News for heart failure drug LCZ696 part2

Designed to be taken twice a day by a massive group of patients suffering from chronic heart failure, the treatment is a dual-acting angiotensin receptor-neprilysin inhibitor, taking a one-two punch with valsartan and AHU-377. AHU-377 blocks a mechanism of action that threatens two peptides responsible for lowering blood pressure while valsartan improves vasodilation, spurring the body to excrete sodium and water. 


LCZ696 has been living up to its rep as the next big thing in Novartis’s cardiovascular pipeline–a big factor in getting over the profound disappointment caused by the failure of serelaxin with regulators. The clinical work for this drug is being divided into two basic segments. This first part covered at the AHA involves prompting the heart to contract and empty more normally for heart failure patients. The next step, to be covered in an upcoming trial, will examine its ability to complete another essential task for the heart muscle: relaxation and filling.

An initial approval for this drug would open up a huge and growing market in the heart failure field. But further success has the potential to make this drug a player in the lives of 75% to 80% of the entire patient population, says the investigator, one reason why Novartis execs are estimating peak sales at $5 billion or more. Investigators had to compare their new drug with a standard of care for patients. But by extrapolating data from enalapril, they found a “really impressive 32%-34% reduction in cardio mortality and a 45%-50% reduction in hospitalizations.”

News for heart failure drug LCZ696 part1

Joe Jimenez, Novartis CEO  have already expressed just how delighted they are in the Phase III efficacy data that’s been emerging about the heart failure drug LCZ696. Investigators have already noted a 20% reduction in the risk of dying–the key measure behind a full slate of upbeat peak sales estimates. The pharma giant’s biggest challenge now is living up to some heady expectations. And today we learned that there was also a 30% drop in ER visits, a 16% overall slide in hospitalizations as well as a significant reduction in the need for intense therapy at home when compared to patients taking the ACE inhibitor enalapril.


When hospitalized, Novartis reported, LCZ696 and enalapril patients remained under care for approximately the same time, but those on LCZ696 had 18% fewer stays in intensive care and were 31% less likely to need IV drugs to help their heart pump. Patients’ reports of how well they felt and doctors’ assessments of disease severity were also significantly better with LCZ696 than enalapril.

Novartis needs all the upbeat pharmacoeconomic data that it can get on this drug. The company has to put significant clinical distance between its new treatment and the cheap generic enalapril. Analysts estimate that Novartis could charge $7 a day for LCZ696–more than many people’s copay for a month’s worth of generics.

Merck’s hepatitis C cocktail drug fails

After sendin for its hepatitis C regimen, Merck investigators hailed the clear success of an 8-week test but confirmed analysts’ fears in a batch of 4-week data released at the meeting of the American Association for the Study of Liver Diseases.


A mix of grazoprevir/elbasvir (MK-5172/MK-8g out signals that it might be running into trouble with a short-duration study of a new triple combination drug742, MK-5172A)–the company’s investigational NS3/4A protease inhibitor and NS5A inhibitor, in combination with Gilead’s Sovaldi (sofosbuvir), an NS5B nuc inhibitor, clearly hit the mark with a 94.7% cure rate for treatment naïve cirrhotic patients at 8 weeks. But the combination fell well short of the goal line on efficacy at 4 weeks, with a cure rate of 38.7%. At 6 weeks the triple hit an 80% cure rate in the treatment-naïve group of cirrhotic patients while the non-cirrhotic cohort hit 86.7%–shy of the 90% level some analysts believe Merck is likely to face as a competitive hurdle cleared by rivals. All the patients in the study were genotype 1.

Merck’s team declared the numbers were a win, but several analysts concluded that Gilead  is the real winner today. In premarket trading Monday, Gilead’s shares jumped more than 2% as the market potential for Merck’s rival approach faded somewhat. The focus at Merck, which saw its shares slip about 2% this morning, will now be on new studies that include a new hep C drug–MK-3682–recently added to its portfolio.

Merck’s next step will be to cut loose from Sovaldi and get its own MK-3682–acquired in the $3.85 billion Idenix buyout–into a slate of Phase II studies that will look at 8-week results. And Merck says it may once again go even shorter than that. At this point, a variety of new therapies are coming along that will likely eliminate the virus–the rivalry now centers on just how fast it can be done reliably.

Asthma trial prompts Regeneron, dupilumab into PhIII

Dupilumab emerged from Regeneron’s development platform, which has also produced a closely-watched PCSK9 cholesterol drug that is also partnered with Sanofi. While the pharma giant has struggled to develop new drugs–recently bidding its CEO Chris Viehbacher goodbye after an internal squabble with the board–its partnership with Regeneron has produced most of its most promising late-stage drugs.


A win here would be big for Regeneron and huge for Sanofi. Leerink Swann analyst Joseph Schwartz has projected peak annual sales potential for dupilumab at $2.8 billion for two indications–asthma and atopic dermatitis indication. And the partners could be setting the stage for even more.

Regeneron and Sanofi face some competition which is even further advanced in the clinic. Just days ago GlaxoSmithKline  filed for an approval of its IL-5 asthma drug mepolizumab, with Teva (reslizumab) and AstraZeneca (benralizumab) trailing along the IL-5 pathway. AstraZeneca has posted a peak sales estimate for its drug–which has had mixed results in mid-stage trials–at $2 billion. And they all expect that their drugs can also hit the mark for COPD.

Lung cancer diagnosed before it is detected by imaging

Lung cancer is one of the most lethal cancers. According to the American Cancer Society (ACS). Only 15% of these cancers are presently diagnosed at a stage where the disease is localised. COPD is the 3rd leading cause of deaths in the USA, and is mainly caused by smoking.


Studies carried out in animals have clearly shown that invasive tumours shed cancer cells into the bloodstream from the very earliest stages of their formation, even before the tumours are detectable by diagnostic imaging. The possibility of identifying these “sentinel” cells is considered a major asset in the race against time for the early detection, and hence treatment, of cancer. Circulating cancer cells are extremely rare in the bloodstream, are very heterogeneous and fragile, and are difficult to isolate without bias or loss.

The team of researchers led by Paul Hofman used a blood test developed during French research, which isolates all types of tumour cells from the bloodstream, without any loss, leaving them intact. The team studied a group of 245 people without cancer, including 168 patients at risk of later developing lung cancer because they had Chronic Obstructive Pulmonary Disease (COPD). Participants systematically underwent the blood test and standard diagnostic imaging tests. Using the blood test, circulating cancer cells were identified in 5 patients (3%), whereas imaging did not show any nodules in the lungs.

In these 5 patients, a nodule became detectable 1-4 years after detection of circulating cancer cells by the blood test. They immediately underwent surgery, and analysis of the nodule confirmed the diagnosis of lung cancer. Monitoring of the patients for a minimum of one year after surgery showed no sign of recurrence in the 5 patients, leading one to hope that the cancer had been eradicated. At the same time, no nodules were detected during monitoring of subjects who did not have circulating cancer cells, and no cancer cells were detected in the bloodstream of “control” subjects without COPD. Detection of these circulating cells via this blood test could play a key role in early surgical intervention, thus making it possible to aim for early eradication of the primary cancer site.

Statin effect with genetic mutations

A research report published in the Journal of Nature Communications, scientists from the Queen’s University in London,  40000 patients by statin treatment with large analysis study identified two new genetic mutations. These two kinds of genetic mutation can affect the body bad cholesterol on statin therapy response.


Statins are widely used in clinic for drugs that reduce bad cholesterol, the bad cholesterol levels were reduced to 55%, which can effectively reduce the risk of heart disease. Different reactions in patients on statins are not the same. Researchers in this study to analyze the clinical data of 6 groups of random and 10 groups of observational studies to find the effect of patients with genetic mutations on statin response, the researchers found 2 common genetic mutation, the genetic mutation can significantly affect the statin treatment  patients body bad cholesterol levels.

Said Professor Mark Caulfield, this study can help us understand the molecular mechanism of genetic mutations affecting the patient response to statin therapy. We found that individual differences in response to statins, 4 related genetic mutations produce effect only accounted for 5%, of which one have identified genetic mutations can enhance the individual reaction on statins, and second mutation can help the liver uptake of statins, reducing drug reaction.

At present, statins are the most effective and safe clinical medication. Although the use of the same target, in different populations of some statins more effectively, this paper demonstrates the mutual influence of gene network may reaction effect of statins on the body.  The future may help scientists choose statin drugs more effective for different patients.

The bat may is critical in the fight against Ebola virus

Scientists study the Commonwealth Scientific and Industrial Research Institute said, the immune system may be the human bat against Ebola virus mystery. The origin of Ebora virus is still to be determined, but most scientists believe that the Africa fruit bat may be one of its origin. The Australian Commonwealth Scientific and Industrial Research Institute (CSIRO)Dr. Michel Beck said, bats, contained a large number of Ebora virus,  they will not therefore appear symptoms of illness. This is because they can start the immune system in the virus before the attack, let the system of extra work to defend against viruses.


Dr. Beck said, the human problem is to the human body, the activated immune system in viral invasion, but then it was too late. The Ebola  infringement has too serious, the immune system has been unable to resist. She said, another problem is, the bat can overload tolerance of its immune system, but humans cannot. Once the immune system to resist the virus and the height of reactor, which bring the human body harm. In fact, the emergence of the Ebola virus in patients with fever, in vivo or in vitro, bleeding and other symptoms are immune system overreaction consequences.

Dr. Beck said, although now know bats can resist the Ebola virus, but how to make the human immune system can bat as continuous height operation but do not bring any side effects is still a long way to go. Scientists now believe that the Ebola virus is transmitted to primates by African fruit bats, and then spread to humans, because many parts of West Africa have lived by hunting primate animals.