Deadly Medicines and Organised Crime: How Big Pharma has Corrupted Healthcare.
Thursday, June 21, 2018
The patent troll town
Texas Instruments back in 1992 sued Micron Technology for patent infringement in Marshall instead of in its hometown of Dallas.
patent troll town
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The Town That Trolls Built
The Supreme Court ruled that patent holders can no longer choose where to file infringement suits. That's bad news for Marshall, Texas.
By Joe Nocera
3
May 25, 2017, 1:41 PM CDT
Down at the old Blue Frog. Photographer; Mario Villafuerte/Bloomberg
"Do you know about the recent Supreme Court patent decision?" I asked Shawne Somerford, the proprietor of Blue Frog Restaurant and Catering in Marshall, Texas. She laughed. "Is there anybody in Marshall who doesn’t know about that patent case?" she replied.
The case in question is TC Heartland v. Kraft Foods. On Monday, the Court ruled unanimously that patent holders suing corporations can't just go hunting for a friendly court, as they've long been able to do. Instead they have to file in districts where the company is incorporated or where it has an established place of business. This is bad news for patent trolls, a.k.a. non-practicing entities, which make no products but brandish patents to sue companies for infringement.
And it's also bad news for the trolls' long-time venue of choice, the eastern district of Texas, where thousands of patent cases are brought each year — 2,500 in 2015 alone! — 95 percent of which are initiated by non-practicing entities, according to Robin Feldman, a professor at the University of California's Hastings College of the Law. The eastern district includes Tyler (population 101,000) and some patent lawsuits are filed there. But most are filed in Marshall (population 24,000), an out-of-the-way town on the eastern edge of Texas, just 20 miles from Shreveport, Louisiana. Indeed, an astonishing 25 percent of all patent litigation in the U.S. is filed in Marshall. It’s not too much to say that patent litigation is the engine that drives Marshall’s economy.
"At any given moment, there are six to ten teams of lawyers staying in Marshall," said Nathaniel Polish, of Daedalus Technology Inc., who often serves as an expert witness in patent disputes. Because the hotels, which are usually full, don’t have restaurants, locals have started cooking and catering businesses. Others serve as couriers. There has been a construction boom to create more office space. "There is a whole industry catering to the legal teams," said Polish. "They bring in a lot of money."
Before the explosion of patent lawsuits, Marshall was, like many small towns, barely hanging on, its days as a railroad and oil hub long past. Though it had a district courthouse, it was too small to even have much crime — which is exactly what appealed to Texas Instruments back in 1992 when it sued Micron Technology for patent infringement in Marshall instead of in its hometown of Dallas, where the courts were clogged with drug cases.
Texas Instruments, which had a large patent portfolio, needed a place where it could get to trial quickly. That's almost always to the advantage of plaintiffs. When the case settled within two years, with Micron agreeing to pay royalties, Texas Instruments kept bringing cases in Marshall.
By the early 2000s, Marshall had become notorious in patent circles for its "rocket docket," rules designed by a now-retired judge named T. John Ward to move patent cases along quickly. "He limited the number of pages lawyers could file in their motions, set strict timetables for hearings, and used a timer 1 to rein in lawyers’ presentations in the courtroom," Texas Monthly wrote in 2014. 2 "The procedures are set up for cases to go to trial," said one patent lawyer I spoke to. 3
Between 2001 and 2006, plaintiffs won 18 straight verdicts in Marshall, according to Texas Monthly. The combination of the rocket docket and a jury pool that seemed sympathetic to patent trolls — perhaps seeing them as little guys fighting big corporations — caused companies to seek settlements more often than not. This also amounted to a victory for the trolls because it meant that the companies were agreeing to pay them.
It also caused the American Tort Reform Association to label the eastern district of Texas one of its "judicial hellholes." (Among its complaints: "The court is viewed as favorable to so-called 'patent trolls' by refusing to dismiss meritless claims early in litigation, thereby providing claimants with greater settlement leverage.") It noted that one judge in Marshall, Rodney Gilstrap, presided over some 17 percent of all patent cases in the entire country.
In recent years, defendants have fared better in Marshall. Last year, according to Michael Smith, a Marshall lawyer who blogs about patent cases, plaintiffs barely won half of the cases that went to trial. Eastern district judges even set aside three jury verdicts in favor of plaintiffs, which Smith, in his blog, described as something that rarely happens. It probably didn’t hurt the corporate defendants that Samsung, whose lawyers are frequent visitors to Marshall, built the town an ice skating rink a few years ago. It sits directly in front of the courthouse.
On the other hand, in a case tried before Judge Gilstrap in 2015, a patent troll called Smartflash LLC won a $533 million verdict against Apple; it was overturned on appeal two months ago. And the rocket docket and all the other quirks that have made Marshall a patent-troll haven were hardly going away. As one lawyer put it to me, "In Marshall, the plaintiff is the customer."
When I asked Somerford, the owner of the Blue Frog restaurant, whether she was worried about the effect of the Supreme Court ruling on her business, she acknowledged that she was. "I don’t think it will put us out of business," she said, "but it will definitely affect our business. Catering is 50 percent of my business, and that is all related to trials."
But another Marshall resident, Samuel F. Baxter, a lawyer who often serves as local counsel in patent cases, disagreed. Asked how the loss of patent cases would affect Marshall, he said gruffly, "Not much." ("And you can quote me on that.")
He may be right. For one thing, patent trolls are already searching for ways to get around the decision. For another, it turns out that the Marshall courthouse is becoming a favored venue for a different kind of litigation that pits the little guy against big corporations: whistleblower lawsuits. All they need now is their own rocket docket.
This column does not necessarily reflect the opinion of the editorial board or Bloomberg LP and its owners.
His timer of choice was a chess clock.
The Texas Monthly story, entitled "Patently Unfair," is a good place to get a flavor of Marshall’s history as a center of patent litigation.
You will not be surprised to hear that lawyers who appear before judges in Marshall are not keen to be quoted by name.
To contact the author of this story:
Joe Nocera at jnocera3@bloomberg.net
To contact the editor responsible for this story:
Jonathan Landman at jlandman4@bloomberg.net
SLGT 2 inhibitors
SGLT Inhibitors
Jun 15, 2012
History of the sodium-glucose co-transporter (SGLT) inhibitors
by Erica Paul, PharmD, Graduate Intern University of Florida College of Pharmacy
Back in the late 1800’s, a compound called phlorizin, found in the bark of apple trees, was isolated by French chemists.
Since then it has been put to use in multiple ways, but most notably in the physiological research of renal function because of its ability to cause glucosuria. Various studies of phlorizin through the decades showed that the transporters are located in the brush border cells, that sodium is required as a co-transporter for the reabsorption of glucose, and that phlorizin is a competitive inhibitor of glucose transport. Phlorizin is non-selective, inhibiting both SGLT1 and SGLT2, so it has not held an interest as an anti-diabetic agent. It is hydrolyzed to phloretin in the gastrointestinal tract giving it poor oral bioavailability and it is potentially toxic. Fortunately, clinical studies are currently underway for selective SGLT2 inhibitors for their use as antidiabetic agents.
Sodium-Glucose Transporter 2 Inhibitors: New Therapeutic Targets, New Therapeutic Options in the Treatment of Type 2 Diabetes Mellitus. Medscape Diabetes & Endocrinology © 2008.
How they work and what they do as a new drug class
There are two primary membrane transporters that reabsorb glucose back into the blood stream. They are sodium-glucose co-transporter 1 (SGLT1) and sodium-glucose co-transporter 2 (SGLT2). SGLT1 is a high affinity, low capacity transporter requiring 1 glucose and 2 sodium molecules. Found throughout the body SGLT1 can be located in the brain, skeletal muscle, intestine, lungs, liver, and kidney. In the kidney, SGLT1 is located in the S3 segment of the proximal renal tubule contributing to less than 10% of the renal reabsorption of glucose. SGLT1 is the primary transporter of glucose in the gastrointestinal tract making it necessary for the normal absorption of dietary glucose.
Sodium-Glucose Transporter 2 Inhibitors: New Therapeutic Targets, New Therapeutic Options in the Treatment of Type 2 Diabetes Mellitus. Medscape Diabetes & Endocrinology © 2008.
SGLT2 is a low affinity, high capacity transporter requiring 1 glucose and 1 sodium molecule. It is almost exclusively found in the S1 segment of the proximal renal tubule and accounts for about 90% of the renal reabsorption of glucose. SGLT2 would be the better target to create glucosuria. There are various moieties of SGLT2 inhibitors being researched, but the two farthest along in clinical studies are C-glucosides and O-glucosides. Both of these glucoside versions are based off of the glucoside ring in phlorizin which is responsible for binding to the SGLT2 transporter. The O- and C-linked phenolic distal rings are accountable for the inhibitory properties. The addition of lipophilic groups to the distal ring enhances the transporter inhibition and increases selectivity for SGLT2 over SGLT1. The enzyme, beta-glucosidase, has a greater affinity towards the O-glucoside linked ring leading to a higher risk of hydrolysis. It is essential for the O-glucoside SGLT2 inhibitors to be developed as pro-drug esters to avoid breakdown by beta-glucosidase in the small intestine after administration. On the other hand, the C-glucoside SGLT2 inhibitors tend to be more metabolically stable, compared to the O-glucosides, and were developed to address that potential therapeutic limitation. Researchers looked at the O-glucosides, changing the bond between glucose and the agylcone moiety to a carbon-carbon bond creating the C-glucosides, making them unsusceptible to beta-glucosidase. Alternative SGLT2 inhibitors include N-glucosides, modified sugar rings, bridged ketal rings, and antisense oligonucleotides. The antisense oligonucleotides inhibit the expression of SGLT2 by binding synthesized strands of nucleic acid to the SGLT2 messenger RNA. Administration of ISIS 388626 once weekly caused an 80% reduction in renal SGLT2 mRNA expression in animal models.
Hardman TC, Dubrey SW. Development and Potential Role of Type-2 Sodium-Glucose Transporter Inhibitors for Management of Type 2 Diabetes. Diabetes Therapy (2011) 2(3):133-145.
Efficacy in Type 2 Diabetes Mellitus
Long-term HbA1c levels may not significantly be lowered in the clinical setting. Modest HbA1c lowering capabilities of 0.5%-0.9% would be comparable to currently marketed agents for glucose lowering capacity. Due to the nature of glucose excretion by blocking reabsorption, it remains to be seen whether this will result in long term benefits such as metabolic balance or weight loss. The greatest benefit appears to be when the plasma glucose concentrations are highest, for instance, during post-prandial hyperglycemia. The SGLT2 inhibitors have the potential to block 90% of glucose reabsorption by the kidney, so there is the clinical potential to excrete 160 g of glucose each day. However, the trend in the clinical studies appears to only be excreting half that amount per day. There are possible compensating mechanism theories, but the true reasoning behind this is uncertain.
Adverse Events and Complications
Since the target of SGLT2 inhibitors is so specific and the membrane transporter itself is almost exclusively known to reside in the renal tubules, the potential for cross-reaction should be low. It is unlikely SGLT2 inhibitors will induce hypoglycemia. If the plasma glucose levels are low only a small amount of glucose will be excreted in the urine. SGLT2 works independently of insulin and can be used with other antidiabetic medications with minimal risk of hypoglycemia. Even if the SGLT2 transporters are completely blocked, the SGLT1 transporters are available with a degree of glucose recovery. Due to the nature of the SGLT2 inhibitors to cause glucosuria there is the potential for increased risk of urinary tract infections (UTI). The likelihood of individuals experiencing a higher rate of UTI while on SGLT2 inhibitors needs to be looked into further. A larger amount of glucose in the urine also raises the probability of increased urine flow due to the osmotic diuretic effect.This could lead to modest reductions in blood pressure; however concerns of dehydration and loss of solutes are just as plausible. The effects look to be lower than that of loop diuretics. It is speculated that simple hydration maintenance may be all that is needed to overcome this obstacle. There is also a rare group of people with a genetic mutation that blocks the SGLT2 transporter partially or in whole. These individuals do not seem to endure any poor consequences, suggesting T2DM patients that use the SGLT2 inhibitors would not pose an immediate risk.
Current SGLT2 inhibitor clinical studies according to Clinicaltrials.gov
Drug | Sponsor | |
farxiga/Dapagliflozin | developed by Bristol-Myers Squibb in partnership with AstraZeneca | |
GW869682 | GlaxoSmithKline | |
BI 10773 | Boehringer Ingelheim Pharmaceuticals | |
TA-7284/invokana | Mitsubishi Tanabe Pharma Corporation | |
EGT0001442 | Theracos | |
EGT0001474 | Theracos | |
JNJ-28431754 | Johnson & Johnson Pharmaceutical Research & Development, L.L.C. | |
ISIS 388626 | Isis Pharmaceuticals | |
GSK189075 | GlaxoSmithKline | |
Dapagliflozin | The University of Texas Health Science Center at San Antonio |
nefariously creative tricks drug companies use to maintain monopolies
Nefariously creative tricks drug companies use to maintain monopolies.
These tricks, often played around patents, can cost the health care system — and we the insurance premium payers and taxpayers — billions.
the questionable tricks of the trade. Meet the “hard switch,” “tricks are for kids,” and “pay for delay.”
Big Pharma's Sneaky Tactic: the "Forced Switch"
Big Pharma's Sneaky Tactic: the "Forced Switch"
FacebookTwitterGoogle+More
Most recent prescription drug outrage. This time Big Pharma has taken a page from Big Insurance’s playbook, and the issue is set to go all the way to the Supreme Court. It’s called a “forced switch.”
Big Pharma wants a monopoly on your wallet
Is Big Pharma Pulling THIS Bait-and-Switch on You?
When it comes to an industry that fakes data and fights to keep lethal drugs on the market, nothing should surprise us. And yet, the idea of the “forced switch” seems unbelievable.
Here’s what happens:
New drugs are granted a patent. This means that the only one who can manufacture and market the drug is the company that created it. Patents are granted for a certain number of years, after which they expire. Once the patent expires, anyone can manufacture and market a generic version.
This is understandable. It’s intended to give drug companies time to earn back the money they spent on research and development. It’s meant to give them an incentive to keep doing research and discovering new drugs. However, once generics hit the market, the original manufacturer usually watches their profit plummet. Generics are usually 70% to 80% cheaper than the original brand name drug, and Medicare even requires pharmacies to substitute generics when they’re available in the same dosage as the brand name.
Big Pharma—it’s even sneakier than you thought
Big Pharma, of course, hates to lose this profit. Generics take a huge bite out of their bottom line and over the years they’ve tried all kinds of sneaky tactics to keep them off the market.
Once the original patent expires, manufacturers can change the dosage or how often you take a drug, then patent this “new” version. They’ve sometimes patented the same drug for two separate uses with two separate patents. They run blitz ad campaigns promoting the brand name. They offer “rewards” cards to keep you buying. They’ve even bought out the (generic) competition more than once.
But the sneakiest, most outrageous tactic they use is something the industry calls the “hard switch.” In a hard switch, the manufacturer tweaks the formula of a drug that’s about to go off-patent. Maybe they change the dosage so that you take it twice a day instead of three times, or once rather than twice. The change is usually tiny.
Is Big Pharma Pulling THIS Bait-and-Switch on You?They then patent the “new” version of the drug and start aggressively marketing it to doctors and to consumers. Then—and here’s the really sneaky part—before the patent on the original drug expires, they stop selling it. This forces people taking it to switch to the new version or do without, before it’s legal to manufacture a generic version. By the time the patent expires, most people have switched to the “new” drug already. And surprisingly, most folks will never switch to the generic, even though it’s cheaper.
It’s unethical. But is it illegal?
The New York Attorney General thought so. A handful of years ago Big Pharma player Actavis (now Allergan) decided to pull its Alzheimer’s drug, Namenda, from the market. The patent was about to expire, and Actavis didn’t want competition from generics. So it created a “new” version of the drug, called Namenda IR. The only difference? You take Namenda twice per day. You take Namenda IR once.
And somehow, as far as the law and the FDA are concerned, that makes it...a whole new drug? With a whole new patent?
This minute difference is actually patentable?
That’s downright unbelievable. But it happens. And it happens often.
Once Namenda IR was available, Actavis pulled the original off the market, forcing patients to take the new drug or do without. The New York Attorney General said this creates a monopoly—and a lower court agreed. Actavis was ordered to keep manufacturing Namenda for 60 days. Faced with losing millions of dollars in potential sales, the company appealed and the case was expected to go be heard by the Supreme Court sometime in 2016.
Not surprisingly, that never happened. The players involved finally reached a “settlement”...which didn’t settle anything except a few million dollars in a few pocket. For all practical purposes, it left the whole question wide open. There are currently several similar cases moving through the courts, so all we can do is hope that eventually the Supreme Court does weigh in and stop this underhanded practice.
But I wouldn’t hold my breath.
What does this mean for you?
Is Big Pharma Pulling THIS Bait-and-Switch on You?
It means that once again your health—and your wallet—is a pawn in Big Pharma’s game. Until and unless the Supreme Court rules that your health is more important than Big Pharma’s profits, you’re on your own.
What can you do?
Refuse to play the game. If you’re being forced to switch from one version of a drug to a “new and improved” version, do your homework. Ask questions. Read up. Find out these things:
• Is the new version really better?
• Is it going to cost you more? If so, do the benefits outweigh the cost?
• Are you being pushed to switch because a generic is about to hit the market?
• Are there other alternatives?
The fact is, there are very few drugs on the market that don’t have one or more alternatives. And a surprising amount of the time, an older (and often cheaper) medication does just as good a job as a newer, pricier one. Look into natural alternatives, too. And last of all ask yourself—and your doctor —if you really need to be taking this drug, or it’s been prescribed just because “that’s the way it’s always been done.” You might be surprised at the answer.
These tricks, often played around patents, can cost the health care system — and we the insurance premium payers and taxpayers — billions.
the questionable tricks of the trade. Meet the “hard switch,” “tricks are for kids,” and “pay for delay.”
Big Pharma's Sneaky Tactic: the "Forced Switch"
Big Pharma's Sneaky Tactic: the "Forced Switch"
FacebookTwitterGoogle+More
Most recent prescription drug outrage. This time Big Pharma has taken a page from Big Insurance’s playbook, and the issue is set to go all the way to the Supreme Court. It’s called a “forced switch.”
Big Pharma wants a monopoly on your wallet
Is Big Pharma Pulling THIS Bait-and-Switch on You?
When it comes to an industry that fakes data and fights to keep lethal drugs on the market, nothing should surprise us. And yet, the idea of the “forced switch” seems unbelievable.
Here’s what happens:
New drugs are granted a patent. This means that the only one who can manufacture and market the drug is the company that created it. Patents are granted for a certain number of years, after which they expire. Once the patent expires, anyone can manufacture and market a generic version.
This is understandable. It’s intended to give drug companies time to earn back the money they spent on research and development. It’s meant to give them an incentive to keep doing research and discovering new drugs. However, once generics hit the market, the original manufacturer usually watches their profit plummet. Generics are usually 70% to 80% cheaper than the original brand name drug, and Medicare even requires pharmacies to substitute generics when they’re available in the same dosage as the brand name.
Big Pharma—it’s even sneakier than you thought
Big Pharma, of course, hates to lose this profit. Generics take a huge bite out of their bottom line and over the years they’ve tried all kinds of sneaky tactics to keep them off the market.
Once the original patent expires, manufacturers can change the dosage or how often you take a drug, then patent this “new” version. They’ve sometimes patented the same drug for two separate uses with two separate patents. They run blitz ad campaigns promoting the brand name. They offer “rewards” cards to keep you buying. They’ve even bought out the (generic) competition more than once.
But the sneakiest, most outrageous tactic they use is something the industry calls the “hard switch.” In a hard switch, the manufacturer tweaks the formula of a drug that’s about to go off-patent. Maybe they change the dosage so that you take it twice a day instead of three times, or once rather than twice. The change is usually tiny.
Is Big Pharma Pulling THIS Bait-and-Switch on You?They then patent the “new” version of the drug and start aggressively marketing it to doctors and to consumers. Then—and here’s the really sneaky part—before the patent on the original drug expires, they stop selling it. This forces people taking it to switch to the new version or do without, before it’s legal to manufacture a generic version. By the time the patent expires, most people have switched to the “new” drug already. And surprisingly, most folks will never switch to the generic, even though it’s cheaper.
It’s unethical. But is it illegal?
The New York Attorney General thought so. A handful of years ago Big Pharma player Actavis (now Allergan) decided to pull its Alzheimer’s drug, Namenda, from the market. The patent was about to expire, and Actavis didn’t want competition from generics. So it created a “new” version of the drug, called Namenda IR. The only difference? You take Namenda twice per day. You take Namenda IR once.
And somehow, as far as the law and the FDA are concerned, that makes it...a whole new drug? With a whole new patent?
This minute difference is actually patentable?
That’s downright unbelievable. But it happens. And it happens often.
Once Namenda IR was available, Actavis pulled the original off the market, forcing patients to take the new drug or do without. The New York Attorney General said this creates a monopoly—and a lower court agreed. Actavis was ordered to keep manufacturing Namenda for 60 days. Faced with losing millions of dollars in potential sales, the company appealed and the case was expected to go be heard by the Supreme Court sometime in 2016.
Not surprisingly, that never happened. The players involved finally reached a “settlement”...which didn’t settle anything except a few million dollars in a few pocket. For all practical purposes, it left the whole question wide open. There are currently several similar cases moving through the courts, so all we can do is hope that eventually the Supreme Court does weigh in and stop this underhanded practice.
But I wouldn’t hold my breath.
What does this mean for you?
Is Big Pharma Pulling THIS Bait-and-Switch on You?
It means that once again your health—and your wallet—is a pawn in Big Pharma’s game. Until and unless the Supreme Court rules that your health is more important than Big Pharma’s profits, you’re on your own.
What can you do?
Refuse to play the game. If you’re being forced to switch from one version of a drug to a “new and improved” version, do your homework. Ask questions. Read up. Find out these things:
• Is the new version really better?
• Is it going to cost you more? If so, do the benefits outweigh the cost?
• Are you being pushed to switch because a generic is about to hit the market?
• Are there other alternatives?
The fact is, there are very few drugs on the market that don’t have one or more alternatives. And a surprising amount of the time, an older (and often cheaper) medication does just as good a job as a newer, pricier one. Look into natural alternatives, too. And last of all ask yourself—and your doctor —if you really need to be taking this drug, or it’s been prescribed just because “that’s the way it’s always been done.” You might be surprised at the answer.
Controversial researcher’s diabetes vaccine (BCG) causes improvement in small study
Controversial researcher’s diabetes vaccine causes improvement in small study
By SHARON BEGLEY @sxbegle JUNE 21, 2018
Dr. Denise Faustman of Massachusetts General Hospital
JONATHAN WIGGS/BOSTON GLOBE
A
n experimental therapy for type 1 diabetes, widely derided by mainstream diabetes researchers, lowered blood sugar levels to near normal, a small, ongoing trial found. Patients in the trial, whose blood sugar levels have remained near normal for five to eight years, take about one-third less insulin than they did before, reducing their risk of hypoglycemia, in which insulin lowers blood sugar to dangerously low levels.
The experimental treatment, a decades-old generic vaccine for tuberculosis called bacillus Calmette-Guérin (BCG), seems to alter both cellular metabolism and the immune system, said Dr. Denise Faustman of Massachusetts General Hospital, senior author of the study published Thursday in npj Vaccines. “This cheap, old vaccine is lowering blood sugar to levels never achieved before,” she said.
While the results, from only nine patients, must be replicated in a larger study, said Dr. Joseph Bellanti of Georgetown University Medical Center, “if what they found is true, they really have something here.” Bellanti, who was not involved in the research, said the study’s eight-year follow-up and use of a placebo control arm made him “cautiously optimistic” that two doses of the BCG vaccine “can decrease levels of A1c,” a measure of blood glucose that predicts the likelihood of serious complications such as stroke and kidney failure.
JDRF (formerly the Juvenile Diabetes Research Foundation), the Joslin Diabetes Center, and several university diabetes centers all declined to speak about Faustman’s results. She has been a voice in the diabetes wilderness for nearly two decades, angering the establishment diabetes community by pursuing low-tech research very different from more popular approaches, such as embryonic stem cells and immunosupression.
Critics have gone so far as to send letters to newspapers that covered her work apologizing to patients “on behalf of Dr. Faustman” for “having their expectations cruelly raised.” She has also struggled for funding, receiving much of her research support from the private Iacocca Family Foundation, rather than in federal grants.
In Faustman’s Phase 1 clinical trial, three participants with type 1 diabetes received two doses of BCG vaccine, a month apart. After the vaccine showed signs of effectiveness, an additional six patients were vaccinated five years ago, and 111 more recently. The new paper and a presentation scheduled for a meeting of the American Diabetes Association this weekend focus on the patients who have been followed for more than five years.
All of those patients who received BCG had a statistically significant change in hemoglobin A1c. A normal level is below 6. In the vaccinated patients, A1c levels fell from an average of 7.36 before the first dose to 6.18 after five years, holding almost steady at 6.65 in the eighth year. In patients receiving a sham injection, levels showed almost no change from their initial levels of 7.10: 7.07 in the fifth year and 7.22 in the eighth.
“We wanted it to be good, but we didn’t know it would be this good,” Faustman said.
All of the patients remain on insulin, she said, but less of it. They are also able to monitor their blood sugar less frequently, which can be several times an hour. (The standard of care is a continuous glucose monitor, in which a probe is inserted into the abdomen, plus an insulin pump.) “If we can gradually move people to where they can control their blood sugar, their minute-to-minute lifestyle can improve dramatically,” Faustman said.
The A1c reductions could also bring significant health benefits. Every 10 percent drop, research shows, reduces complications such as stroke and heart attack by about one-third. The BCG vaccine lowered A1c levels 9 percent to 16 percent.
The new paper describes how the BCG vaccine, which has been used for nearly 100 years against tuberculosis and is considered extremely safe, might affect diabetes. According to studies in mice, it has two effects. It alters the immune system so as to increase levels of T regulatory cells; T regs keep other immune cells in check, including those that attack the pancreas’s insulin-making cells — the root cause of type 1 diabetes. In addition, BCG alters metabolism so cells consume higher levels of glucose, drawing more of it out of the blood, in a process called aerobic glycolysis.
“The clinical effects and the proposed mechanism demonstrated are exciting and add to the emerging consensus that the BCG vaccine can have a lasting and valuable impact on the immune system,” said Dr. Mihai Netea of Radboud University Medical Center in the Netherlands, who was not involved in the study.
A Phase 2 clinical trial of BCG is currently underway at Mass. General. It is testing multiple BCG doses in 150 patients with longstanding type 1 diabetes.
Although many studies of BCG are underway around the world in diabetes and other autoimmune diseases, including multiple sclerosis, there has been little interest among U.S. researchers outside Faustman’s lab.
“There is not a lot of enthusiasm because we’re all rewarded for discovering for-profit drugs,” she said. “Potential funders come [to my lab] and ask, ‘How can we make money off this?’”
BCG, whose one licensed manufacturer in the U.S. is Merck subsidiary Organon Teknika, costs less than a dollar a dose. (Faustman used a strain made by Sanofi.) The U.S. market for insulin meters and insulin pumps is $20 billion. “With everyone thinking they need a pump and a meter if you come along with an inexpensive vaccine that can change this standard of care, of course, there will be pushback,” Faustman said.
By SHARON BEGLEY @sxbegle JUNE 21, 2018
Dr. Denise Faustman of Massachusetts General Hospital
JONATHAN WIGGS/BOSTON GLOBE
A
n experimental therapy for type 1 diabetes, widely derided by mainstream diabetes researchers, lowered blood sugar levels to near normal, a small, ongoing trial found. Patients in the trial, whose blood sugar levels have remained near normal for five to eight years, take about one-third less insulin than they did before, reducing their risk of hypoglycemia, in which insulin lowers blood sugar to dangerously low levels.
The experimental treatment, a decades-old generic vaccine for tuberculosis called bacillus Calmette-Guérin (BCG), seems to alter both cellular metabolism and the immune system, said Dr. Denise Faustman of Massachusetts General Hospital, senior author of the study published Thursday in npj Vaccines. “This cheap, old vaccine is lowering blood sugar to levels never achieved before,” she said.
While the results, from only nine patients, must be replicated in a larger study, said Dr. Joseph Bellanti of Georgetown University Medical Center, “if what they found is true, they really have something here.” Bellanti, who was not involved in the research, said the study’s eight-year follow-up and use of a placebo control arm made him “cautiously optimistic” that two doses of the BCG vaccine “can decrease levels of A1c,” a measure of blood glucose that predicts the likelihood of serious complications such as stroke and kidney failure.
JDRF (formerly the Juvenile Diabetes Research Foundation), the Joslin Diabetes Center, and several university diabetes centers all declined to speak about Faustman’s results. She has been a voice in the diabetes wilderness for nearly two decades, angering the establishment diabetes community by pursuing low-tech research very different from more popular approaches, such as embryonic stem cells and immunosupression.
Critics have gone so far as to send letters to newspapers that covered her work apologizing to patients “on behalf of Dr. Faustman” for “having their expectations cruelly raised.” She has also struggled for funding, receiving much of her research support from the private Iacocca Family Foundation, rather than in federal grants.
In Faustman’s Phase 1 clinical trial, three participants with type 1 diabetes received two doses of BCG vaccine, a month apart. After the vaccine showed signs of effectiveness, an additional six patients were vaccinated five years ago, and 111 more recently. The new paper and a presentation scheduled for a meeting of the American Diabetes Association this weekend focus on the patients who have been followed for more than five years.
All of those patients who received BCG had a statistically significant change in hemoglobin A1c. A normal level is below 6. In the vaccinated patients, A1c levels fell from an average of 7.36 before the first dose to 6.18 after five years, holding almost steady at 6.65 in the eighth year. In patients receiving a sham injection, levels showed almost no change from their initial levels of 7.10: 7.07 in the fifth year and 7.22 in the eighth.
“We wanted it to be good, but we didn’t know it would be this good,” Faustman said.
All of the patients remain on insulin, she said, but less of it. They are also able to monitor their blood sugar less frequently, which can be several times an hour. (The standard of care is a continuous glucose monitor, in which a probe is inserted into the abdomen, plus an insulin pump.) “If we can gradually move people to where they can control their blood sugar, their minute-to-minute lifestyle can improve dramatically,” Faustman said.
The A1c reductions could also bring significant health benefits. Every 10 percent drop, research shows, reduces complications such as stroke and heart attack by about one-third. The BCG vaccine lowered A1c levels 9 percent to 16 percent.
The new paper describes how the BCG vaccine, which has been used for nearly 100 years against tuberculosis and is considered extremely safe, might affect diabetes. According to studies in mice, it has two effects. It alters the immune system so as to increase levels of T regulatory cells; T regs keep other immune cells in check, including those that attack the pancreas’s insulin-making cells — the root cause of type 1 diabetes. In addition, BCG alters metabolism so cells consume higher levels of glucose, drawing more of it out of the blood, in a process called aerobic glycolysis.
“The clinical effects and the proposed mechanism demonstrated are exciting and add to the emerging consensus that the BCG vaccine can have a lasting and valuable impact on the immune system,” said Dr. Mihai Netea of Radboud University Medical Center in the Netherlands, who was not involved in the study.
A Phase 2 clinical trial of BCG is currently underway at Mass. General. It is testing multiple BCG doses in 150 patients with longstanding type 1 diabetes.
Although many studies of BCG are underway around the world in diabetes and other autoimmune diseases, including multiple sclerosis, there has been little interest among U.S. researchers outside Faustman’s lab.
“There is not a lot of enthusiasm because we’re all rewarded for discovering for-profit drugs,” she said. “Potential funders come [to my lab] and ask, ‘How can we make money off this?’”
BCG, whose one licensed manufacturer in the U.S. is Merck subsidiary Organon Teknika, costs less than a dollar a dose. (Faustman used a strain made by Sanofi.) The U.S. market for insulin meters and insulin pumps is $20 billion. “With everyone thinking they need a pump and a meter if you come along with an inexpensive vaccine that can change this standard of care, of course, there will be pushback,” Faustman said.
Drug companies are thwarting competition
The promise of generic medications is getting further from reality each day. As the U.S. Senate considers President Donald Trump’s choice to head the Food and Drug Administration, now is the time refocus efforts on generic drugs.
How generics are supposed to work
The 1984 Drug Price Competition and Patent Term Restoration Act gave pharmaceutical companies exclusive protections for innovating a new drug. If they brought a new therapy to life, they enjoyed patent protection to effectively monopolize the market. That was the payoff for shouldering the high risk and high costs of developing new drugs.
But once the patent and the exclusive hold on the market expires, the legislation encouraged competition to benefit consumers. Any drug company would be able to manufacture non-brand name versions of the very same drug, so-called “generics.” And for a while, the system worked well.
Not anymore. The system intended to reward drug companies for their innovations, but eventually protect consumers, is systematically being broken. Drug companies are thwarting competition through a number of tactics, and the result is high prices, little to no competition, and drug quality problems.
The ways companies stop generics
One of the ways branded drug manufacturers prevent competition is simple: cash. In so-called “pay for delay” agreements, a brand drug company simply pays a generic company not to launch a version of a drug. The Federal Trade Commission estimates these pacts cost U.S. consumers and taxpayers $3.5 billion in higher drug costs each year.
“Citizen petitions” offer drug companies another way to delay generics from being approved. These ask the Food and Drug Administration to delay action on a pending generic drug application. By law, the FDA is required to prioritize these petitions. However, the citizens filing concerns are not individuals, they’re corporations. The FDA recently said branded drug manufacturers submitted 92% of all citizen petitions. Many of these petitions are filed near the date of patent expiration, effectively limiting potential competition for another 150 days.
“Authorized generics” are another tactic to limit competition. These aren’t really generic products at all; they are the same product sold under a generic name by the company that sells the branded drug. Why? By law, the first generic company to market a drug gets an exclusivity period of 180 days. During this time, no other companies can market a generic product. But the company with the expiring patent is not barred from launching an “authorized generic.” By selling a drug they’re already making under a different name, pharmaceutical firms are effectively extending their monopoly for another six months.
Another way pharmaceutical firms are thwarting generics is by restricting access to samples for testing. Generic drug makers need to be able to purchase a sample of a brand-name product to conduct bioequivalence testing. That’s because they have to prove they can make a bioequivalent product following the current good manufacturing practices (CGMP) standard. These manufacturers don’t need to conduct clinical trials like the original drug company did.
But the original drug developer often declines to sell drug samples to generics manufacturers by citing “FDA requirements,” by which they mean the agency’s Risk Evaluation and Mitigation Strategies program. The idea behind this program is a good one: give access to patients who will benefit from these personalized medicines, and bar access for patients who won’t benefit and could be seriously harmed. However, brand drug makers are citing these requirements for the sole purpose of keeping generics from coming to market.
Problems with generic drug makers
Although makers of a branded drug are using a variety of tactics to create barriers to healthy competition, generic drug companies are often not helping their own case. In 2015, there were 267 recalls of generic drug products—more than one every other day. These recalls are for quality issues such as products not dissolving properly, becoming contaminated, or even being outright counterfeits.
A few high-profile recalls have shaken the belief that generic drugs are truly the same. In 2014, the FDA withdrew approval of Budeprion XL 300 — Teva’s generic version of GlaxoSmithKline’s Wellbutrin XL. Testing showed the drug did not properly release its key ingredient, substantiating consumers’ claims that the generic was not equivalent. In addition, concerns about contaminated generic Lipitor caused the FDA to launch a $20 million initiative to test generic products to ensure they are truly therapeutically equivalent.
In some cases, patent law also collides with the FDA’s manufacturing rules. For example, the Novartis patent for Diovan expired in 2012. Ranbaxy received exclusivity for 180 days for the first generic product. However, due to poor quality manufacturing, Ranbaxy couldn’t obtain final FDA approval for its generic version. The FDA banned shipments of Ranbaxy products to the United States. Ranbaxy ended up paying a $500 million fine, the largest penalty paid by a generic firm for violations.
Due to these protracted problems with the company that had won exclusivity, a generic product did not become available until 2014. The two-year delay cost Medicare and Medicaid at least $900 million. Ranbaxy’s poor-quality manufacturing also delayed other key generic products like Valcyte and Nexium. Ironically, it was Mylan—involved in its own drug pricing scandal over its EpiPen allergy-reaction injector—that filed the first lawsuit to have the FDA strip Ranbaxy of its exclusivity. Mylan made multiple attempts to produce generic products but was overruled in the courts.
Ways to Fix the System
Pharmaceutical firms are currently using a set of tactics to make their temporary monopolies semi-permanent. Eliminating these tactics will not be easy. Still, doing so will fulfill the deal that policy makers offered to drug makers and consumers: a temporary monopoly on sales to help pay for drug development.
First, restrictive distribution programs need to be stopped. Generic companies must also be allowed to purchase samples of these medications to conduct bioequivalence studies. (One measure to close these loopholes already has bipartisan support.) Next, pay-for-delay agreements should be eliminated as well as a corporation’s ability to issue citizen petitions with the intent of delaying generic competition.
Encouraging and enforcing high-quality standards for medications must also be an industry imperative. To create transparency around drug quality, the FDA has proposed a system of letter grades for manufacturers. In an economic study, one official notes that lack of transparency “may have produced a market situation in which quality problems have become sufficiently common and severe to result in drug shortages.”
Another way to achieve greater transparency in medication quality is to change the product labeling laws. Labels should disclose the medication’s manufacturer. Currently, hospitals and pharmacies don’t always know which company actually made the product. This makes it difficult to base purchase decisions on quality.
Generic medications can provide great benefits for patients and health systems when there is adequate competition and quality. But their promise is unfulfilled, and it’s costing consumers.
How generics are supposed to work
The 1984 Drug Price Competition and Patent Term Restoration Act gave pharmaceutical companies exclusive protections for innovating a new drug. If they brought a new therapy to life, they enjoyed patent protection to effectively monopolize the market. That was the payoff for shouldering the high risk and high costs of developing new drugs.
But once the patent and the exclusive hold on the market expires, the legislation encouraged competition to benefit consumers. Any drug company would be able to manufacture non-brand name versions of the very same drug, so-called “generics.” And for a while, the system worked well.
Not anymore. The system intended to reward drug companies for their innovations, but eventually protect consumers, is systematically being broken. Drug companies are thwarting competition through a number of tactics, and the result is high prices, little to no competition, and drug quality problems.
The ways companies stop generics
One of the ways branded drug manufacturers prevent competition is simple: cash. In so-called “pay for delay” agreements, a brand drug company simply pays a generic company not to launch a version of a drug. The Federal Trade Commission estimates these pacts cost U.S. consumers and taxpayers $3.5 billion in higher drug costs each year.
“Citizen petitions” offer drug companies another way to delay generics from being approved. These ask the Food and Drug Administration to delay action on a pending generic drug application. By law, the FDA is required to prioritize these petitions. However, the citizens filing concerns are not individuals, they’re corporations. The FDA recently said branded drug manufacturers submitted 92% of all citizen petitions. Many of these petitions are filed near the date of patent expiration, effectively limiting potential competition for another 150 days.
“Authorized generics” are another tactic to limit competition. These aren’t really generic products at all; they are the same product sold under a generic name by the company that sells the branded drug. Why? By law, the first generic company to market a drug gets an exclusivity period of 180 days. During this time, no other companies can market a generic product. But the company with the expiring patent is not barred from launching an “authorized generic.” By selling a drug they’re already making under a different name, pharmaceutical firms are effectively extending their monopoly for another six months.
Another way pharmaceutical firms are thwarting generics is by restricting access to samples for testing. Generic drug makers need to be able to purchase a sample of a brand-name product to conduct bioequivalence testing. That’s because they have to prove they can make a bioequivalent product following the current good manufacturing practices (CGMP) standard. These manufacturers don’t need to conduct clinical trials like the original drug company did.
But the original drug developer often declines to sell drug samples to generics manufacturers by citing “FDA requirements,” by which they mean the agency’s Risk Evaluation and Mitigation Strategies program. The idea behind this program is a good one: give access to patients who will benefit from these personalized medicines, and bar access for patients who won’t benefit and could be seriously harmed. However, brand drug makers are citing these requirements for the sole purpose of keeping generics from coming to market.
Problems with generic drug makers
Although makers of a branded drug are using a variety of tactics to create barriers to healthy competition, generic drug companies are often not helping their own case. In 2015, there were 267 recalls of generic drug products—more than one every other day. These recalls are for quality issues such as products not dissolving properly, becoming contaminated, or even being outright counterfeits.
A few high-profile recalls have shaken the belief that generic drugs are truly the same. In 2014, the FDA withdrew approval of Budeprion XL 300 — Teva’s generic version of GlaxoSmithKline’s Wellbutrin XL. Testing showed the drug did not properly release its key ingredient, substantiating consumers’ claims that the generic was not equivalent. In addition, concerns about contaminated generic Lipitor caused the FDA to launch a $20 million initiative to test generic products to ensure they are truly therapeutically equivalent.
In some cases, patent law also collides with the FDA’s manufacturing rules. For example, the Novartis patent for Diovan expired in 2012. Ranbaxy received exclusivity for 180 days for the first generic product. However, due to poor quality manufacturing, Ranbaxy couldn’t obtain final FDA approval for its generic version. The FDA banned shipments of Ranbaxy products to the United States. Ranbaxy ended up paying a $500 million fine, the largest penalty paid by a generic firm for violations.
Due to these protracted problems with the company that had won exclusivity, a generic product did not become available until 2014. The two-year delay cost Medicare and Medicaid at least $900 million. Ranbaxy’s poor-quality manufacturing also delayed other key generic products like Valcyte and Nexium. Ironically, it was Mylan—involved in its own drug pricing scandal over its EpiPen allergy-reaction injector—that filed the first lawsuit to have the FDA strip Ranbaxy of its exclusivity. Mylan made multiple attempts to produce generic products but was overruled in the courts.
Ways to Fix the System
Pharmaceutical firms are currently using a set of tactics to make their temporary monopolies semi-permanent. Eliminating these tactics will not be easy. Still, doing so will fulfill the deal that policy makers offered to drug makers and consumers: a temporary monopoly on sales to help pay for drug development.
First, restrictive distribution programs need to be stopped. Generic companies must also be allowed to purchase samples of these medications to conduct bioequivalence studies. (One measure to close these loopholes already has bipartisan support.) Next, pay-for-delay agreements should be eliminated as well as a corporation’s ability to issue citizen petitions with the intent of delaying generic competition.
Encouraging and enforcing high-quality standards for medications must also be an industry imperative. To create transparency around drug quality, the FDA has proposed a system of letter grades for manufacturers. In an economic study, one official notes that lack of transparency “may have produced a market situation in which quality problems have become sufficiently common and severe to result in drug shortages.”
Another way to achieve greater transparency in medication quality is to change the product labeling laws. Labels should disclose the medication’s manufacturer. Currently, hospitals and pharmacies don’t always know which company actually made the product. This makes it difficult to base purchase decisions on quality.
Generic medications can provide great benefits for patients and health systems when there is adequate competition and quality. But their promise is unfulfilled, and it’s costing consumers.
De Ja vu ICQ group video chat and WhatsApp group video call feature
A History of Video Calling
I used it when it was first available 2 decades ago.
This the classic example of Old wine in a new bottle
ICQ was one of the original wunderkinds of the internet age. It was created and released by four Israeli high school kids, and went on to rival the world’s largest messaging apps. It predated the messaging services of AOL and Yahoo, and grew so quickly in popularity it was bought by AOL for $400 million just two years after its launch.
And there begins a strange history of continued innovation largely left unsupported by ownership. AOL never dropped its own messaging service, creating a conflict of interest, and when its fortunes dipped in the early Millennium years ICQ went with them.
It lingered on in virtual anonymity, still striking a number of firsts–including voice chats in 2003, SMS links between phones and PCs, early peer-to-peer development, and early adoption of integration with Facebook, Twitter, and the emerging social networks–before it was sold to the Russian group in 2010 for less than $200 million.
It’s a pity ICQ never enjoyed the success its early progress suggested was its destiny, but it is still remarkable that so seminal a work continues to exist at all. Vine lasted four years, AOL fell from grace long ago, and Nintendo has had its share of wilderness years, while ICQ still keeps drawing breath.
It’s a pity ICQ never enjoyed the success its early progress suggested was its destiny, but it is still remarkable that so seminal a work continues to exist at all. Vine lasted four years, AOL fell from grace long ago, and Nintendo has had its share of wilderness years, while ICQ still keeps drawing breath.
want to pay 10 $ for salt water spray ? Licefree Spray Instant Head Lice Treatment - 6 Fl Oz
states it's ingredients are
Active ingredients
Natrum Muriaticum 2X (Sodium Chloride, USP).Purpose
Purpose: Pediculicide.Uses
For the treatment of head lice; pubic (crab) lice; body lice.Warnings
Ask a doctor before use if
Ask a doctor before use if you have infestation of eyebrows or eyelashes.Stop use and ask a doctor if
skin irritation or infection is present or develops.
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