Dicerna Doses 1st Volunteer in Phase 1 Trial of Chronic Hep B Treatment

Dicerna Pharmaceuticals, Inc. (NASDAQ: DRNA), (the “Company”) a leading developer of RNA interference (RNAi) therapeutics, today announced the dosing of the first human volunteer in its Phase 1 clinical trial of DCR-HBVS, the Company’s investigational GalXC^TM-based therapy for the treatment of chronic hepatitis B virus (HBV) infection in adults. The Company anticipates human proof-of-concept data from the Phase 1 trial, which is known as DCR-HBVS-101, in the second half of 2019.

“The dosing of the first human in the DCR-HBVS-101 trial brings us a step closer to the potential availability of an innovative therapy for patients with chronic hepatitis B, a serious liver infection that can lead to advanced hepatic disease or liver cancer if not treated effectively,” said Ralf Rosskamp, M.D., chief medical officer of Dicerna. “We are hopeful that this three-part Phase 1 trial will validate RNA interference as a viable clinical strategy against chronic hepatitis B infection, based upon our encouraging preclinical data on DCR-HBVS.”

DCR-HBVS is comprised of a single GalXC molecule that targets HBV messenger RNAs (mRNAs) within the hepatitis B surface antigen (HBsAg) gene sequence region. Preclinical studies with a standard mouse model of HBV infection showed DCR-HBVS led to greater than 99% reduction in circulating HBsAg, suggesting superior HBsAg suppression (both in magnitude and duration of suppression), compared to targeting within the X gene sequence region.

“RNAi-based therapy has the potential to change the treatment paradigm for patients with chronic HBV infection. By silencing not only the S antigen but also other viral genes, through a powerful and long-acting mechanism, RNAi-based therapy could tip the balance toward allowing the patient’s own immune system to mount an effective immune response. This approach could help eradicate HBV and remove the need for life-long therapy,” said principal investigator Edward Gane, MBCHB, M.D., deputy director and hepatologist of the New Zealand Liver Transplant Unit at Auckland City Hospital and clinical professor of Medicine at the University of Auckland School of Medicine. “Given the encouraging inhibitory activity of DCR-HBVS in animal studies, as well as its favorable preclinical safety profile, we eagerly anticipate the first results from healthy volunteers in the DCR-HBVS-101 trial, and then in the second part of the study, from patients with chronic hepatitis B.”

https://www.biospace.com/article/releases/dicerna-announces-dosing-of-first-volunteer-in-phase-1-clinical-trial-of-dcr-hbvs-designed-for-the-treatment-of-chronic-hepatitis-b-virus/

Advaxis to Present New Data at Immuno-Oncology 360° Conference

 Advaxis, Inc. (NASDAQ:ADXS), a late-stage biotechnology company focused on the discovery, development and commercialization of immunotherapy products, today announced that an overview of the Company’s proprietary Lm platform and new information regarding the Company’s neoantigen-directed therapy programs, ADXS-NEO (customized, personalized neoantigens) and ADXS-HOT (off-the-shelf, hotspot or shared neoantigens and other antigens), will be presented during a plenary session at the Immuno-Oncology 360° conference on February 6, 2019. The conference is being held at the Crowne Plaza Times Square in New York City; the plenary session begins at 4:00 p.m. ET and the Advaxis presentation is scheduled to begin at 4:40 p.m. ET.

The presentation will be made by Andres A. Gutierrez, M.D., Ph.D., Chief Medical Officer and Executive Vice President of Advaxis, and Robert G. Petit, Ph.D., Chief Scientific Officer and Executive Vice President of Advaxis. Advaxis intends to issue a news release on February 6, 2019, that summarizes the presentation by Drs. Gutierrez and Petit.

ADXS-NEO, the Company’s personalized neoantigen program, is in an ongoing Phase 1 dose-escalation study to treat a variety of cancers. ADXS-HOT is the Company’s off-the-shelf program and consists of several different drug constructs which target hotspot or shared neoantigens, and other antigens. The first drug construct from this program is ADXS-503, or HOT-Lung, for the treatment of non-small cell lung cancer. ADXS-503 is expected to enter the clinic this quarter.

https://www.biospace.com/article/releases/advaxis-to-present-an-overview-of-its-lm-platform-and-new-information-on-its-neoantigen-directed-therapy-programs-at-the-immuno-oncology-360-conference/

Record US Opioid Mortality Level Likely to Remain for Years: U.S. News

Opioid mortality is five times higher than it was at the turn of the century and is likely to remain at the same level or rise even higher for years to come, according to an exclusive analysis for U.S. News & World Report.

The examination of nearly two decades of drug overdose deaths, using data from the Centers for Disease Control and Prevention, indicates short-term changes in the death toll – figures commonly looked to for signs of progress – mask the true magnitude of the opioid epidemic and the damage done in America.

Key findings from the analysis and related reporting include:

• After years of steady increases, opioid mortality rates have soared to a level that likely marks the country’s “new normal.” The stabilization at this high rate – 14.9 deaths per 100,000 population in 2017 – indicates the idea that the country is beginning to turn the tide on the opioid crisis is premature.
• The biggest recent increases in mortality have emerged among black Americans. Between 2005 and 2013, the rate of fatal opioid overdoses among blacks in America averaged 3.7 deaths per 100,000 population, far below the 7.6 average rate for whites during that time. Yet between 2014 and 2017, the fatal overdose rate among blacks rose by 130 percent, compared with a 61.5 percent increase for whites over that period.
• On average, higher rates of deaths of despair cut into a community’s average life expectancy more than high violent crime rates or low rates of health insurance coverage.
• A look at state death rates underscores how some opioid data can paint a misleading picture about the crisis as a whole. Opioid deaths in West Virginia in 2017 occurred at an age-adjusted rate of 49.6 per 100,000 people, while in the same year, Ohio’s opioid death rate was 39.2 per 100,000. However, Ohio saw 4,293 opioid overdose deaths that year, compared with West Virginia’s 833.
• CDC data suggest Texas has a relatively small number of opioid deaths for a state of its size, but the data are incomplete. With a population of roughly 28 million, Texas reported only 1,458 opioid deaths in 2017, with a mortality rate of 5.1 per 100,000 population. However, the state’s current system to record and track these deaths is likely to downplay the magnitude of the problem, local researchers say.

“Too often, public health officials, journalists and politicians from both parties have been chasing the next data point in the opioid crisis and have claimed that we’re successfully tackling the crisis, but through these findings we see that the opioid crisis is getting worse, not better,” said Rocco Perla, who led the U.S. News analysis and is co-founder of a new nonprofit, The Health Initiative. “Only when we look at the data over time can we learn what is or isn’t working and which of the opioid-focused dollars, task forces and agencies are actually saving lives.”

These findings are accompanied by in-depth articles that spotlight the toll the opioid epidemic has taken on varied communities across the country including:

• The Three Distinct Stages of the Opioid Crisis: An analysis of how the opioid epidemic has unfolded in three distinct waves over the last two decades.
• How We Treat Youth Addiction: Is there a treatment gap between adults and children suffering from opioid dependence?
• The Opioid Crisis and the African-American Community: A look at the opioid epidemic’s effect on Chicago.
• How the Epidemic Shifted Family Dynamics and Strained Community Resources: A spotlight on Dayton and Montgomery County, Ohio.
• The New First Responders: A photo essay documenting the ordinary citizens now armed with overdose-reversal drugs.

“Through in-depth analysis and quality journalism, we are able to examine health disparities affecting populations across the country,” said Brian Kelly, editor and chief content officer of U.S. News. “Our reporting shines a light on the substantial toll communities have paid as a result of the rising opioid epidemic. We hope these findings can initiate change in areas across the nation that are deeply struggling.”

https://www.biospace.com/article/releases/record-opioid-mortality-in-america-likely-to-remain-at-current-lethal-level-for-years-u-s-news-analysis-finds/

Pfizer’s Cancer Portfolio Expected to Rake in $8.3 Billion in 2019

Pfizer is a big company with a diverse portfolio, but it hasn’t really been noted for its presencein the oncology market. The majority of its successful drugs are in primary care and heart medicine, like Lipitor (atorvastatin) for cholesterol, Lyrica (pregabalin) for neuropathic pain and fibromyalgia, Zithromax (azithromycin), an antibiotic, and Viagra (sildenafil) for erectile dysfunction.

But now, Pfizer offers 17 drugs to treat cancer, with four approved in the U.S. in 2017. The oncology portfolio, according to EvaluatePharma, is projected to bring in $8.3 billion in sales in 2019. For the first time, cancer drugs are expected to sell more than the cardiac and primary-care medicines.

“At Pfizer, oncology is one of the core components of the organization—going from an almost afterthought,” Andy Schmeltz, global president of Pfizer Oncology, told the Wall Street Journal.

WSJ indicates that marketing executives in the biopharma industry like oncology because promoting these drugs to oncologists and hospitals takes a smaller sales force than to market cholesterol and hypertension drugs to primary care physicians. And according to EvaluatePharma, oncology drug sales are projected to hit $138 billion globally this year with an 11-percent growth rate in 2019. They’re fairly pricey drugs as well, with a typical cancer drug having a list price of $100,000.

Emma Walmsley, chief executive officer of GlaxoSmithKline, told WSJ, “The unmet need as well as the biological advances are still so significant that there’s a lot of room for a lot of people to be successful.”

And, of course, 2019 marked the acquisition of cancer specialist Celgene by Bristol-Myers Squibb for a whopping $74 billion. That combined company will have nine products with more than $1 billion in annual sales each. Its oncology pipeline for solid and hematologic tumors will be led by Opdivo, Revlimid, Pomalyst and Yervoy.

For years, there were four so-called “pillars” of oncology treatment. They were surgery, radiotherapy, chemotherapy, and targeted therapies, which recognize specific features on cancer cells. But over the last five years or so, a fifth pillar has been added, immuno-therapy or immuno-oncology. This includes PD-1 checkpoint inhibitors like Opdivo and Merck’s Keytruda, CTLA-4 checkpoint inhibitors like Yervoy, and others. It also includes CAR-T therapies like Novartis’ Kymriah (tisagenlecleucel) and Gilead/Kite’s Yescarta (axicabtagene ciloleucel).

The immuno-oncology global market alone is expected to pass $100 billion by 2022.

Pfizer began building its oncology capacity in 2008, partly to offset an oncoming patent cliff for some of its biggest non-cancer drugs. This led to the company hiring researchers like Mace Rothenberg, then with Vanderbilt University Medical Center and now the company’s chief medical officer.

Pfizer’s oncology focus is on breast, prostate and lung cancer. Its first cancer drug, Sutent, to be approved since 1970 received the thumbs-up in 2006. In 2011, the FDA approved its lung cancer drug Xalkori. Its top-selling cancer drug is Ibrance, which brought in almost $3 billion in the first nine months of 2018. Three of Pfizer’s 17 oncology drugs are biosimilars, which are essentially generic versions of biologics drugs.

Despite these successes, Pfizer has struggled in the new immuno-oncology arena. Its primary drug in this category is Bavencio, developed with Darmstadt, Germany’s Merck KGaA and approved in 2018 for two rare cancers, metastatic Merkel cell carcinoma (mMCC) and locally advanced or metastatic urothelial carcinoma (UC). It has failed in four late-stage trials for other cancers, however. Part of Pfizer’s strategy—like most companies in the oncology space—is to focus on combination therapies that use multiple drugs.

https://www.biospace.com/article/pfizer-s-cancer-portfolio-expected-to-rake-in-8-3-billion-in-2019/

Piper a buyer of Alexion on weakness, says Ultomiris data ‘look good’

After Alexion released top-line results for a Phase 3 trial of Ultomiris in complement inhibitor-naive aHUS patients, Piper Jaffray analyst Christopher Raymond said he believes the data “look good,” stating that a comparison to Soliris is not “apples-to-apples” since management tells him that patients in the Ultomiris study were sicker than Soliris’ Phase 3 patients with less favorable metrics across several measures. No new safety signals were observed and although four patient deaths were reported, none were attributed to Ultomiris, Raymond added. The analyst, who would be a buyer of shares on the weakness, keeps an Overweight rating and $180 price target on Alexion.
https://thefly.com/landingPageNews.php?id=2854531

Novozymes upgraded to Neutral from Sell at Goldman Sachs

Goldman Sachs analyst Fulvio Cazzol upgraded Novozymes to Neutral while lowering his price target for the shares to DKK 279 from DKK 300. The analyst believes the company’s risk/reward is more balanced following its 2019 organic growth guidance of 3%-6%. He says expectations have been rebased.

https://thefly.com/landingPageNews.php?id=2854145

Piper ‘strongly’ recommends buying Neuronetics after 22% selloff

Shares of Neuronetics have fallen 22% this year amid concerns over the impact of competition on its financial outlook along with a delay in Japan, Piper Jaffray analyst Matt O’Brien tells investors in a research note. The analyst says he “dug in on” the competitive systems and does not believe they carry the “feature-rich characteristics” of Neuronetics’ NeuroStar product. Further, he had never modeled sales in Japan in 2019 or 2020. As such, O’Brien views the competitive concerns as overdone and “strongly” recommends purchase of Neuronetics shares, which he says is a 20% plus top-line grower trading at less than three times sales.

https://thefly.com/landingPageNews.php?id=2854151