Cancer patients’ grey hair unexpectedly darkens in drug study

Fourteen patients in the study found that their grey hair darkened after taking the new drugs. Photograph: Barry Diomede/Alamy

A group of cancer patients’ grey hair has unexpectedly darkened after they took new types of drugs, researchers have revealed.

Chemotherapy is known to make patients’ hair fall out, but the 14 people involved were all being treated with new immunotherapy drugs that work differently and have different side effects from chemotherapy. A Spanish study suggests those may include restoring hair pigment, at least in patients with lung cancer.

Noelia Rivera, a dermatologist at Autonomous University of Barcelona, said they thought it could be an isolated case when it happened with the first patient. But the research team found the same thing when they asked other patients for photographs of themselves from before treatment.

The 14 people were among 52 patients with lung cancer being followed to see whether they developed bad side effects from the drugs — Keytruda, Opdivo and Tecentriq.

While most patients did not have a hair colour change, the 14 cases suggest it is not an isolated finding. In 13 patients, hair turned darkish brown or black; in one patient, it turned black in patches.

The same drugs have been linked previously with hair losing colour in patients with another cancer, melanoma.

All but one of the 14 patients in the Spanish study responded better to treatment than other patients, suggesting that hair darkening might be an indication that the drugs are working, the researchers said.

Rivera said they were continuing with the study to search for an explanation.

“It’s a fascinating report – one of those things that comes out of the blue,” said June Robinson, a Northwestern University research professor in dermatology. Robinson is also editor of the medical journal JAMA Dermatology, which published the study online this month.

She said the results deserved a deeper look but cautioned that it was too soon to suggest that they might lead to new treatments for unwanted grey hair.

Rivera noted that the drugs used in the study had serious side effects that made them unsafe for healthy people. But if it is confirmed that they do change hair colour, a different drug could be developed to treat grey hair, she said.

The pharmaceutical industry has previously capitalised on unexpected drug side effects. Examples include the male pattern baldness drug Propecia, the eyelash growing drug Latisse, and Botox anti-wrinkle injections. Active ingredients in these drugs were initially approved to treat enlarged prostates, eye pressure problems, and eye muscle spasms.

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A progressive approach to drug addiction

Instead of overlooking the true issue of drug addiction in Chatham-Kent and participating in the stigma that surrounds it, our community must be proactive. Now is our opportunity to help individuals suffering from drug addiction and prevent needless overdoses while simultaneously protecting public health.

Last year in Canada there were 2458 opioid related overdose deaths (two every day in Ontario), all which were preventable. Some readers may turn a blind eye to this statistic and argue, “who cares?” and “better for the rest of us”. My question for those people is, when did we lose our sense of community? When did we become so individualistic that our judgment of others has clouded our ability to feel empathy?

With the recent amendments to Bill C-37 put in place by our Liberal government, which makes the process of applying for safe consumption sites easier, now is the time to counterattack the rising opioid trend and provide drugs users with a safe injection site.

Opioid use in Chatham-Kent affects a significant portion of our population and heavier drugs such as heroin and methamphetamine are becoming the norm. Before this trend escalates, we must follow the lead of our major Canadian cities (Vancouver and Toronto) and advocate for a safe consumption site in Chatham-Kent to provide a more progressive approach to drug addiction.

“Insite”, which is the name of Vancouver’s site, last year alone had 1,781 overdose interventions saving the lives of suffering individuals. Yes, they are suffering. Because of the stigma that surrounds drug addiction, this may seem like a waste of money and resources to many in our community. But to reiterate, these individuals are struggling, many from mental illnesses, and are continually chastised for not having the “normal” coping mechanisms to control their lives. This safe injection site would allow for accessible, sanitary and safe means of using illicit substances, as well as provide a friendly environment free of judgment for staff members to actively engage with drug users. Having staff onsite trained in harm reduction techniques would allow addicts access to learn new strategies, be connected to other treatment services, and provide a glimpse of hope for them to realize their potential to overcome their addiction.

You may still feel this idea of allowing people to use illegal drugs in an organized legal facility is ludicrous. Won’t this encourage drug use?

Statistics have shown in Vancouver that there has not been a substantial increase in drug use because of the opening of the legal injection site. The truth of the matter is that a safe consumption site is a radical idea. It does contradict the majority of our community’s thoughts toward drug addicts. But this facility would approach the issue of drug use in a humane manner treating them as people, not outcasts of society. By providing a safe injection site, Chatham-Kent can confront the opioid crisis before it becomes an epidemic in our own backyard.


Puma Biotech Jumps On Breast Cancer Drug Approval

Leerink’s Michael Schmidt and Varun Kumarreiterated an Outperform rating on the stock today, writing that while the approval isn’t a surprise, it has removed an overhang for the stock, and it came in earlier than expected to boot.

More detail from their note:

The product label looks broad, not restricting use to specific patient populations (e.g., hormone-receptor [HR] positive patients) and there is no black box warning. The prescribing information contains fairly detailed information about the use of antidiarrheal prophylaxis measures, providing specific information on how to manage the drug’s main side effect. Information on pricing and launch timing is not available yet; PBYI previously guided to a cost of therapy that is similar to that of other breast cancer drugs. We’d expect a US launch not immediately given that PBYI has hired a US sales force only contingent on obtaining regulatory approval. A recommendation from the European CHMP is still pending and expected later this month or next. We currently model $1.3Bn US Nerlynx peak sales in the extended adjuvant treatment setting based on relatively conservative assumptions and believe 2018E Street consensus of $215M should be achievable.


“It’s raining needles”: Drug crisis creates danger to public, environment

Activist Rocky Morrison, founder of the “Clean River Project” in Lowell, Massachusetts, holds up a fish bowl filled with used hypodermic needles found in 2016. Morrison leads a clean-up effort along the Merrimack River, which winds through Lowell.


They hide in weeds along hiking trails and in playground grass. They wash into rivers and float downstream to land on beaches. They pepper baseball dugouts, sidewalks and streets. Syringes left by drug users amid the heroin crisis are turning up everywhere.

In Portland, Maine, officials have collected more than 700 needles so far this year, putting them on track to handily exceed the nearly 900 gathered in all of 2016. In March alone, San Francisco collected more than 13,000 syringes, compared with only about 2,900 the same month in 2016.

People, often children, risk getting stuck by discarded needles, raising the prospect they could contract blood-borne diseases such as hepatitis or HIV or be exposed to remnants of heroin or other drugs.

It’s unclear whether anyone has gotten sick, but the reports of children finding the needles can be sickening in their own right. One 6-year-old girl in California mistook a discarded syringe for a thermometer and put it in her mouth; she was unharmed.

“I just want more awareness that this is happening,” said Nancy Holmes, whose 11-year-old daughter stepped on a needle in Santa Cruz, California, while swimming. “You would hear stories about finding needles at the beach or being poked at the beach. But you think that it wouldn’t happen to you. Sure enough.”

They are a growing problem in New Hampshire and Massachusetts, two states that have seen many overdose deaths in recent years.

“We would certainly characterize this as a health hazard,” said Tim Soucy, health director in Manchester, New Hampshire’s largest city, which collected 570 needles in 2016, the first year it began tracking the problem. It has found 247 needles so far this year.

Needles turn up in places like parks, baseball diamonds, trails and beaches – isolated spots where drug users can gather and attract little attention, and often the same spots used by the public for recreation. The needles are tossed out of carelessness or the fear of being prosecuted for possessing them.

One child was poked by a needle left on the grounds of a Utah elementary school. Another youngster stepped on one while playing on a beach in New Hampshire.

Even if adults or children don’t get sick, they still must endure an unsettling battery of tests to make sure they didn’t catch anything. The girl who put a syringe in her mouth was not poked but had to be tested for hepatitis B and C, her mother said.

Some community advocates are trying to sweep up the pollution.

Rocky Morrison leads a cleanup effort along the Merrimack River, which winds through the old milling city of Lowell, Massachusetts, and has recovered hundreds of needles in abandoned homeless camps that dot the banks, as well as in piles of debris that collect in floating booms he recently started setting.

He has a collection of several hundred needles in a fishbowl, a prop he uses to illustrate that the problem is real and that towns must do more to combat it.

“We started seeing it last year here and there. But now, it’s just raining needles everywhere we go,” said Morrison, a burly, tattooed construction worker whose Clean River Project has six boats working parts of the 117-mile (188-kilometer) river.

In Santa Cruz, California, the community group Take Back Santa Cruz has reported finding more than 14,500 needles in the county over the past 4 1/2 years. It says it has received reports of 12 people getting stuck, half of them children.

  • Why Ohio lawmaker wants emergency responders to ignore overdose calls

“It’s become pretty commonplace to find them. We call it a rite of passage for a child to find their first needle,” said Gabrielle Korte, a member of the group’s needle team. “It’s very depressing. It’s infuriating. It’s just gross.”

Some experts say the problem will ease only when more users get treatment and more funding is directed to treatment programs.

Others are counting on needle exchange programs, now present in more than 30 states, or the creation of safe spaces to shoot up – already introduced in Canada and proposed by U.S. state and city officials from New York to Seattle.

Studies have found that needle exchange programs can reduce pollution, said Don Des Jarlais, a researcher at the Icahn School of Medicine at Mount Sinai, in New York.

But Morrison and Korte complain poor supervision at needle exchanges will simply put more syringes in the hands of people who may not dispose of them properly.

After complaints of discarded needles, Santa Cruz County took over its exchange from a nonprofit in 2013 and implemented changes. It did away with mobile exchanges and stopped allowing drug users to get needles without turning in an equal number of used ones, said Jason Hoppin, a spokesman for the Santa Cruz County.

Along the Merrimack, nearly three dozen riverfront towns are debating how to stem the flow of needles. Two regional planning commissions are drafting a request for proposals for a cleanup plan. They hope to have it ready by the end of July.

“We are all trying to get a grip on the problem,” said Haverhill Mayor James Fiorentini. “The stuff comes from somewhere. If we can work together to stop it at the source, I am all for it.”

Here’s what to do if you find a needle:

  • Don’t pick it up. You could get infected.
  • Call the proper authorities to come pick it up. Call a drug hotline or your local health department. Don’t call 911 unless there is a health risk, imminent danger, or an emergency.
  • If you opt to discard of it yourself (which is not advised), minimize hand contact. Use sturdy gloves, disposable tongs, a shovel or dustpan, and put needles in a puncture-proof container.
  • If you get poked, don’t suck the wound. Go immediately to your doctor, emergency room, or urgent care and ask about medical tests and immunizations.
  • Tell your kids about needle stick risks. Show them what a syringe looks like and use age-appropriate language to describe why they should stay away from it. Tell them if they see any needles to find an adult, who should follow the steps described above.



New Study Shows This Common OTC Pain Reliever Has a Really Scary Side Effect

Ibuprofen, a common over-the-counter pain reliever, has a troubling side-effect that’s often overlooked, but new findings have proved it’s more important to know about this now than ever before. Recent evidence found that non-steroidal anti-inflammatory drugs (NSAIDs), like ibuprofen, can increase your chances of having a heart attack in as little as one week of continuous use.

In a recent study published in the British Medical Journal, data from almost 450,000 people, 61,460 of whom had suffered a heart attack, was analyzed looking for the effect over time of taking three common anti-inflammatory painkillers: ibuprofen, diclofenac and naproxen. The data revealed that compared with people who didn’t take the painkillers, those who did ingest them had a 20 percent to 50 percent increased risk of having a heart attack.

Additionally, the risk was found to be higher for people who ingested 1,200 mg a day of ibuprofen (about six tablets of Advil) and 750 mg a day for naproxen (about three and a half Aleves), Yahoo! reports. The study reported that it only took a week for a higher risk of heart attack to set in on a person, with the highest risk occurring at about a month of usage. After a month, researchers found that the risk didn’t increase further but rather stayed the same.

Typically, NSAIDs are safe when used correctly for mild pain relief, however, many people have begun relying on NSAIDs for prolonged periods of time at a higher dosage to treat their pain, which is why the risk of heart attack associated with the use of NSAIDs has begun to rise.

While this study certainly revealed a scary truth about the drug, it’s important to note that taking an NSAID for minor pain relief at the lowest effective dose and a minimal length of time isn’t likely to cause aheart attack. It’s the usage level over a longer time period at higher dosage that can be dangerous, so it’s best to limit your use as much as possible to avoid any unwanted negative side effects.





Price Transparency Is Critical to Drug Pricing Solutions

Prescription drug costs are a hot political issue, not as much because of the share of the U.S. health care dollar they consume but because consumers pay a larger share of their drug costs out of pocket than they do for other health care.

The lack of price transparency for prescription drugs is a large part of the problem, and making pricing more transparent throughout the process could help in finding viable solutions.

About 10% of overall health spending in the U.S. goes to prescription drugs, dwarfed by the 32% spent on hospitals and 26% on physician, dental, and other clinical services, according to National Health Expenditure data.

But more of the costs for prescription drugs are shifted to consumers than for other health costs.

Under a typical plan, consumers pay a $20-$30 copayment for physician visits and $250 for a hospital stay.  But the complex charges for prescription drugs often range from co-payments of $15 – $100 for “preferred” drugs to 45% or more of the cost of specialty or non-preferred drugs.

Consumers therefore experience more out-of-pocket costs for medicines while a greater share of other, likely more-expensive, medical expenditures is run through insurance.

A huge system of drug rebates and discountshappens behind the scenes in the pharmaceutical supply chain, further distorting the market and confusing consumers about the actual price of a drug. Only a trickle of these discounts and rebates actually reaches the consumer.

Even though rebates paid by biopharmaceutical companies can substantially reduce the prices insurers and pharmacy benefit managers (PBMs) pay for brand medicines, insurers use list prices—rather than discounted prices—to determine how much to charge patients when they pay their share, further increasing what consumers pay.

A survey by the National Community Pharmacists Association taken in early June looked at these behind-the-scenes pricing deals.  “One pharmacist told surveyors that a major PBM required the pharmacy to collect a $35 copay for a generic allergy spray [from the consumer], then took $30 back from the pharmacy. Another said a PBM charged a $15 copay for insomnia drug Zolpidem, then took back $13.05.”

In another example, the pharmacy received only a few dollars in net payments “while patients were charged $30 above the cash price for a generic cholesterol medication,” according to a report on CNN.

In many cases, a consumer pays more to fill a prescription than the PBM paid to purchase the drug, even though consumers “assume what they are paying is the cost of the drug,” said Susan Pilch, vice president for policy and regulatory affairs with the pharmacists’ group.

The percentage of people paying more than $1,000 out-of-pocket a year for medicines also is on the rise: From 2004 to 2014, the portion of people spending more than $1,000 outside of their insurance coverage nearly tripled, from 1% to 2.8%, according to the Kaiser Family Foundation.  Kaiser also reported that 8% of adults report foregoing prescriptions because they can’t afford them.

There also is a built-in incentive in the health care industry, including the pharmaceutical sector, to set their prices artificially high.   Private insurers, PBMs, and others demand the discounts in exchange for their business.  Government entities also demand kickbacks from drug companies: States require them to pay “rebates”—basically a tax for the privilege of participating in Medicaid.

Because of these discounts and rebates to volume purchasers of their products, manufacturers of innovator drugs realized 39% of gross drug expenditures in 2015, according to a study by the Berkeley Research Group. Other players received 42% of total drug spending, with the largest share going to the various rebates, discounts, and fees that manufacturers pay to PBMs, health plans, government entities, and patients.  The total value of pharmaceutical manufacturers’ price concessions was $127 billion in 2016, according to a separate report by the Quintiles IMS Institute.

Consumers, therefore, are impacted in at least two ways.  Few of these discounts actually reach them directly, and many are required to pay their share of their prescription drug bills based upon the retail price of the drug.

Insurance companies generally create complex “drug formularies” in which their insured patients pay less for “preferred” drugs, especially generics, but can pay much more for expensive brand and specialty drugs.  Consumers may be required to pay a percentage of the cost—called co-insurance. Others may pay a flat co-payment.

The sickest patients needing newer and more expensive drugs to treat their illness may face hundreds or even thousands of dollars in out-of-pocket costs to get their medicines, especially

if the drug they need is not on their insurers “preferred” formulary list.

Patients who need generics—older drugs which are generally much less expensive—may face lower drug costs.  But if patients need a newer, brand-name drug, they could face much steeper prices.  Many patients are being asked to pay a greater share of prescription costs for more-expensive specialty drugs because of high coinsurance amounts.

More than half of out-of-pocket spending for brand-name innovator medicines by commercially insured patients is based on the full list price of the drug, according to an analysis by Amundsen Consulting.

Adding another layer of cost-exposure, a growing number of consumers face hefty annual deductibles with their health insurance policies.  In 2016, 83% of people who get health insurance at work faced a deductible for single coverage averaging $1,478.   That means a worker must spend the first $1,478 out of pocket before health insurance kicks in.  And if he or she needs medicine, the full retail price must be paid up front at the pharmacy.  Consumers who have coverage through the ObamaCare exchanges face annual deductibles ranging from $6,000 for an individual to more than $12,000 for a family.

Consumers benefit little if at all from the huge system of discounts and rebates in the pharmaceutical pricing chain.

PBMs and health plans argue that the savings they receive from the discounts and rebates the drug companies provide help reduce the overall cost of premiums.  Some portion may be shared directly with consumers through lower premiums and by helping to lower the cost of physician or hospital care. But the higher visible costs of prescription drugs are a key reason consumers are angry about drug costs.  That strategy isn’t helping them.

Some companies are trying to address the problem in other ways.

  • Express Scripts has created Inside Rx, a new subsidiary to pass discounts to patients who are uninsured or who face unaffordable out-of-pocket costs for diabetes, asthma, and other prescription drugs. Inside Rx says it delivers average savings of 34% off a drug’s typical cash price.  Patients can apply for a discount card that can be used at any of 40,000 pharmacies across the country.
  • UPMC Health Plan is working to change the way it pays for drugs, creating a new Center for Value-Based Purchasing of Pharmaceuticals, saying it wants to “fundamentally change the way medications are paid for in the U.S.” It plans to test various payment models, including payment for outcomes. This is a system that the pharmaceutical industry is also advocating.
  • CVS Health, a PBM run by the drug chain, also has developed a program to help reduce the costs of drugs at the point of sale. While nearly 9 out of 10 drugs dispensed in the U.S. today are generics, patients needing newer, often more-expensive innovator drugs may face significant out-of-pocket costs for the reasons explained above. CVS Health reports it has “developed the capability to reduce members’ [out-of-pocket] spending by applying rebates at the point of sale.”  The plan is being implemented for CVS employees and by some CVS Health clients.
  • Prescription drug companies also provide billions of dollars in donations to help those in need with the cost of their medicines.  Pharmaceutical manufacturers contributed $6.5 billion in 2014 to charities that offset the costs of medicines for patients who need assistance.  These patient assistance programs actually account for 10 of the largest 15 charities in the U.S., according to an analysis by Sanford C. Bernstein & Company.Critics say that the drug companies do this to pay a patient’s cost so they can take advantage of the added costs the insurers will pay. But doctors say the assistance is vital to their patients needing the drugs.

The Amundsen Consulting study found that prescriptions subject to a deductible or facing undiscounted prices were more than twice as likely to be abandoned at the pharmacy than those whose costs were manageable, leading to avoidable hospitalizations and poorer health outcomes.

“While biopharmaceutical companies set the list prices for their medicines, it is the health plan that ultimately determines how much a patient pays out-of-pocket,” said Stephen J. Ubl, president and chief executive officer of the Pharmaceutical Research and Manufacturers of America, or PhRMA, which commissioned the analysis.

There are a number of other price distortions in the health sector, including 340B discounts that many hospitals and clinics receive. The program began in 1992 to provide safety-net hospitals, clinics, and other providers the same kind of relief from high drug costs that Congress provided to the Medicaid program with the Medicaid rebate law.

While originally designed to help entities that serve the nation’s most vulnerable patient populations to stretch dollars further, the number of 340B entities has soared and now includes most major hospitals and many specialty medical practices, such as oncology clinics.  While 340B discounts affected 3% of purchased drugs in 2004, the discounts impacted more than a quarter of prescription drugs in 2013.

Too often, the steep discounts that these 340B entities receive are not passed along to consumers, keeping their prices high while the hospital or other facility reaps the benefits of the lowest-price the drug companies are required to accept. Some 340B providers may sell 340B drugs to non-qualified patients (usually those covered by an insurance plan) and pocket the difference, according to a study by the American Action Forum.

The Medicare prescription drug benefit program can be a model for a more transparent insurance system.  Under Medicare Part D, insurers compete fiercely for senior’s business, with plans offering transparency on the price of drugs and the drugs listed on their formularies.  And the plans have an incentive to pass the savings on to consumers to encourage them to enroll in their plans.

Pacific Research Institute economist Wayne Winegarden explains that “the current pricing model for pharmaceuticals is overly-complicated and diminishes the beneficial role that prices typically play in a market economy.”  He explains that “most rebates are not passed on to patients, and since co-pays are based on the list price, individuals’ co-pays are higher than they should be.”

Pricing reforms that establish a simpler, more transparent pricing structure are needed. The Institute for Policy Innovation published a paper on “Selective Transparency: Transparency Efforts Obscure Real Health Care Pricing Issues” by Merrill Matthews and Peter Pitts.  They detail five ways to lower prices and increase transparency.

  • Fire the MiddlemenBloomberg News, for example, reports that Caterpillar moved away from its PBM, suspecting that a quarter of the manufacturer’s $150 million annual drug bill was being wasted. The company began negotiating its own drug discounts and deals with pharmacies.
  • Promote Transparent PBMs. Bloomberg also reports that some companies are switching to “transparent PBMs” that charge flat fees for negotiating drug discounts. And some states are embracing a “fiduciary standard,” requiring PBMs to put their clients’ interests ahead of the company’s interests.
  • Reduce Regulatory Burdens. President Trump has made it a key part of his presidency to reduce onerous regulations. Food and Drug Administration Commissioner Scott Gottlieb is well aware of the agency’s regulatory roadblocks and is working aggressively to modernize the drug and device approval system.
  • Allow New Payment Models. Several experts have proposed new payment models that should be considered. For example, the pharmaceutical manufacturers are developing value-based payment approaches for some of their most expensive branded drugs, where the price of the drug depends on how successful it is.
  • Critical Care Life Insurance. This is traditional term life insurance, but it allows policyholders facing high medical costs the ability to draw on part or all of the value of the policy to pay for medical expenses. It’s not a loan; the face value of the policy is reduced accordingly. But it is a way to have both life insurance and a safety net in case the policyholder has a major medical incident. Both approaches mean fewer laws and regulations that bottleneck the health care system and make transparency so difficult. And they try to increase competition and put the consumer in charge once again.

Prescription drug pricing is teed up to be the next major health reform debate once Congress completes work on legislation to stabilize health insurance markets.

Sorting through this maze of pricing distortions in the pharmaceutical sector is important to achieve viable policy solutions rather than easy talking-point “wins” that are unlikely to succeed.

The basic truth is that billions of dollars are sloshing around in the prescription drug purchasing chain, but too few of the discounts trickle down to consumers paying out of pocket for their prescription medicines.  List prices also are artificially inflated by the bizarre pricing system for pharmaceuticals. A patient needing a drug costing $800 may have to pay half or more of the cost, but a patient needing a prescription for a generic drug may pay only a small copayment. And a patient without insurance pays the full, sometimes inflated retail price at the pharmacy.

Fueling the problem, prices for brand-name pharmaceuticals have increased as new specialty drugs have been introduced at high costs, often due to years of investment in research, the costs of manufacturing more complex medicines, and regulatory delays in getting new drugs to market.

Greater price transparency is will be a crucial element in a long-term solution to engage millions of consumers in getting the best value for their health care dollar.

– Grace-Marie Turner is the president of the Galen Institute, a non-profit research organization focusing on patient-centered health reform.


Experimental gene-silencing drug from Alnylam and Sanofi shows strong results in hemophilia

Alnylam CEO John Maraganore aims to compete with what is expected to be a blockbuster hemophilia drug from Roche.


n experimental hemophilia drug developed by Alnylam Pharmaceuticals continues to staunch bleeding in patients followed for almost one year in an ongoing, mid-stage clinical trial, the company reported Monday.

The promising results could intensify an already heated competition to develop novel treatments for the inherited bleeding disorder. The Alnylam drug, developed in partnership with Sanofi, uses a technology called RNAi to shut down dysfunctional genes. It’s a promising approach that’s attracted billions in research dollars, but hasn’t yet been used in an actual drug approved for sale.

The company says the new data support its recent decision to advance its RNAi hemophilia drug —  known as fitusiran —  into phase 3 clinical trials. If it succeeds, the drug could potentially compete against an expected blockbuster hemophilia drug from Roche.

In the current study, 33 patients have been injected once a month with fitusiran. The results so far: 48 percent have not bled after a median observation period of 11 months, according to data reported Monday at the International Society of Thrombosis and Haemostasis Congress in Berlin. Some patients in the study have been followed for up to 20 months.

Before starting the study, patients were reporting a median of 20 bleeding events per year. That number was reduced to 1 following the fitusarin injections.

The patients have two types of the disease, hemophilia A and B. Fourteen of the patients have inhibitors —  immune system antibodies that interfere with clotting factors commonly used to treat hemophilia. Patients with inhibitors are the hardest to treat effectively.

For this group, the median annualized bleed rate fell from 38 to zero, although the median observation period was shorter at six months.

Sixty-four percent of the inhibitor patients have not bled since starting treatment with fitusiran.

“These are really encouraging numbers,” said Alnylam Chief Medical Officer Pushtal Garg, in a phone interview from Berlin on Sunday. “To show annual bleed rates of one and zero is remarkable, particularly for a treatment that is administered once per month with a subcutaneous, low-volume injection.”

One third of the fitusiran-treated patients in the study reported elevated liver enzymes, a possible signal of liver toxicity, though all these patients also had hepatitis C, Alnylam said. One patient with increased liver enzymes stopped participating in the study; the rest had no symptoms and their liver enzyme issues were resolved.

There were no blood clots reported by patients in the fitusiran study. That could help the drug stand apart from Roche’s hemophilia drug emicizumab, which had a handful of serious blood clots reported in its phase 3 studies.

Roche intends to submit emicizumab for approval this year to treat hemophilia A patients with inhibitors to standard therapy. Sixty-three percent of patients receiving emicizumab reported zero treated bleeds compared with 6 percent of patients treated with bypassing agents, according to phase 3 study results previously announced. (Those results were also presented Monday at the Berlin meeting and published in the New England Journal of Medicine.)

Some analysts have projected emicizumab’s peak sales could hit $2 billion per year for patients with inhibitors, although that figure is hotly debated given the drug’s blood clotting safety issue. This leaves a potential opening for fitusiran, though its phase 3 trial won’t report data until 2019.

The Roche drug may eventually have other competition, too. Biomarin Pharmaceuticals, Spark Therapeutics, and Uniqure are all developing gene therapies to treat — and potentially cure — hemophilia.

Hemophilia drug franchises from Shire and Novo Nordisk are at risk of losing billions of dollars in sales if these new hemophilia drugs are approved. Though there are just 20,000 patients with hemophilia in the U.S., it’s a highly lucrative market.

On Sunday, Shire took the unusual step of fighting back with a preliminary injunction from a German court against Roche. Shire accused Roche of disseminating “inaccurate and misleading” information about the safety and serious adverse events that occurred in the phase 3 clinical trial of emicizumab, according to Reuters. In a statement, Roche said it stood behind the emicizumab data.

Alnylam, which is based in Cambridge, Mass., develops drugs that work through a process called RNA interference, or RNAi. All of its drugs, including fitusiran, are snippets of genetic code known as RNA that turn off genes producing disease-causing proteins. Fitusiran blocks the production of antithrombin, a protein made in the liver that prevents blood from clotting. Monthly injections of fitusiran reduce antithrombin in patients and increase corresponding levels of thrombin, another protein that promotes blood clotting.

Last October, Alnylam shares fell sharply after another of its RNAi drugs caused more deaths than a placebo in a phase 3 study. Work on that drug was halted.

But Alnylam shares have recovered this year, up 125 percent to date, on renewed investor optimism for its late-stage drug pipeline, including another RNAi drug, patisiran, targeting a rare nerve disease.

At Friday’s $84.08 close, Alnylam carries an almost $8 billion market valuation. It doesn’t yet have a drug on the market, which means investors are giving the company a lot of credit already for its late-stage RNAi pipeline, including fitusarin.


Opioid prescriptions dropped for the first time in the modern drug crisis

According to the CDC, opioid prescriptions are on the decline.

According to the CDC, opioid prescriptions are on the decline.

The number of prescriptions for opioids written by health care providers declined between 2012 and 2015, the government reported Thursday, introducing a glimmer of progress in efforts to quell the worst drug epidemic in U.S. history.

The Centers for Disease Control and Prevention said prescriptions for highly addictive painkillers such as oxycodone dropped 13.1 percent over the three-year period, from 81.2 per 100 people to 70.6.

[Opioids hospitalize nearly 23 Mainers a day]

But Anne Schuchat, the CDC’s acting director, expressed tempered optimism about the first national decline in opioid prescriptions that the CDC has reported since the crisis began in the late 1990s. She said the prescription rate is still triple the level it was in 1999 and four times as much as it is in some European countries. Even at the reduced prescribing rate, she said, enough opioids were ordered in 2015 to keep every American medicated round-the-clock for three weeks.

“It looks a little bit better, but you really have to put that in context,” Schuchat said in an interview. “We’re still seeing too many people get too much for too long.”

The overprescribing of legal opioids sparked the addiction crisis, but some addicts eventually move to cheaper or stronger drugs, especially if they run into difficulty obtaining prescription opioids. In recent years the overdose death rate from illicit drugs, such as heroin and fentanyl, has risen much faster than the rate of overdoses from medical narcotics. That means the decline in prescriptions may trigger fewer first-time addictions in the future, Schuchat said.

The improvement should be viewed “as prevention,” she said. “The fewer we get started, the fewer we get addicted to opioids.”

[The Penobscot County Jail is trying something new to fight the opioid crisis]

Gary Mendell, founder of the anti-drug advocacy group Shatterproof, noted “the improvements being made,” citing estimates that 80 percent of opioid abusers first become addicted to prescription narcotics, not street drugs. But, he said, the reduction is “not even close to what could occur in this country.”

In particular, Mendell said, prescribing practices should be measured and responded to in real time. The cumbersome CDC process of collecting data from states and counties is inefficient, he said.

“Can you imagine being on a conference call with a company and they announce data that’s two years old?” said Mendell, a former hotel executive. “There’s a simple saying in business: What doesn’t get measured doesn’t get done.”

The opioid crisis appears to have left no community untouched as it’s mushroomed into an epidemic since the turn of the century. Prescription opioids alone killed nearly 180,000 people from 2000 to 2015 and those overdoses, abuse and dependence on medical narcotics created an annual “economic burden” estimated at $78.5 billion, according to the new report.

In 2015, the latest year for which the CDC has released data, more than 33,000 people died of overdoses that involved an opioid, including more than 15,000 who had taken a prescription narcotic. Nearly 13,000 more were killed by overdoses of heroin.

State data and a nationwide survey conducted by the New York Times indicate that those figures may be rising sharply in 2016.

More than two million people are addicted to opioids, the government estimates. In 2014 alone, there were 1.27 million emergency room visits or inpatient hospital stays for opioid-related health problems, another government agency reported in June.

The critical shortage of treatment for people with opioid use disorder also has complicated plans by the President Trump and Republicans in Congress to repeal and replace the Affordable Care Act. States confronting major drug problems have resisted federal proposals to roll back Obamacare’s expansion of Medicaid, which is helping to fund treatment for many people.

[Maine’s health care providers have a chance to save lives lost to opioids. It’s time they seize it.]

There are also indications that prescriptions for opioids have been dropping since 2015. In the past year, some private-sector data collectors have reported prescription declines on par with the data in the CDC report. Customers of Cigna Health Insurance, for instance, have consumed nearly 12 percent fewer opioids in the past year, according to Will Lopez, senior medical director of Cigna Behavioral Health.

The CDC report also confirmed another critical factor in the crisis: It found wide disparities in opioid prescriptions in counties across the nation. Doctors in some counties in hard-hit parts of Appalachia, the southwest and New England prescribed the equivalent of 958 to 5,543 milligrams of morphine per capita in 2015. In other locations, prescribers authorized zero to 454 milligrams in the same year.

The report also determined, as other researchers have, that opioids are more heavily prescribed in small town America, in counties with larger white populations, and in places where unemployment and Medicaid enrollment are higher. It also found that they are prescribed more frequently in counties where arthritis and diabetes rates are higher than average.

Still, those factors only explain about a third of the variation among counties, Schuchat said. “That suggests to me that clinicians may not know what the right amount of prescribing is. They may be prescribing based on custom and tradition and what they were taught” in medical school, she said.

In the last few years, medical and public health authorities, including the CDC, have been urging doctors to cut back on the number of pills, the dose and the duration of the prescriptions they offer – a turnaround from just 15 years ago, when a nationwide movement urged physicians to more aggressively treat their patients’ pain. Even before the CDC issued guidelines last year, studies were warning prescribers of the dangers of dispensing too many opioids.

The data indicate that at least some prescribers are heeding the message. Nationally, prescribing peaked at the equivalent of 782 milligrams of morphine per person in 2010, declining to 640 milligrams per person in 2015.

The study also found a continued increase in long-term prescribing of opioids. The average length of prescriptions rose steadily from about 13 in 2006 to about 18 in 2015, the data show. But Schuchat cautioned that as fewer people are receiving short-term prescriptions, those who take opioids for years for chronic pain may have skewed the average. The CDC has said that there is no evidence that opioids are effective long-term and suggests that people with chronic pain, one of the most common reasons for visiting a health-care provider, seek alternatives.

“Improving the management of chronic pain is very important,” Schuchat said. “There are multiple approaches. Larger-scale studies suggest that opioids, even high-dose opioids, are not in the long run effective for chronic pain, and in the long run may even be dangerous.”


Post-Brexit EU drug regulation deal urged by ministers


The UK will continue to co-operate with the European Union on medicine testing after it leaves the bloc, two senior ministers have suggested.

Business Secretary Greg Clark and Health Secretary Jeremy Hunt said such a deal would be “in the interests of public health and safety”.

“The UK would like to find a way to continue to collaborate with the EU,” they wrote in a Financial Times letter.

There are fears Brexit may cause delays in UK patients getting new drugs.

Currently the London-based European Medicines Agency (EMA) authorises drugs for use across the EU, including the UK.

However, it is expected to move out of the UK after Brexit, raising uncertainty over whether the UK will need to develop its own separate drug approval system.

Industry experts have warned that if this happens pharmaceutical firms could be slower to seek permission for their drugs to be used in just one country, focusing instead on getting their drugs approved for larger, more lucrative markets.

The UK pharmaceuticals trade association has also warned that Brexit could undermine future investment, research and jobs in the country.

But speaking on the BBC’s Today programme, the UK managing director of US drugs giant Pfizer, Erik Nordkamp, said there were other issues than Brexit that the industry wanted to see addressed.

“The letter in the FT this morning is significant… because it acknowledges there are some risks that need to be addressed with regulation, with trade, but at the same time the government needs to address the long-standing issues that are there.”

Access to medicines

The ministers wrote that the UK “will look to continue to work closely with the European Medicines Agency (EMA).”

“Our overall aim is to ensure that patients in the UK and across the EU continue to be able to access the best and most innovative medicines,” they added.

In the letter, they cited examples where the UK and EU partnership had helped patients, including the licensing of 130 products to treat rare diseases.

In an attempt to reassure the industry, they also said if it wasn’t possible to arrange “our desired relationship with the EU”, then Britain would “set up a regulatory system” to process drugs licences “as quickly as possible.”

Greg ClarkImage copyrightPA
Image captionGreg Clark said the current UK and EU partnership had been beneficial

In April, EMA executive director Guido Rasi said continued co-operation was theoretically possible but it would be up to EU governments to decide whether to offer such a deal.

Pharmaceutical firms have been pushing for some kind of clarity over what the UK’s exit from the EU will mean for the industry.

Mike Thompson, chief executive of the Association of the British Pharmaceutical Industry, said the ministers’ letter was “a welcome recognition that the future of medicines regulation is a key priority for the government”.


DEA does not need warrant to subpoena Oregon prescription drug information

A three-member panel of the 9th U.S. Circuit Court of Appeals ruled Monday that the Drug Enforcement Administration does not need a court-ordered warrant to subpoena information from Oregon's Prescription Drug Monitoring Program. It also found the ACLU should not have been allowed to intervene in the case.  (Associated Press photo)

A three-member panel of the 9th U.S. Circuit Court of Appeals ruled Monday that the Drug Enforcement Administration does not need a court-ordered warrant to subpoena information from Oregon’s Prescription Drug Monitoring Program. It also found the ACLU should not have been allowed to intervene in the case. (Associated Press photo) (AP Photo)

A federal appeals panel ruled Monday that the U.S. Drug Enforcement Administration can issue a subpoena for information in an Oregon database that tracks doctors and the narcotics they prescribe without getting a court order, reversing a lower court ruling.

The three-member panel of the 9th U.S. Circuit Court of Appeals found the federal law that grants subpoena power to the agency preempts Oregon law, which requires a court order.

Congress enacted the Controlled Substances Act, in part, “to strengthen law enforcement tools against the traffic in illicit drugs” and allows federal authorities to obtain such information through a subpoena, the appeals panel noted.

State law directly conflicts with the federal statute, providing that the Oregon Health Authority disclose information from its prescription monitoring program in response to a court order based on probable cause.

Oregon’s law undermines the intent of Congress to empower the Drug Enforcement Administration, the panel ruled.

The appeals court also found that the U.S. District Court shouldn’t have allowed the American Civil Liberties Union to intervene in Oregon’s case against the DEA because it failed to establish independent standing.

U.S. District Judge Ancer L. Haggerty ruled in 2014 that patients have a reasonable expectation of privacy for their prescription records and that law enforcement officials must seek a warrant for information from Oregon’s database.

The Drug Enforcement Administration appealed.

The Oregon Legislature created the monitoring database in 2009 to log prescriptions filled by pharmacies in the state, the physicians who prescribed the narcotics and the patients who use them. The state included privacy protections, including the court order. The database went live two years later.

The Drug Enforcement Administration argued it could use administrative subpoenas under the Controlled Substances Act.

The state sued the agency after it issued three subpoenas for database information. The American Civil Liberties Union joined the case on behalf of four patients and a doctor, taking the state’s argument one step further in contending that federal agents must have probable cause and a signed search warrant for the information.

The subpoenas could violate a person’s Fourth Amendment right to privacy and unreasonable search and seizure, the ACLU argued. The ACLU sought a court injunction.

Haggerty didn’t analyze whether the ACLU had the right to intervene, and instead found that the DEA violated privacy rights asserted by the ACLU, the appeals panel’s opinion said.

“We reverse without reaching the merits of the Fourth Amendment claim,” the appeals panel said. Because the ACLU is seeking a different outcome than the state, it needed to show independent standing to intervene in the case and it did not, the panel ruled.

The DEA’s two administrative subpoenas sought records of a single patient and two prescribing physicians, not records related to the ACLU, the appeals court said.

The appeals panel said it recognized the “particularly private nature of the medical information” at issue and said the ACLU’s concern about disclosure wasn’t unreasonable. Yet even so, the ACLU lacked standing because it and those it represented weren’t “under an impending threat of disclosure.”

The appeals court did point out that the state still has the power to resist a DEA administrative subpoena, which would require the DEA to then get a court order for the information.

The appeals panel described this step as “a critical safeguard in light of the particularly important privacy interest implicated here.”

Attorney Nathan Freed Wessler, a New York-based lawyer who argued the appeal for the American Civil Liberties Union, said he was disappointed.

Next month, the ACLU will appear in federal court in Utah in a separate lawsuit and make the same argument that the DEA violates privacy rights by using “mere administrative subpoenas.”

“The court recognizes that medical records are private and sensitive and therefore require strong legal safeguards,” Wessler said. “Regrettably, it held that our clients lacked ‘standing’ to press for those safeguards in this litigation.”