Novartis milestones be proud ! Management take a bow !

from 2012:
Avastin and Lucentis are equivalent in treating age-related macular degeneration
http://www.nih.gov/news/health/apr2012/nei-30a.htm

of course, they cry, because they know science and statistics cut both ways. in this case, they're pissed that they've been called out on the marketing deception.



lucentis future. pick one:

1. will have to match the price of avastin.
2. will be retired from the product portfolio.

 

correct well stated

 

Novartis apologizes for not disclosing side-effects of leukemia drugs sooner
TOKYO Thu Jul 31, 2014 4:01pm IST

Credit: Reuters/Arnd Wiegmann
(Reuters) - The Japanese unit of Novartis AG apologized on Thursday for failing to report to authorities in a timely manner side-effects of its leukemia drugs, in the company's latest scandal in the country.

Novartis Pharma KK, the Swiss drugmaker's wholly owned local subsidiary, said Japan's Ministry of Health, Labour and Welfare ordered the company to improve its practices after the company did not report side-effects of its Gleevec and Tasigna leukemia treatments until around April.

The ministry said serious side-effects must be reported within a month of discovery. Media reports said such side-effects had been known between April 2013 and January 2014.

"We deeply regret that we have allowed this situation to arise, and offer our deepest apologies to our patients, their families, medical professionals, as well as the public," the company said in a statement.

"We take it very seriously, that side-effects, which should be extremely important to any pharmaceutical company, were not reported appropriately."

Earlier in July, Tokyo prosecutors said they would charge the unit and a former employee in connection with allegations of data manipulation to promote its best-selling blood pressure drug Diovan.

The prosecutors office in June arrested Nobuo Shiraishi on allegations that he gave false data to researchers whose work was used for advertising.

https://www.youtube.com/watch?v=9u0EL_u4nvw

 

No offers refused....everything must go !!!!!!!!

http://www.lohud.com/story/news/local/westchester/2014/08/04/novartis-assigns-suffern-property-sale-to-cushman-wakefield/13585975/

 

Novartis loses new bid to dismiss U.S. lawsuit over kickbacks
By Jonathan Stempel

NEW YORK Thu Aug 7, 2014 9:53pm EDT

(Reuters) - A Manhattan federal judge on Thursday said the U.S. Department of Justice may pursue most of its lawsuit accusing Novartis AG (NOVN.VX) of civil fraud for allegedly using kickbacks to boost sales of drugs covered by Medicare and Medicaid.

U.S. District Judge Colleen McMahon allowed the government to continue its False Claims Act case against the Swiss drugmaker over claims submitted to Medicare and some state Medicaid programs for Myfortic, used by patients with kidney transplants, and Exjade, for patients who get blood transfusions.

She also dismissed a part of the case covering claims submitted to state Medicaid programs other than New York's prior to March 23, 2010, when the Affordable Care Act, also known as Obamacare, was enacted.

Novartis, which has offices in East Hanover, New Jersey, had objected to what it called the government's "potentially limitless" theory that any claims submitted by pharmacists who got kickbacks were tainted.

It said the government, to pursue its case, instead must show a kickback scheme actually caused pharmacists to sell Myfortic or Exjade.

Julie Masow, a Novartis spokeswoman, did not immediately respond to requests for comment. A spokeswoman for U.S. Attorney Preet Bharara in Manhattan declined to comment.

The government accused Novartis of providing discounts and rebates from 2005 to 2013 to induce at least 20 pharmacies to switch thousands of patients to Myfortic, an immunosuppressant.

It also said that from 2007 to 2012, Novartis offered patient referrals and rebates to BioScrip Inc (BIOS.O) so that pharmacy would recommend refills of Exjade, which is meant to reduce iron levels in patients.

The government alleged that these activities caused Medicare and Medicaid to pay tens of millions of dollars of improper reimbursements, and violated a federal anti-kickback law. Eleven U.S. states are co-plaintiffs. BioScrip settled for $11.7 million in January.

McMahon had on May 29 allowed the case to proceed, but said she wanted to further review the legal issues.

In her decision on Thursday, she said Congress "gave absolutely no indication" that it intended to limit the reach of the False Claims Act where kickbacks were concerned.

"Where a party falsely certifies compliance with the (anti-kickback law) in connection with a claim, the claim is 'false' as a matter of law, and so is not eligible for reimbursement," she wrote.

McMahon gave the government 21 days to again plead claims she dismissed.

The lawsuit stemmed from a whistleblower case by David Kester, a former Novartis respiratory account manager from Raleigh, North Carolina. He is also pursuing separate claims against Novartis and other companies regarding other drugs.

The case is U.S. v. Novartis Pharmaceuticals Corp, U.S. District Court, Southern District of New York, No. 11-08196.

 

The irrational rationale for cancer drug prices, with Novartis' Zykadia as exhibit A
August 14, 2014 | By Tracy Staton

Peter Bach
Why do cancer drugs cost so much? It's a fundamental question. It's a common one, given the debuts of so many $100,000-plus treatments over the past few years.

But it's mostly a rhetorical question, at least in the U.S., where drug prices aren't scrutinized by panels of cost-effectiveness watchdogs. We all know the stock answer--because companies need to recoup their development costs. Whether we believe it is something else, as Peter Bach of the Center for Health Policy and Outcomes writes in Forbes.

In a guest column, Bach pits two cancer drugs against each other: Pfizer's ($PFE) first-in-class lung cancer treatment Xalkori, and its brand-new competitor from Novartis ($NVS), Zykadia. They're both aimed at the same small sliver of the lung cancer market--patients whose tumors test positive for an ALK gene abnormality. And they're both pricey.

But Zykadia, which came to market second, costs more--$13,200 per month, compared with Xalkori's $11,500 per month price, a difference of about $1,700. To Bach, the two drugs are roughly comparable; we'll defer to that, because he's the expert. No reason for the price difference at the patient level, then.

Pfizer actually conducted two Phase III trials on its drug, compared with Novartis's one, Bach points out, so Novartis can't say it laid out scads more money in development than Pfizer did. Pfizer also started the process of educating doctors about ALK-positive lung cancer and the importance of diagnostic testing; in fact, company execs recently pointed out that ALK testing is on the rise, and Xalkori has benefited from that.

Why, then, the price difference? Bach posits that Novartis slapped its $13,200 price tag on Zykadia simply because it could.

Back when Xalkori first won approval, 6-figure cancer drug prices weren't so common as they are now, Bach points out. Pfizer explained its hefty price for Xalkori with some impressive response rates in a tough type of lung cancer. Plus, as a treatment for a small number of NSCLC patients, Xalkori's cost wouldn't be a huge burden, population-wise.

Now, with a host of pricey treatments on the market, Novartis's $13,200 sticker price on Zykadia doesn't sound as extreme as it might have once.

Bach says Novartis has some explaining to do. He's not a stranger to price-based debates, either. A few years ago, he and his Memorial Sloan-Kettering Cancer Center colleagues turned away Sanofi's ($SNY) brand new colon cancer drug Zaltrap, saying its 6-figure price was way too much for the benefits it conferred. In an op-ed piece in The New York Times, Bach and his co-authors explained their thinking--and suggested that more such decisions would follow.

 

Jury won't be so cavalier NVS, Buckle up

6th Circ. Revives Aredia Jaw Injury Suit Against Novartis
By Sindhu Sundar
New York (August 18, 2014, 7:38 PM ET) -- The Sixth Circuit on Monday reversed a lower court that had granted summary judgment to Novartis Pharmaceuticals Corp. in a suit that accuses the drugmaker of failing to warn the plaintiff's doctor that its bone drugs Aredia and Zometa can damage jaw bones.

A three-judge panel ruled that a jury should decide whether Novartis' alleged failure to warn caused the injuries of plaintiff Charolette Payne, who took both drugs and developed osteonecrosis of the jaw, and had to get a portion of her jaw removed

 

Judge Jane Branstetter Stranch, writing for the panel, said that, under Tennessee law, Payne’s failure to warn claim should not have been dismissed at the summary judgment stage. Read the Sixth Circuit ruling here.

The district court determined that the plaintiffs could not show that Novartis had failed to warn Payne’s doctor because he “would not have been meaningfully changed his prescribing practice had he been aware of the risk of the drugs,” according to the appellate court opinion.

The appellate court disagreed, ruling that the issue of causation is for a jury to decide. “Viewed in the light most favorable to the Paynes, a factfinder could infer that, had he known the risk, [the prescribing physician’] would have warned Payne about osteonecrosis of the jaw] before starting her on Aredia or Zometa and Payne would have then refused to take the drugs,” Stranch said.

Payne’s prescribing physician indicated, if he had been provided different warnings, he would have informed Payne that Aredia and Zometa could destroy her jawbone.

And Payne indicated she would not have taken the bisphosphonate drugs if she had known of that risk to her jaw.

Payne received the drugs as part of her treatment during her fight with breast cancer.

 

Despicable

Novartis Japan admits concealing drug side effects
AFP
Sep. 1, 2014, 9:13 AM

Tokyo (AFP) - The Japanese unit of Swiss pharma giant Novartis has admitted it did not report more than 2,500 cases of serious side effects in patients using its leukaemia and other cancer drugs, reportedly including some fatalities.

The revelations, which marked the latest in a string of scandals at the company's Japanese subsidiary, come after local authorities slapped the firm on the wrist, saying it had to clean up its operations.

On Friday, Novartis issued a statement saying it had failed to report to regulators at least 2,579 cases where patients had suffered serious potential side effects from its drugs.

Japan's Jiji Press news agency said they included some fatal cases, without specifying a figure.

The unit declined to comment on Monday, referring questions to its Swiss headquarters.

Japanese media said the number of cases involved could rise as Novartis probes 6,000 other cases.

The news comes about four months after Novartis replaced the top executives at its Japanese arm over allegations it did not properly disclose the possible side effects of its leukaemia treatments.

In July, Japanese prosecutors laid charges against the unit over claims that falsified data was used to exaggerate the benefits of a popular blood-pressure drug.

They also indicted a former employee, Nobuo Shirahashi, alleging he manipulated the data in clinical studies that were later used in marketing the drug Diovan.

 

why all the attention focused on japan?

 

In 1951, a quiet, picturesque village in southern France was suddenly and mysteriously struck down with mass insanity and hallucinations. At least five people died, dozens were interned in asylums and hundreds afflicted.

For decades it was assumed that the local bread had been unwittingly poisoned with a psychedelic mould. Now, however, an American investigative journalist has uncovered evidence suggesting the CIA peppered local food with the hallucinogenic drug LSD as part of a mind control experiment at the height of the Cold War.

...

Eventually, it was determined that the best-known local baker had unwittingly contaminated his flour with ergot, a hallucinogenic mould that infects rye grain. Another theory was the bread had been poisoned with organic mercury.

However, H P Albarelli Jr., an investigative journalist, claims the outbreak resulted from a covert experiment directed by the CIA and the US Army's top-secret Special Operations Division (SOD) at Fort Detrick, Maryland.

The scientists who produced both alternative explanations, he writes, worked for the Swiss-based Sandoz Pharmaceutical Company, which was then secretly supplying both the Army and CIA with LSD.

Mr Albarelli came across CIA documents while investigating the suspicious suicide of Frank Olson, a biochemist working for the SOD who fell from a 13th floor window two years after the Cursed Bread incident. One note transcribes a conversation between a CIA agent and a Sandoz official who mentions the "secret of Pont-Saint-Esprit" and explains that it was not "at all" caused by mould but by diethylamide, the D in LSD.

While compiling his book, A Terrible Mistake: The Murder of Frank Olson and the CIA's Secret Cold War Experiments, Mr Albarelli spoke to former colleagues of Mr Olson, two of whom told him that the Pont-Saint-Esprit incident was part of a mind control experiment run by the CIA and US army.
http://www.telegraph.co.uk/news/worldnews/europe/france/7415082/French-bread-spiked-with-LSD-in-CIA-experiment.html

 

Bye PC

Judge Favors Par In Novartis Alzheimer's Patch Patent Row
By Kurt Orzeck
Los Angeles (September 02, 2014, 8:35 PM ET) -- A Delaware federal judge on Friday found Novartis Pharmaceuticals Corp. hadn't shown Par Pharmaceutical Inc. infringed a patent for a patch that treats Alzheimer’s disease, asking the generic-name drugmaker to file a draft of a final judgment in its favor in the consolidated suit.

U.S. District Judge Richard G. Andrews decided a chemical compound detailed in Par's abbreviated new drug application for 13.3-milligram generic rivastigmine transdermal patches doesn't meet a claim requirement in Novartis' patent-at-issue, U.S. Patent Nos. 6,335,031

 

What is this all about?

 

"rots o' ruck".

 

Is Novartis' LCZ696 "revolutionary" or just a marginal improvement?

Daniel R. Hoffman, Ph.D., President, Pharmaceutical Business Research Associates
Posted: Wednesday, September 10, 2014, 1:02 PM

Over the Labor Day weekend, Novartis presented the results of a trial for its cardiovascular compound, LSC696, at the European Society of Cardiology (ESC) meeting in Barcelona, Spain. Reactions to those results were the number one topic on the pharma blogosphere for several days afterward.

Prior to the presentation, Wall Street's sales projections for the drug were in the vicinity of $1 billion per year by 2020. Immediately afterward the forecasts skyrocketed, especially among the most bullish analysts. Morningstar analyst Damien Conover raised his forecast from an annual peak of just over $1 billion to approximately $6 billion. Leerink Swann's Seamus Fernandez doubled his estimate from $3.2 billion a year to $6.4 billion. Sanford C. Bernstein's Timothy Anderson was especially exuberant, predicting annual sales as high as $8 billion.

So do these enormous sales projections for LCZ696, following its Labor Day splash, indicate that the product is a "revolutionary breakthrough" for treating heart failure, as its lead investigator calls it? Or is this just one more instance where a pharma company promotes a small, tweaked improvement as a breakthrough to justify squeezing payers for premium dollars?

First, a bit of background.

LSC696 actually combines two compounds: valsartan (which is currently sold by Novartis under the name Diovan) and the neprilysin inhibitor, sacubitril.

The valsartan works within a physiological pathway known as the RAAS cascade. Researchers classify it as an angiotensin II receptor blocker (ARB) because it opposes the action of angiotensin II, a naturally occurring substance in the body that raises blood pressure and forces the heart to work harder. ARBs help relax and widen blood vessels, thereby lowering blood pressure and making it easier for the heart to pump blood.

The sacubitril is a neprilisyn inhibitor, which means it decreases the body's neprilysin enzyme that, in turn, helps control blood volume and lower blood pressure. Given this combined mode of action, researchers call LSC696 a RAAS-NEP inhibitor.

Amid all the Wall Street drumbeating, Novartis' design for the study presented in Barcelona was the first thing that aroused skepticism. Novartis compared the new regimen to enalapril. Enalapril acts on the RAAS cascade differently than ARBs. It prevents the conversion of angiotensin I to angiotensin II. As such it is classified as an ACE inhibitor. Within this treatment group, enalapril is actually one of the oldest and weakest ACE inhibitors, having been approved in 1985 as branded Vasotec. Although matching the LCZ696 test drug/regimen against another compound is preferable to pharma's usual approach of comparing something new to placebo, a comparison to something that is less than state of the art seems to stack the deck in favor of the new medication.

Just as importantly, contributing authors in the New England Journal of Medicine pointed out that the enalapril dose used in the trials was lower than the one generally recommended. At the same time, investigators had the liberty to increase dosing on the valsartan portion of LCZ696 to its maximum level. That means Novartis' researchers may have compared a full dose of valsartan to a moderate dose of enalapril, in which case something other than LCZ696's use of a NEP inhibitor is what produced a better result. This observation is part of what led several cardiologists who attended the meeting in Barcelona to ask why LCZ696, if it represents a truly improved level of care, failed to reduce atrial fibrillation, a key characteristic of worsening heart failure.

Some observers question yet another aspect of the LSC696 study design. They point out that patients who received the Novartis test regimen had significantly lower systolic blood pressure before the study than those who received enalapril. The higher ingoing blood pressure among enalapril users may have created a more advanced cardiovascular condition that made their hospitalizations or deaths more likely.

Other cardiologists at ESC questioned the part of Novartis' study plan that included a "washout" period for patients enrolled in the trial. Investigators switched patients from the heart medications they were taking prior to the study and gave them either enalapril or the LSC696 duo before starting the trial. Those patients that could not tolerate the therapies were not enrolled. That means the incidence of side effects and other adverse events in the study was likely lower than what cardiologists would see in real world practice because the enrollment was skewed to favor patients who can tolerate valsartan+sacubitril.

After considering the study's design, a second reason for skepticism relates to interpreting the results. The press releases tout the fact that LCZ696 confers a 20% relative risk reduction versus enalapril for developing the study endpoints of heart failure hospitalization or death. What that actually means is there was a 26.5% chance for hospitalization/death with enalapril versus a 22% chance with LCZ696. Now a 4.5% smaller risk can make a huge commercial difference, because that was the approximate extent to which Plavix reduced risk versus aspirin. Plavix went on to become the world's second highest selling product behind Lipitor. Clinically and epidemiologically, however, that represents a good but not a great difference. Thirty-two people need to be treated (NNT) with LCZ696 to prevent one death and the rule of thumb is that an NNT of 50 or higher means something is fairly useless. In other words, LCZ696 may represent yet another marginal, incremental improvement rather than any sort of revolutionary breakthrough.

In addition to issues related to the study's design and interpretation, a number of cardiologists and other researchers raise an issue about sacubitril's mode of action: inhibiting the neprilysin enzyme. They fear the process could affect other metabolic pathways and produce harmful consequences. For example, some researchers argue that neprilysin seems to play a role in reducing beta-amyloid in the brain. Beta-amyloid forms the clumps and tangles characteristic of Alzheimer's disease and reducing the neprilysin enzyme may raise the risk of patients developing Alzheimer's. Novartis ended the study reported in Barcelona too early to assess such side effects.

LSC696 is not the first RAAS+NEP inhibitor promoted by its developer as something that will revolutionize the way cardiologists treat the hypertension-to-heart failure process. The same earth-shaking predictions for Bristol-Myers Squibb's omapatrilat (Vanlev) were all over the media a decade ago. Novartis's lead investigator on LSC696 is Dr. Milton Packer from the University of Texas Southwestern in Dallas. Ten years ago the same Dr. Packer, then at Columbia University in New York, was BMS’s lead investigator on Vanlev and he was equally effusive in touting that product as a revolutionary breakthrough. Alas, Vanlev never even made it to the market. The FDA decided against approving it because a number of patients in the studies developed potentially serious angioedema, a swelling of the lips and throat.

Around the same 2004-2005 timeframe, Pharmacia was developing another RAAS-NEP inhibitor, eplerenone (Inspra), one that did receive FDA approval. Nonetheless, its modest benefits led Pfizer to promptly bury Inspra as soon as they bought Pharmacia.

Is LCZ696 sufficiently different from these other RAAS-NEPs to be more effective in controlling heart failure while avoiding their side effects and safety-tolerability problems? The Novartis therapy replaces an ACE inhibitor with an ARB and it uses a different neprilisyn inhibitor. But as often happens in pharmacology, the several different compounds within a chemical class produce the same clinical effect.

Whether LCZ696 lives up to its projections for pulling in $6-8 billion a year will also depend on how Novartis prices the product. In the past, the company has been remarkably tone deaf on that factor, as witness the launch of its MS product Gilenya.

Novartis has about six or seven years all to itself for using this RAAS-NEP inhibitor before a competitor potentially can bring another one to market. That’s both an advantage and a disadvantage. The advantage of working without a competitor is obvious, but the disadvantage is that Novartis will have to generate the primary demand for a RAAS-NEP all alone. Acting by themselves, they will have to provide data that satisfactorily answer all the questions about the study. Without competing RAAS-NEP brands on the market, Novartis will be the only company looking to demonstrate and publicize better long-term outcomes that can justify premium pricing. It remains to be seen how well they will do all of this before a competitor or two come along.

Finally, it seems questionable whether any branded pharma company would pair either omapatrilat or eplerenone with an off-patent ARB and sponsor the studies needed to obtain regulatory approval. Eplerenone is already a generic and omapatrilat will likely lose patent protection this year. Nonetheless, it is worthwhile speculating whether a Teva, an Actavis or a Dr. Reddy's – all of which know how to make good margins on generics – might be willing to sponsor and conduct the studies that test how well one of them, combined with a generic ARB, treats heart failure.

If one or more generics companies did make that play, the sales projections for LCZ696 would likely fall back to what they were before Labor Day or possibly even lower.

When the FDA shot down Vanlev, some observers predicted that it was unlikely another RAAS-NEP would ever see the light of day. Perhaps the public relations Novartis manufactured for LCZ696 might provide its most important benefit if all the talk inspires the development of an all-generic medication for heart failure, one where its slightly better effect is matched by a commensurately modest price.

 

9/11/2014 @ 11:49AM

Japanese Research Scandal Involving Novartis Blood Pressure Drug Widens

The Japanese scandal over research using the Novartis blockbuster hypertension drug Diovan (valsartan) continues to widen. The first major figure brought down in the scandal was Hiroaki Matsubara, a prominent cardiologist and researcher at Kyoto Prefectural University in Japan, who resigned from his position after numerous retractions and investigations. Then last year accusations surfaced about another prominent researcher, Issei Komuro, a professor at Chiba University.

Chiba University has now completed an investigation of one of Komuro’s most important papers, the 2011 report of the Valsartan Amlodipine Randomized Trial (VART), published in Hypertension Research, which is the official journal of the Japanese Society of Hypertension. The Chiba University investigation obtained testimony from VART investigators and found multiple problems with the paper, including the surreptitious involvement of a Novartis employee. (A similar problem occurred in the Matsubara trials.) The investigation concludes that the VART paper in Hypertension Research should be retracted.

To date the journal has not retracted the paper. I am informed by a reliable source in Japan that a retraction is widely anticipated in the Japanese hypertension community. I have requested comments from the journal, Chiba University, and Novartis.

The retraction, if it comes, will not be the end of the story. The Japanese blog that originally brought the case to attention raised questions about 13 additional papers by Komuro. The papers were all published in well-known journals, including Nature, Nature Medicine, and 4 separate papers in Circulation. On many of the papers Komuro served as the senior author. It should be noted that Komuro was a co-author with Matsubara on several papers, including a Nature Medicine paper and a Circulation paper now under suspicion.

One obvious take-away lesson is that research misconduct like this has a pernicious effect on medicine and science. Another lesson may be a bit less obvious: all research needs to be viewed with a critical eye. Franz Messerli, a prominent hypertension researcher, told me that even if it had not been compromised by misconduct the VART trial should have been viewed with suspicion. VART, he said, “is a pathetic attempt in spinning and to extrapolate meager surrogate endpoint findings into powerful euphemisms such as cardioprotection and nephroprotection. Wasn’t there a study with the name of VALUE, double blind, head-to-head, with a 10 times larger patient population, sponsored by the same company, showing if anything, superiority of amlodipine over valsartan?”

 

Gold standard 30 year old Vasotec? Really? LMAO! Almost as funny as selling TKT/combo's on rat data. What a joke & seriously who trusts their trials or clinical studies?

 

hence the reason for the mck plan

 

WTF is the mck plan

 

Again....& Again

FDA slaps cardiovascular warnings on Roche/Novartis asthma blockbuster Xolair
September 29, 2014 | By Arlene Weintraub

It was way back in 2009 when the FDA first indicated it was worried about reports of heart attacks and strokes in patients taking Xolair, the asthma treatment co-marketed by Novartis ($NVS) and Roche ($RHHBY). Now the agency is taking action, slapping new warnings to the product's label confirming that it's associated with cardiovascular risks.

The warnings will not be contained in a prominent "black box" on Xolair's packaging but rather in the "Adverse Reactions" section of its label, according to an announcement from the FDA. That's the good news.

The bad news is that the warnings are somewhat scary. The FDA reviewed data from a 5-year study, along with 25 trials comparing Xolair to placebo, and determined that the drug raises the risk of problems occurring in the blood vessels of the heart and brain, including clots, heart attacks, mini-strokes, chest pain and pulmonary hypertension--high blood pressure in the lungs' arteries that can be life-threatening. Due to weaknesses in how the 5-year study was designed, however, the FDA is unable to determine exactly how big the risks are, the FDA says.

Roche and Novartis say they worked closely with the FDA on the updates. In a statement acquired by Reuters, the companies added that they were committed to patient safety and they believe "the revisions will provide healthcare professionals and their patients with the most up-to-date information to make informed healthcare decisions."