The SEC must be totally blind, or for some reason, not willing to put resources on this problem. Makes you wonder what influence the Short Sellers have over the SEC.
Nucleos(t)ide analogues (NUCs) for chronic hepatitis B treatment achieve high rates of viral suppression and are generally well tolerated. Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are the currently preferred first-line agents. The safety of these agents in clinical practice is particularly relevant since long-term treatment is usually required.
To summarise and critically discuss recent real-world evidence on the safety of treatment with ETV or TDF in hepatitis B virus (HBV)-monoinfected patients.
PubMed and conference proceedings up to 15th June 2015 were searched using the terms ((((Hepatitis_B) OR HBV) AND ((tenofovir) OR entecavir)) AND (((lactic_acidosis) OR bone) OR renal)).
In selected populations included in registration studies, both ETV and TDF were well tolerated with no clinically significant renal toxicity or lactic acidosis. Growing ‘real-world’ clinical experience with these agents includes some reports of ETV-associated lactic acidosis and TDF-associated renal impairment; however, evidence from cohort studies appears to be conflicting. In the case of ETV-related lactic acidosis, a small number of cases have been reported, all in patients with decompensated cirrhosis. The degree of association between TDF treatment and changes in markers of renal function varies between studies: discrepancies may result from the use of different definitions and cut-offs for reporting renal toxicities, and differences in patient populations.
Pre-treatment and on-treatment monitoring of eGFR and phosphorus, with prompt appropriate dose adjustment or treatment switch can minimise the impact of NUC renal toxicity. Standardisation of measures of renal impairment and identification of early molecular markers remain an unmet need.
Thanks for the update, was wondering if the securities dismissal is final yet. Very unlikely Marshall will change her mind, IMO.
One point to note is how smart ARWR management is to be conducting major trials in China where the problem is great.
An estimated 248 million individuals worldwide are chronically infected with the hepatitis B virus (HBV) . Approximately 40 % live in China, where an estimated 100 million people are chronically infected, and where up to 500,000 people die annually from HBV-related complications, including primary liver cancer (hepatocellular carcinoma [HCC]) [2-5]. In China, most infection occurs at birth (perinatal transmission) or during early childhood, leading to high rates of chronic infection [4, 5]. The high prevalence of chronic HBV infection in China has yielded a high burden of HBV-related HCC incidence and mortality, with 55 % of liver cancer deaths worldwide occurring in China . HBV immunization programs administered by the Chinese Ministry of Health and the World Health Organization (WHO), including the universal vaccination of newborns program begun in 1992, have improved HBV vaccine coverage in parts of China, which is reflected in a recent decline of prevalence rates [7, 8]. However, HBV vaccination does not help those who are already infected, and chronic HBV infection is still a considerable health issue in China with a serious public health impact.
The key to reducing morbidity and mortality associated with chronic HBV infection is improving rates of HBV screening and ensuring that infected individuals receive appropriate medical management [9, 10]. This is especially needed in areas that have high HBV prevalence and HCC incidence. However, multiple barriers result in low levels of screening, diagnosis, care and treatment for HBV. Key barriers to screening and vaccination include geography (i.e. rural areas), limited knowledge among the general population and health care providers, and HBV-related stigma Treatment uptake is also low, primarily due to under-diagnosis and cost of antiviral treatment .
If sAG KD is accepted by regulatory authorities as is a surrogate end point, it could mean that ARWR's ARC-520 is going to be approved for its effect on sAG, and never mind seroclearance of sAG or FCs!!!
This is potential for fast track approval and further it would mean use in therapy that could be very profitable.
“Our results confirm that [quantitative hepatitis B surface antigen level (qHBsAg)] off-therapy can predict durability of [chronic hepatitis B (CHB)] patients stopping entecavir treatment,” Chia-Chi Wang, MD, of the department of gastroenterology at the School of Medicine of Tzu Chi University in Taiwan, and colleagues wrote.
New clinical markers to better predict off-therapy of Baraclude (entecavir, Bristol-Myers Squibb) treatment are necessary, the researchers wrote. Because it shares a complementary relationship with HBV DNA in clinical practice, serum qHBsAg levels were hypothesized by the researchers as a potential clinical marker.
The researchers conducted a multicenter study of 93 patients with chronic HBV without cirrhosis who discontinued entecavir treatment in Taiwan. The primary endpoints were clinical relapse and SVR, which they defined as undetectable serum HBV DNA levels at 12 months off-therapy.
All 12 patients who did not achieve therapeutic end points experienced clinical relapse. In the 81 patients who achieved the end points, 54.3% experienced clinical relapse and 13.6% experienced SVR. The researchers found that serum HBV DNA at 3 months and 6 months off-therapy were associated with clinical relapse over time, whereas qHBsAg level at 6 months off-therapy had a marginal effect. In addition, they found that end-of-treatment qHBsAg levels were associated with SVR (P = .009).
Serum qHBsAg level less than 100 IU/mL is recognized as a new therapeutic end point, the researchers wrote.
“[This] can serve as a surrogate end point of existing treatment guidelines,” they wrote.
For ARWR holders, this seems to be a major development as a surrogate end point would be a major lift towards regulatory approval for a drug that blocks sAG.
Exelixis Announces Results from Randomized Phase 2 Trial CABOSUN Demonstrate Cabozantinib Significantly Improved Progression-Free Survival versus Sunitinib in Previously Untreated Advanced Renal Cell Carcinoma
– Exelixis to consult with regulatory authorities to determine next steps in development and submission strategy for cabozantinib in first-line renal cell carcinoma –
Helpful to see the state of advances in fighting Advanced Renal Cell Carcinoma and the potential for ARWR to have an impact in the needs here.
The authorities in China have agreed swingeing price cuts for three drugs in a bid to curb escalating healthcare costs.
The reductions affect GlaxoSmithKline's hepatitis B and HIV therapy Viread (tenofovir), AstraZeneca's lung cancer drug Iressa (gefitinib) and Conmana (icotinib) - another lung cancer treatment made by Chinese firm Betta Pharmaceuticals.
Viread's price has been reduced by more than two thirds to 490 yuan ($75) per month from 1,500 yuan, while EGFR inhibitor Iressa will see its price cut from 15,000 to 7,000 yuan. Conmana - another EGFR inhibitor - sees its price reduced from 12,000 to 5,500 yuan.
The price reductions are a blow to companies hoping to expand in emerging markets such as China, with prospects already dented by the downturn in the global economy, pricing pressure on off-patent drugs and long and uncertain product approval times caused by ongoing regulatory reforms.
Both GSK and AZ have previously suggested that emerging markets are platforms for revenue growth. Now, with China's attention turning to the price of in-patent drugs as well as generics, there are concerns the entire pharma sector in the world's second-largest economy may be affected.
Maybe, but ARWR does not focus on that right now. ARC-HIF2 is designed to inhibit the production of HIF-2α, which has been linked to tumor progression and metastasis in ccRCC. Arrowhead believes it is an attractive target for intervention because over 90% of ccRCC tumors express a mutant form of the Von Hippel-Landau protein that is unable to degrade HIF-2α, leading to its accumulation during tumor hypoxia and promoting tumor growth.
n a sweeping blow to Wall Street investment giants, the U.S. Supreme Court today unanimously allowed lawsuits against "naked" short sellers in state courts to proceed.
The high court ruled unanimously that shareholders are not confined to federal court when seeking recourse for securities violations. Granting “due deference to the important role of state courts,” the Court reinforced federalist principles while clarifying congressional intentions to limit the federal government’s role.
The ruling, which could give a new boost to startups and small companies targeted by short sellers, showed a rare moment of ideological agreement in the court. Justice Elena Kagan authored the Court’s opinion, and Justice Clarence Thomas, joined by Justice Sonia Sotomayor, issued a concurrence.
In 2012, businessman Greg Manning sued Merrill Lynch and other financial institutions in New Jersey state court for purposefully devaluing his company through systematic “naked” short-selling — a term used to describe selling a stock a seller does not own and has not borrowed. In standard short sales, traders either borrow a stock or make sure that it can be borrowed prior to selling it short in the hope that its value will fall before the transaction must be covered.
The practice has come under increasing scrutiny and has been banned in Germany and other major economies.
Manning, the CEO of the memorabilia company Escala Group, Inc., owned two million shares of the company, which formerly traded on the NASDAQ and is now known as Spectrum Group International, Inc.
I never trust anyone that asks you to "trust me" lol. But I am expecting Arezza to sell very well with the new crew, and this prediction is not that far off my own thinking.
I have the simple 50 day MA at $5.34 and the simple 200 day MA at $5.30, which gives us a $.04 cent cross over today on the day chart at this writing.
The one thing that is sorely lacking is the required volume. When we start seeing the PPS rise on 5 M volume days, I will be much happier with the action. For now I see that ARWR is just following the IBB higher and trending with the IBB leaders. Today, the IBB has climbed above its R1 which is at $266.38 with the IBB being under its R2 which is at $268.57, which ARWR is acting the same, in that it has moved between its R1 and R2 on light volume.
I do think a break above $6.50 will probably attract some buying and the volume might pick up, so hoping we can get the PPS into some kind of up trend and break above this almost 2 year base.
That article was about turning on the immune system, not turning off the cancer.That is an interesting article, but it has little to do with HIF2a which stops tumor growth by withdrawing a growth factor from the cancer gene pool and shutting off the cancer. ARWRs approach is novel and unrecognized in the media, at present.
Good follow through today suggests ARWR will make a run at the recent $6.50 zone high. The technical question will be does it break above $6.50 and keep going?
Notice that we have a confirmed cross of the 50 day MA over the 200 day MA for a clear golden cross with the PPS pulling the averages higher.
The 200 day MA still has a downward slope, so it is worth watching if the move can bend the 200 MA into an upward slope. I think that is likely as ARWR has had quite a long period of undervaluation during which it was held down to the 2014 lows as the data and clinical programs progressed without missing a beat. In technical terms, the stock developed a solid base of support in the $5.00 to $7.00 range and it is "ready" for some news that droves it to a new level. Will that happen?
If the bio sector recovers, it will recover with that sector move. If ARWR can produce some company specific news, such as a report showing seroconversions being obtained, this should have an impact proportionate to the value of the news as an added vector force.
I am just guessing, as usual, but when you think about the move to the new space, the progress with CPs and the indications that ARC-520 is showing immune reactivation signs, how can this not improve on the IFN combination profile of FCs? Soon we find out if the monotherapy works on the early stage disease.
Look at that crazy powerful pipeline that is preclinical which is totally not even valued at anything.
ARWR is moving into the catbird seat. The markets generally have been looking to break to new highs for 1 year. If the broad markets explode upward, with the bios leading the charge, the ARWR potential is off the charts, IMO.
This will drive all undervalued bios back into favor and the Tutes will be buying. ARWR will gain substantially as the bio sector "bounces". Looking for PPS appreciation that will give ARWR some funding choices. The deal, verus the secondary at higher prices. Once ARWR gets over $20, they will be in a great bargaining position and will be able to drive the best bargain. Looking for ARWR to release data that will drive PPS and set up the funding opportunity.