Cure for Hepatitis B Pushed

The International Liver Conference kicked off here today with a push to find a cure – not just maintenance treatment – for the one quarter billion people living with hepatitis B virus (HBV) infection, but researchers said that finding a cure could be elusive, and it certainly won’t come quickly.

“I think we are still at least 3 years away from starting a Phase III clinical trial that would probably include a combination therapy,” said Massimo Levrero, PhD, a member of the governing body of the International Coalition to Eliminate HBV (ICE-HBV) and director of the Cancer Research Centre of Lyon in France.

Levrero, one of several participants in a press conference at the start of the 5-day annual meeting of the European Association for the Study of the Liver, told MedPage Today that there are numerous drug treatment candidates being tested to attack various structures of the virus, but he compared HBV to HIV rather than hepatitis C virus – for which an 8-week functional cure is now available.

“Hepatitis B is very different than hepatitis C, and it is very difficult to eradicate, as is HIV,” he said.

While HIV eradication is very rare – with only two known and verified cures worldwide, hepatitis B has been cured by various methods – but in less than 10% of cases, said Peter Revill, PhD, senior medical scientist at the Victorian Infectious Diseases Reference Laboratory in Melbourne, Australia. At the press conference, Revill suggested that as many as one million people in the world have been cured of hepatitis B – but there are an estimated 257 million people living with hepatitis B infection.

Revill said that more than 887,000 deaths are caused by the virus every year. Chronic HBV causes almost 40% of cases of hepatocellular carcinoma, which is the second leading cause of cancer-related mortality worldwide. The most affected areas of the world for hepatitis B infection are Africa and Asia, but the disease is found throughout the world.

He noted that antivirals can suppress the virus but do not affect the risk of causing liver cancer. Levrero said that when people have to take drugs for long periods of time – sometimes decades in the case of HBV treatment – there is a waning of compliance, which makes the need for a cure more imperative.

The ICE-HBV initiative was the subject of a think tank discussion as well as the press briefing; the conference was expected to attract 8,000 physicians, researchers, scientists, and allied healthcare professionals. Along with its presentation, the strategy was published simultaneously online in The Lancet Gastroenterology & Hepatology.

‘Global Public Health Challenge’

“Chronic HBV infection is a global public health challenge on the same scale as tuberculosis, HIV, and malaria,” Revill and colleagues said. “ICE-HBV is a coalition of experts dedicated to accelerating the discovery of a cure for chronic hepatitis B. Following extensive consultation with more than 50 scientists from across the globe, as well as key stakeholders including people affected by HBV, we have identified gaps in our current knowledge and new strategies and tools that are required to achieve HBV cure.”

“We believe that research must focus on the discovery of interventional strategies that will permanently reduce the number of productively infected cells or permanently silence the covalently closed circular DNA in those cells, and that will stimulate HBV-specific host immune responses which mimic spontaneous resolution of HBV infection,” the team continued. “There is also a pressing need for the establishment of repositories of standardized HBV reagents and protocols that can be accessed by all HBV researchers throughout the world.”

Revill noted that although vaccination against HBV is effective, vaccination cannot eradicate the disease in people who are already infected: “Once chronic infection is established, patients are exposed to significant risk of liver disease including chronic hepatitis, cirrhosis, and hepatocellular carcinoma,” he said. “The natural history of chronic HBV infection usually consists of up to five stages, which differ in the level of viral replication, viral antigen expression, and inflammatory activity in the liver.”

The investigators concluded: “The time for development and implementation of a safe, affordable, widely available cure for chronic hepatitis B virus infection is now. HBV research funding has for too long been woefully inadequate; this must be addressed. ICE-HBV seeks to achieve its goals by fostering collaborative partnerships with researchers (both within the HBV field and outside), clinicians, the pharmaceutical industry, and a range of stakeholders, including communities affected by chronic hepatitis B; we invite these groups to join forces with ICE-HBV in a global effort to discover, develop, test, and implement HBV cure strategies, to help ensure that the WHO goal of HBV elimination as a public health threat by 2030 is achieved.”

The research was supported by the Australian Academy of Science, France Recherche (ANRS), and the Peter Doherty Institute for Infection and Immunity, and supported in part by the intramural research program of the National Institute of Diabetes and Digestive and Kidney Diseases.

Revill disclosed relevant relationships with Gilead Sciences; Levrero reported relevant relationships with Bristol-Myers Squibb, ContraVir, Galapagos, Arbutus, Gilead, Janssen, Roche, and MSD.

• Primary Source

  The Lancet Gastroenterology & Hepatology

  Source Reference: Revill P, et al “A global scientific strategy to cure hepatitis B” Lancet Gastroenterol Hepatol 2019; DOI: 10.1016/S2468-1253(19)30119-0.

https://www.medpagetoday.com/meetingcoverage/easl/79131

Wockhardt gets US FDA OK for blood cancer generic

Pharmaceutical and biotechnology major Wockhardt has received approval from the United States Food & Drug Administration (US FDA) for an ANDA for 50mg injection of Decitabine, which is used to treat certain forms of cancer.

Wockhardt’s Decitabine Injection is a generic version of Dacogen, marketed in USA and other countries by Otsuka.

Decitabine is used to treat Myelodysplastic syndromes (MDS), a group of cancers in which immature blood cells in the bone marrow do not mature and therefore do not become healthy blood cells. According to IQVIA February 2019 data, the product has sales of $120 million in the US.

‘This is the third US FDA approval for an oncology product for Wockhardt during the past three months, and has added to our growing portfolio of cancer drugs’ said Dr. Habil Khorakiwala, Founder Chairman, Wockhardt Group. ‘Wockhardt has been sustaining growth in the US and worldwide through an increasing portfolio of specialty products including oncology drugs’ he said.

Wockhardt will be launching this product in the United States, in a short period of time. With its nationwide distribution network and its excellent relationship with all major trade, retail and institutional customers, Wockhardt is already a significant player in the US pharmaceutical market.

The product is being manufactured at a contract manufacturing facility, based near Hyderabad, India.

https://www.marketscreener.com/WOCKHARDT-LIMITED-9059063/news/WOCKHARDT-RECEIVES-US-FDA-APPROVAL-FOR-CANCER-DRUG-10TH-APRIL-2019-28390962/

French court finds Bayer’s Monsanto liable for farmer’s sickness

A French court has ruled that Monsanto was liable for the sickness of a farmer who inhaled one of its weedkillers, in another legal setback for the Bayer-owned business over health claims.

In the latest stage of a decade-long legal tussle, the appeals court in Lyon on Thursday found in favour of farmer Paul Francois’ claim that Monsanto’s Lasso weedkiller had made him sick and that the product’s labelling had been inadequate.

Francois, 55, says he suffered neurological problems, including memory loss, fainting and headaches, after accidentally inhaling Lasso in 2004 while working on his farm.

“Mr Francois justifiably concludes that the product, due to its inadequate labelling that did not respect applicable regulations, did not offer the level of safety he could legitimately expect,” the court said in its ruling.

The latest verdict, however, did not determine compensation for the farmer, which will now be considered by another court in Lyon.

Francois is seeking about 1 million euros (862,034.70 pounds) in damages.

Bayer, which acquired Monsanto in a $63 billion deal last year, said it was considering its legal options, including an appeal before France’s highest court.

The German chemicals group added that crop-protection products “do not pose a risk for human health if they are used according to the terms of use set out in their regulatory approval”.

Mr Francois had won rulings against Monsanto in 2012 and 2015 before France’s top court overturned the decisions and ordered the new hearing in Lyon.

“We are all happy to have won but it came at a heavy price,” Francois told reporters in Paris.

“It’s a big sigh of relief. It’s been 12 years of fighting, 12 years during which I had to put my whole life on hold.”

Lasso was banned in France in 2007 after the product had been withdrawn in some other countries.

It used a different active substance to glyphosate, the chemical contained in Monsanto’s best-selling weedkiller Roundup and the target of lawsuits in the United States over alleged cancer links.

The company has been found liable in two trials in California brought by cancer sufferers who have been awarded tens of millions of dollars in damages. Bayer is appealing against those rulings.

The legal troubles surrounding glyphosate have contributed to Bayer losing about 30 billion euros in market value since last August. The group’s chief executive on Thursday said it was “massively affected” by the litigation.

After the announcement of the decision, Bayer’s shares extended a fall to trade about 1.5 percent down before recovering some of the losses.

https://www.marketscreener.com/BAYER-AG-436063/news/Bayer-French-court-finds-Bayer-s-Monsanto-liable-for-farmer-s-sickness-28390235/

Societe Generale corrects error in work, downgrades Alcon to Sell

Societe Generale analyst Le Louet, who initiated Alcon yesterday with a Buy rating and CHF67 price target, said she identified an error in her model and has downgraded the stock to Sell from Buy after correcting her work. Her corrected discounted cash flow valuation analysis leads her to a new price target of CHF44, said the analyst, who apologized for the error and noted she made no changes to her P&L forecasts.

https://thefly.com/landingPageNews.php?id=2891524

Scynexis in spotlight with a weapon that may fight Candida auris superbug

When Marco Taglietti flew from Amsterdam to Milan earlier this week, a neighboring passenger happened to ask what he did for a living. Upon learning he was an infectious disease specialist, the passenger inquired whether he had come across the recent report about this “difficult-to-treat new fungus.” Upon disembarking, Taglietti slid into his Uber, when his driver professed an interest in his profession. The physician’s answer produced a now-familiar response: Have you heard about Candida Auris?

Such is the state of affairs. A comprehensive report by the New York Times last Saturday put the spotlight on a stubborn, difficult-to-diagnose and treat fungal infection: Candida Auris or C. auris. The largely drug-resistant microbe, which thrives in people with compromised immune systems, has emerged mysteriously across the globe, popping up in Venezuela, Britain, the United States and having taken root in India, Pakistan and South Africa.

Taglietti, who has helped bring 35 drugs to market with stints at Forest Labs, Stiefel Labs and Schering-Plough, runs a small biotech out of Jersey City, New Jersey called Scynexis $SCYX — ostensibly the only US drug developer with an antifungal in late-stage clinical development for the oft’ deadly pathogen.

“The CDC has been actually been talking about it for the last couple of years, making dire predictions…but apparently no-one was listening,” Taglietti said in an interview with Endpoints News.

More than 1 in 3 patients with invasive C. auris infection (for instance, an infection that affects the blood, heart, or brain) die, according to the CDC, which has deemed the pathogen a “serious global health threat.” As of February 28, the US agency has recorded 587 confirmed cases and 30 probable cases this year.

“C. auris attaches from person to person, to things, to clothes, to the walls. This is why the CDC is so concerned about this pathogen, its very sticky, very persistent and tends to spread,” Taglietti said, noting that the publishing of the NYT story inspired a series of reports globally that helped the fungus has permeated the cultural zeitgeist.

“From what we know, we are the only company assessing an investigational treatment in C. auris. I’m sure now, many others will follow.”

It has been decades since a fresh family of antifungals has come on to the market — at the moment there are three classes of antifungals in clinical use, including azoles and echinocandins.

The most popular antifungals in use today were introduced in the 1980s and this class is increasingly losing its potency, as fungal pathogens become more resistant. Scynexis’s lead experimental drug — ibrexafungerp — belongs to a new class of antifungals called glucan synthase inhibitors, and has shown to be effective against a broad range of of fungal infections, including resistant strains, Taglietti said.

Last October, the company initiated a late-stage open-label study called CARES in C. auris patients. In a presentation on Friday, Scynexis will present data at a medical conference on two patients who were successfully treated with the oral ibrexafungerp from the ongoing study, which has enrolled several patients so far.

The passage of the limited population pathway for antibacterial and antifungal drugs (LPAD) pathway — established by the 21st Century Cures Act — allows the FDA to approve certain anti-infective products on the basis of limited clinical data. Scynexis is working with the FDA to sort out how much ibrexafungerp data will make the cut for C. auris, Taglietti said.

The drug is also being tested for other infections. It is in a Phase III study for vaginal yeast infections. Topline data are expected in the first half of 2020, and if positive, the company expects to file a marketing application in the latter half of the year.

One of the biggest challenges facing the field of antifungal drug development is the lack of incentives, such as those afforded to companies in the antibacterial and antiviral space, Taglietti said.

When the company approached BARDA for funding, they were told antifungals were not a priority in Washington, he said. “I hope this awareness will now reach Washington.”

As superbugs flourish, the industry players contributing to the arsenal of antimicrobials are dwindling. Companies in the antibiotic space have their own set of troubles.

Drugmakers are enticed by greener pastures, compared to the long arduous path to antibiotic approval that offers little financial gain as treatments must be priced cheaply, and often lose potency over time as bacteria grow resistant. Beyond the incentives already in place to push drugmakers to develop antibiotics, there have been calls to bring on “pull incentives,” or policy measures to increase the value of a marketed antibiotic by rewarding drugmakers only after their antibiotic is approved by the FDA.

Taglietti does not see antifungals facing a similar hurdle. “There is a (bigger) need for antifungals, therefore they will not go the same way antibacterial sales have gone. The last antifungal approved in 2015 is making $150 million in its third year of sales…more than the last 4 or 5 antibacterials combined.”

Scynexis finds itself in the spotlight with a weapon that may fight a superbug that’s scaring the world to death

Viking Therapeutics data ‘compelling’ at low doses, says H.C. Wainwright

Viking Therapeutics reported additional results this morning from its 12-week Phase 2 data of the lower 5mg dose of VK2809 in patients with non-alcoholic fatty liver disease. The “compelling” results show “impressive” safety and efficacy at low doses, H.C. Wainwright analyst Joseph Pantginis tells investors in a research note. Importantly, VK2809 at low doses is able to “significantly reduce” liver fat content in 12 weeks to an extent similar to the one demonstrated by the higher doses tested, says the analyst. He reiterates a Buy rating on Viking Therapeutics with a $31 price target.
https://thefly.com/landingPageNews.php?id=2891489

Evofem up on bullish $80M capital raise

Thinly traded micro cap Evofem Biosciences (EVFM +13.2%) is up on modestly higher volume, albeit on turnover of only 25K shares, in apparent response to its $80M capital raise that it will use to push birth control gel Amphora over the finish line and prepare for commercial launch.

PDL Biopharma (PDLI) will lead the private round, buying $60M of newly issued EVFM common shares at $4.50, a 20% premium over the current price of $3.75.

EVFM stockholders Woodford Investment Management and Invesco Asset Management have the option to invest up to $10M each at the same price.

https://seekingalpha.com/news/3450009-evofem-13-percent-bullish-80m-capital-raise