Woman Killed by a Superbug

Public health officials from Nevada are reporting on a case of a woman who died in Reno in September from an incurable infection. Testing showed the superbug that had spread throughout her system could fend off 26 different antibiotics.

The case involved a woman who had spent considerable time in India, where multi-drug-resistant bacteria are more common than they are in the US. She had broken her right femur — the big bone in the thigh — while in India a couple of years back. She later developed a bone infection in her femur and her hip and was hospitalized a number of times in India in the two years that followed. Her last admission to a hospital in India was in June of last year.

The unnamed woman — described as a resident of Washoe County who was in her 70s — went into hospital in Reno for care in mid-August, where it was discovered she was infected with what is called a CRE — carbapenem-resistant enterobacteriaceae. That’s a general name to describe bacteria that commonly live in the gut that have developed resistance to the class of antibiotics called carbapenems — an important last-line of defense used when other antibiotics fail.

CDC Director Dr. Tom Frieden has called CREs “nightmare bacteria” because of the danger they pose for spreading antibiotic resistance. In the woman’s case, the specific bacteria attacking her was called Klebsiella pneumoniae, a bug that often causes of urinary tract infections.

Testing at the hospital showed resistance to 14 drugs — all the drug options the hospital had, said Lei Chen, a senior epidemiologist with Washoe County Health District. A sample was sent to the CDC in Atlanta for further testing, which revealed that nothing available to US doctors would have cured this infection.

— source scientificamerican.com

Why People with Diabetes Can’t Buy Generic Insulin

A generic version of insulin, the lifesaving diabetes drug used by 6 million people in the United States, has never been available in this country because drug companies have made incremental improvements that kept insulin under patent from 1923 to 2014. As a result, say two Johns Hopkins internist-researchers, many who need insulin to control diabetes can’t afford it, and some end up hospitalized with life-threatening complications, such as kidney failure and diabetic coma.

In a study published March 19, 2015, in the New England Journal of Medicine, authors Jeremy Greene, M.D., Ph.D., and Kevin Riggs, M.D., M.P.H., describe the history of insulin as an example of “evergreening,” in which pharmaceutical companies make a series of improvements to important medications that extend their patents for many decades. This keeps older versions off the generic market, the authors say, because generic manufacturers have less incentive to make a version of insulin that doctors perceived as obsolete. Newer versions are somewhat better for patients who can afford them, say the authors, but those who can’t suffer painful, costly complications.

“We see generic drugs as a rare success story, providing better quality at a cheaper price,” says Greene, an associate professor of the history of medicine at the Johns Hopkins University School of Medicine and a practicing internist. “And we see the progression from patented drug to generic drug as almost automatic. But the history of insulin highlights the limits of generic competition as a framework for protecting the public health.”

More than 20 million Americans have diabetes, in which the body fails to properly use sugar from food due to insufficient insulin, a hormone produced in the pancreas. Diabetes can often be managed without drugs or with oral medications, but some patients need daily insulin injections. The drug can often cost from $120 to $400 per month without prescription drug insurance.

“Insulin is an inconvenient medicine even for people who can afford it,” says Riggs, a research fellow in general internal medicine and the Berman Institute of Bioethics at Johns Hopkins. “When people can’t afford it, they often stop taking it altogether.” Patients with diabetes who are not taking prescribed insulin come to Riggs’ and Greene’s Baltimore-area clinics complaining of blurred vision, weight loss and intolerable thirst — symptoms of uncontrolled diabetes, which can lead to blindness, kidney failure, gangrene and loss of limbs.

The two doctors decided to find out why no one makes generic insulin. A University of Toronto medical team discovered insulin in 1921, and in 1923, the university, which held the first patent, gave drug companies the right to manufacture it and patent any improvements. In the 1930s and 1940s, pharmaceutical companies developed long-acting forms that allowed most patients to take a single daily injection. In the 1970s and 1980s, manufacturers improved the purity of cow- and pig-extracted insulin. Since then, several companies have developed synthetic analogs.

Biotech insulin is now the standard in the U.S., the authors say. Patents on the first synthetic insulin expired in 2014, but these newer forms are harder to copy, so the unpatented versions will go through a lengthy Food and Drug Administration approval process and cost more to make. When these insulins come on the market, they may cost just 20 to 40 percent less than the patented versions, Riggs and Greene write.

— source hopkinsmedicine.org

Pharmaceutical Giant Threatens to Drag Government Before Corporate Tribunal

Swiss pharmaceutical giant Novartis appears to have used trade and investment agreements to launch a legal and political pressure campaign against the government of Colombia’s efforts to make a Novartis leukemia drug accessible to cancer patients.

The drug, imatinib, also known as Gleevec in the United States, is a chemotherapy medication used to treat several forms of leukemia. A preferred choice for many leukemia patients and their doctors, imatinib is designated an “essential medicine” by the World Health Organization due to its record of effectiveness and safety. The drug must be taken daily, with the duration of treatment typically a minimum of 36 months, although courses commonly continue for five or more years.

Imatinib has led global sales for Novartis, generating $4.6 billion in 2015.

Currently, the medicine costs $15,000 per patient per year in Colombia, a country with a per capita GDP of just $6,105. Colombian civil society groups asked their government to issue a compulsory license for the medicine. This would end Novartis’ current monopoly rights to produce the drug and authorize generic competition, the most effective means of reducing price. A Colombian legislative committee urged the Minister of Health to declare a matter of public interest, a key procedural step toward allowing competition from generics.

Novartis and U.S. government representatives pressured Colombia not to issue the compulsory license. Colombia instead followed a more conservative course toward modest price controls. The Colombian Ministry of Health issued the public interest declaration, but indicated that a compulsory licensing would only be employed in case of acute shortage.

Nevertheless, last year Novartis provided formal notice of a dispute against the Colombian government using the controversial Investor-State Dispute Settlement (ISDS) system under the Swiss-Colombia Bilateral Investment Treaty. That agreement includes ISDS provisions similar to those found in the North American Free Trade Agreement (NAFTA). The period for trying to resolve the dispute expired in the end of 2016. In late December 2016, the Health Ministry announced that, in accordance with the public interest, price would go down by some 44 percent. Due to the secretive nature of ISDS cases, Novartis’ next steps in the ISDS case — and the specific charges against Colombia — are unknown.

Novartis isn’t the first drug company to use the extraordinary rights in trade and investment treaties to challenge governments’ medicine pricing policies: Eli Lilly attempted to use NAFTA to demand $450 million from Canadian taxpayers over Canadian courts’ decisions that the firm’s monopoly patent rights for two drugs did not satisfy the country’s standards to obtain a patent.

ISDS empowers multinational corporations to sue governments before panels of three corporate lawyers. These corporations need only convince the corporate lawyers that a law or safety regulation violates their new investor rights. The corporate lawyers can award the corporations unlimited sums to be paid by taxpayers, including for the loss of expected future profits the corporations claim they would have earned if the domestic policy was never enacted. The corporate lawyers’ decisions are not subject to appeal and the amount they can order taxpayers to give corporations has no limit.

Public backlash against ISDS was one of the primary reasons that the Trans-Pacific Partnership (TPP) could not obtain majority support in the U.S. Congress and negotiations for a Transatlantic Trade and Investment Partnership have been sidelined.

Novartis’ threatened ISDS claim appears to be just one element of its extreme pressure tactics to strong-arm the Colombian government. A shocking, leaked letter from last year (English available here) from the Colombian Embassy in Washington, D.C., to the Colombian Minister of Foreign Affairs discusses mounting political pressure from U.S. Senate staff, the Office of the U.S. Trade Representative (USTR), and unnamed pharmaceutical companies to dissuade Colombia from moving forward to make the leukemia drug more accessible to those who needed it.

The leaked diplomatic communication warns that Colombia’s actions to lower the drug’s price could risk U.S.-Colombia relations, Colombian membership in the TPP, and trigger consequences under the 2012 Colombia-U.S. Free Trade Agreement. Threatening Colombia’s potential membership in the TPP over an access to medicines effort was particularly perverse, given that Doctors Without Borders called the TPP “the worst trade agreement for access to medicines in developing countries.”

Perhaps most disturbingly, the Colombian Embassy was sufficiently alarmed by the pressure from the United States to twice remark that it was concerned that proceeding with the compulsory license would put at risk the $450 million committed for President Obama’s support for Paz Colombia, the peace initiative working to end the devastating 50 year-long Colombian conflict that has claimed nearly a quarter of a million lives — mostly civilian.

In response, Senators Bernie Sanders (I-VT) and Sherrod Brown (D-OH) wrote to then-USTR Michael Froman, describing the situation and condemning “any efforts to intimidate and discourage Colombia’s government from taking measures to protect the public health in a way that is appropriate, effective, and consistent with the country’s trade and public health obligations.” They pointed out that “compulsory licenses are consistent with Colombia’s International trade obligations and are a legitimate means to ensuring access to medicines.”

Access to medicine experts believe that Novartis is most focused on setting a precedent in the Colombia case, rather than focused on direct financial losses with respect to the drug’s sale in Colombia. The Colombian patent for imatinib is set to expire in 2018. There are an estimated 2,000 Colombian users of imatinib. Factoring the initial 2016 Ministry proposed price cut of 50 percent (to about $7,500 per year), would yield a total difference of about $27 million over two years.

That is not an insubstantial amount of money. But in 2014, Novartis’ total revenue was $53.6 billion, twice as much as Colombia’s public and private healthcare expenditures combined (GDP for reference).

Of course, the favored refrain from pharmaceutical companies — from Mylan’s EpiPen price-gouging CEO to the infamous Martin “Pharma Bro” Shkreli — is that high profits are necessary to fund research on new drugs. However, we know that is not true across the industry. In 2014, Novartis spent nearly 50 percent more on sales and marketing than it did on research and development.

Furthermore, Novartis’s development costs for imatinib were relatively low. And Novartis did not develop imatinib on its own. Imatinib is the product of collaborations and shared funding arrangements between charities, public agencies and Novartis, which benefited from regulatory exemptions and now government-granted monopoly patents to produce the drug that facilitates billions in corporate earnings.

Novartis’ ISDS threat against Colombia is just one more example of why the expansion of corporate power via ISDS is one of the most dangerous components of our broken trade model.

Fortunately, the TPP, which would have drastically expanded ISDS liability by empowering tens of thousands of additional corporations to use the process, was defeated by thousands of diverse organizations representing working people united across borders.

But we must stop all ongoing negotiations that would expand ISDS, such as for a U.S.-China Bilateral Investment Treaty, and replace past trade and investment deals, such as NAFTA and the U.S.-Colombia pact.

The U.S. national consumer, environmental, faith, and labor coalition, Citizens Trade Campaign, lists the removal of ISDS as one of its primary demands for NAFTA replacement.

For more on ISDS, see Public Citizen’s selection of case studies of ISDS attacks against public interest protections here, and summaries of all ISDS cases under U.S. free trade agreements here.

— source citizen.typepad.com

Multidrug-resistant TB will rise in India

According to the latest issue of the journal, Multidrug Resistant-Tuberculosis (MDR-TB), a version of the disease where patients do not respond to first-line drugs, will become more common than it is now. The report projects that, by 2040, the percentage of MDR-TB will make up 32.5% of all TB cases in Russia, 12.4% of the TB cases in India, 8.9% of the TB cases in the Philippines, and 5.7% of all TB cases in South Africa. Not only does India shoulder the highest TB burden in the world, with over 2 million of the 10 million reported cases, it also accounts for the most drug-resistant patients — nearly 1.3 lakh people who do not respond to first-line drugs.

— source thehindu.com

Getting Patients Hooked On An Opioid Overdose Antidote, Then Raising The Price

First came Martin Shkreli, the brash young pharmaceutical entrepreneur who raised the price for an AIDS treatment by 5,000 percent. Then, Heather Bresch, the CEO of Mylan, who oversaw the price hike for its signature Epi-Pen to more than $600 for a twin-pack, though its active ingredient costs pennies by comparison.

Now a small Virginia company called Kaleo is joining their ranks. It makes an injector device that is suddenly in demand because of the nation’s epidemic use of opioids, a class of drugs that includes heavy painkillers and heroin.

Called Evzio, it is used to deliver naloxone, a life-saving antidote to overdoses of opioids. More than 33,000 people are believed to have died from such overdoses in 2015. And as demand for Kaleo’s product has grown, the privately held firm has raised its twin-pack price to $4,500, from $690 in 2014.

Founded by twin brothers Eric and Evan Edwards, 36, the company first sought to develop an Epi-Pen competitor, thanks to their own food allergies.

Now, they’ve taken that model and marketed it for a major public health crisis. It’s another auto-injector that delivers an inexpensive medicine.

One difference, though, is that Evzio talks users through the process as they inject naloxone. The company says the talking device is worth the price because it can guide anyone to jab an overdose victim correctly, leave the needle in for the right amount of time and potentially save his or her life.

According to Food and Drug Administration estimates, the Kaleo product, which won federal approval in 2014, accounted for nearly 20 percent of the naloxone dispensed through retail outlets between 2015 and 2016, and for nearly half of all naloxone products prescribed to patients between ages 40 and 64 — the group that comprises the bulk of naloxone users.

And the cost of generic, injectable naloxone — which has been on the market since 1971 — has been climbing. A 10-mililiter vial sold by one of the dominant vendors costs close to $150, more than double its price from even a few years ago, and far beyond the production costs of the naloxone chemical, researchers say. The other common injectable, which comes in a smaller but more potent dose, costs closer to $40, still about double its 2009 cost.

Still, experts say the device’s price surge is way out of step with production costs, and a needless drain on health-care resources.

“There’s absolutely nothing that warrants them charging what they’re charging,” said Leo Beletsky, an associate professor of law and health sciences at Northeastern University in Boston.

Kaleo, which is trying to blunt the pricing backlash and turn Evzio into the trusted brand, is dispensing its device for free — to cities, first responders and drug treatment programs. Such donations were also essential to the Epi-Pen’s business strategy.

The device has been invaluable to patients, said Eliza Wheeler of San Francisco’s Harm Reduction Coalition, a nonprofit that works to combat overdoses and has received donations of Evzio. But at $4,500 a package?

“I might have $10,000 to spend on naloxone for a year, to supply a whole city,” Wheeler said. “If I have 10 grand to spend, I certainly can’t buy two Evzios.”

Mark Herzog, Kaleo’s vice president of corporate affairs, said in an email that most earlier naloxone devices were “developed, designed and intended” for use in medically-supervised settings.

Prior kits contained a pre-filled syringe. The Evzio was the first to help laypeople dispense the drug. And competition is limited: One of the few consumer-friendly alternatives to Evzio is a nasal spray device for naloxone.

A growing market

The opioid crisis has led more experts to call for expanded access to naloxone — for people navigating addiction and for those around them. The idea is that if someone nearby could overdose, dispensing the drug should be as easy as pulling the fire alarm.

Federal and state governments have spent millions of dollars equipping police officers and other first responders with naloxone. In communities particularly hard-hit by drug overdoses, places such as schools, libraries and coffee shops are keeping the antidote on hand. Physicians are prescribing it to patients who are taking prescription painkillers in an effort to make sure they — and their families and friends — are prepared.

The Evzio could be ideal, especially when medical professionals are not nearby, noted Traci Green, an associate professor at Boston University’s School of Medicine. But the price limits access.

“It’s a really good product,” she said. “It’s elegant. People do like it — but they can’t afford it.”

“There’s a lot of value to this formulation,” said Ravi Gupta, a medical student and lead author of a December op-ed on the pricing issue, published in the New England Journal of Medicine. “But it’s not justified. This pricing is not justified.”

But consumers may not yet be pinched. In another Mylan parallel, Kaleo offers coupons to patients with private insurance, so they don’t have any co-pay when they pick up the device.

So Kaleo would say the price hikes are essentially moot. Herzog said they are necessary to subsidize programs that do not offer copayments. In a follow-up email, he added that the list price is “not a true gauge,” because insurance companies can sometimes negotiate rebates and discounts. And, he said, since the price increase, more patients have gotten Evzio prescriptions filled — so the cost doesn’t seem to be stopping them.

Mylan provides a similar Epi-Pen discount — a move that’s helped cement it as the dominant epinephrine provider. But even if consumers don’t directly pay for the price increases, they’re affected, analysts cautioned.

“When you have these kinds of programs, the cost is still borne by patients, because insurance premiums go up,” Beletsky said.

That, analysts say, undermines Kaleo’s argument that they’re somehow increasing access. After all, while some government agencies and private organizations get the drug for free or at a deep discount, that isn’t true across the board. For those who don’t get that deal, the list price matters.

Take Vermont. The state’s been particularly hard-hit by the epidemic — more than 70 people died of opioid overdose in 2015, and it’s been dubbed America’s “heroin capital.”

Its health department is trying to get naloxone into the hands of people using opioids, setting up distribution sites around the state. But because of its high cost, Evzio isn’t an option, said Chris Bell, who runs the state health department’s emergency preparedness and injury prevention division. So it is opting for the nasal spray that costs a fraction of the price.

That’s not true everywhere, though. The Veterans Health Administration, known for its especially high rate of patients taking opioid-based prescription painkillers, covers the auto-injector. It can do so, though, because of its bargaining power — the agency is legally authorized to negotiate with pharmaceutical companies.

As a result, the VA is paying “far, far less” than the Evzio list price, said Joseph Canzolino, deputy chief consultant for pharmaceutical benefits management at the VA. (He would not release the precise figure.)

The agency’s buying power is such, he added, that even when companies drive up prices, what the VA pays will stay more or less stable — far below a figure he called “pretty exorbitant.”

Thanks to an infusion of public funding to combat opioid overdoses, other institutional buyers may also be able to afford Evzios. Their budgets are larger right now, so they’re less price sensitive, said Nicholson Price, an assistant professor at the University of Michigan Law School.

But that money comes from somewhere — most likely taxpayers. And it’s hardly sustainable, Price noted, saying “at some point in time the rubber’s got to hit the road.”

Kaleo has given away more than 180,000 devices, Herzog said, distributed in 34 states among about 250 organizations such as police departments and nonprofit groups that distribute naloxone to people at risk of overdose.

Advocates and pharmacy groups have made videos touting the product. In neighborhoods where overdose is common, businesses — like fast-food restaurants, grocery stores and other retail establishments — are interested in keeping readily dispensable naloxone on hand.

But those who’ve accepted free Evzio devices and have come to rely on it may soon face withdrawal. Last year, Kaleo’s donation supply was exhausted by July. Herzog said the company has added to its donation supply and is taking applications from groups hoping for free devices.

Barring a meaningful expansion, the free device program could run out of supplies even sooner if the current opioid crisis keeps up.

The problem, law professor Price noted, is that policymakers haven’t found a solution to get people needed medication and keep pricing in line with value.

“Epi-Pen happened, and everyone was like, ‘Wow, this is terrible, we shouldn’t allow this to happen,’” he said. “And we haven’t done anything about that, and it’s not clear what the solution is. Now, shocker, it’s happening again.”

— source khn.org By Shefali Luthra

The drugs don’t work, say back pain researchers

Commonly used non-steroidal anti-inflammatory drugs used to treat back pain provide little benefit, but cause side effects, according to new research from The George Institute for Global Health.

The findings of the systematic review, published in the Annals of the Rheumatic Diseases, reveal only one in six patients treated with the pills, also known as NSAIDs, achieve any significant reduction in pain.

The study is the latest work from The George Institute questioning the effectiveness of existing medicines for treating back pain. Earlier research has already demonstrated paracetamol is ineffective and opioids provide minimal benefit over placebo.

Back pain is the leading cause of disability worldwide and is commonly managed by prescribing medicines such as anti-inflammatories. But our results show anti-inflammatory drugs actually only provide very limited short term pain relief. They do reduce the level of pain, but only very slightly, and arguably not of any clinical significance.

When you factor in the side effects which are very common, it becomes clear that these drugs are not the answer to providing pain relief to the many millions of Australians who suffer from this debilitating condition every year.

The team at The George Institute, which examined 35 trials involving more than 6000 people, also found patients taking anti-inflammatories were 2.5 times more likely to suffer from gastro-intestinal problems such as stomach ulcers and bleeding.

— source georgeinstitute.org