small fraction of Nerlynx’s commercial potential.

Should investors jump on this surging biotech stock today? Unfortunately, the answer is probably not. Stated bluntly, Puma’s shares could quickly give back these impressive gains due to the lack of a clear-cut catalyst. And that’s simply not an attractive setup for long-term investors.
https://www.fool.com/investing/2020/02/05/why-puma-biotechnology-is-soaring-today.aspx

UPS reaches deal with pilots on flying to China

The UPS (NYSE:UPS) pilots union says it reached an agreement with the company for pilots to make a voluntary decision on whether they will fly to China or not.

“This joint effort addresses crewmember concerns over safety during the coronavirus health crisis,” reads a statement from the union.

Shares of UPS are down 9.0% over the last month.

https://seekingalpha.com/news/3538745-ups-reaches-deal-pilots-on-flying-to-china

NEJM Coronavirus Transmission Research Questioned

Asymptomatic transmission of the novel coronavirus in Germany was called into doubt on Monday when an article appeared to question the research behind it.
Science magazine detailed errors in the New England Journal of Medicine (NEJM) research letter published last Thursday. The letter reported that asymptomatic transmission of novel coronavirus occurred in Bavaria, Germany, when several co-workers of an asymptomatic woman traveling from China contracted the virus.

The letter, and several media reports, said that the woman wasn’t sick when she was in Germany and only began to feel ill on the plane ride home. Turns out that wasn’t quite true.
Researchers who wrote the NEJM letter did not speak to the woman herself, according to Science. But after she spoke to officials from the Robert Koch Institute, Germany’s public health agency, and Bavarian officials, she said that she “felt tired, suffered from muscle pain,” and took fever-lowering medication while in Germany.
While Germany’s health agency spokespeople would only confirm that the woman had symptoms, the Robert Koch Institute has submitted a letter to NEJM, presumably to correct the record.
China has claimed to have data showing asymptomatic transmission occurring within the country, but U.S. health officials previously said that they did not have enough data to make that claim. That appeared to change after the publication of the NEJM letter.
Indeed, asymptomatic transmission outside China was alluded to when the U.S. declared a public health emergency for novel coronavirus on Friday. And on Saturday, the World Health Organization (WHO) reported “third-generation” transmission of the virus in Germany.
Science said that WHO officials and European partner agencies have been notified with the new information. As of Tuesday, NEJM has not published a letter of correction.
https://www.medpagetoday.com/infectiousdisease/publichealth/84688

Biogen up 18% on reported favorable patent ruling for Tecfidera

Biogen (BIIB +17.5%) jumps on modestly higher volume in apparent response to or in anticipation of a favorable ruling from the USPTO’s Patent Trial and Appeal Board regarding a challenge to a key patent protecting top selling MS drug Tecfidera (dimethyl fumarate). A decision was expected no later than tomorrow, February 6.

Would-be generic competitor Mylan N.V. (MYL +2.9%) is challenging the validity of the patent, which, if successful, would erase eight years of exclusivity in the U.S.

Tecfidera accounted for ~30% of the company’s sales last year.

https://seekingalpha.com/news/3538715-biogen-up-18-on-reported-favorable-patent-ruling-for-tecfidera

BARDA OKs additional funding for development of Spero antibiotic

The U.S. Biomedical Advanced Research and Development Authority (BARDA) has exercised its option under a 2018 contract to provide an additional $15.9M of funding to Spero Therapeutics (SPRO -2.1%) to support the development of tebipenem HBr for the treatment of complicated urinary tract infections (cUTI), a Fast Track- and Qualified Infectious Disease Product-tagged indication in the U.S.

A Phase 3 study, ADAPT-PO, is ongoing with topline data expected in Q3.

Tebipenem HBr (tebipenem pivoxil hydrobromide; formerly SPR994) is an oral carbapenem antibiotic marketed in Japan by Meiji Seika Pharma Co., Ltd. for infections related to pneumonia, otitis media (ear infection) and sinusitis in children.

https://seekingalpha.com/news/3538623-barda-oks-additional-funding-for-development-of-spero-antibiotic

Tesla tumbling after confirming China deliveries delay

Tesla (NASDAQ:TSLA) confirms deliveries scheduled for early February in China will be delayed due to the coronavirus outbreak. Execs expects the production line to catch up once the outbreak gets better and the Shanghai factory is reopened, although that timetable is unclear.

The EV automaker has been relatively immune from broad concerns over a reeling Chinese economy as investors and analysts focus on the long-term picture.

Wedbush is out with a note this morning in that vein. “We are currently modeling ~20K deliveries in the key China region for the March quarter. In our opinion the current situation is more bark than bite as the aggressive trajectory of Giga 3 production and demand out of Shanghai look very strong out of the gates and the potential to hit 150k units/demand out of this region over the next year still remains intact,” forecasts analyst Dan Ives.

https://seekingalpha.com/news/3538550-tesla-tumbling-after-confirming-china-deliveries-delay