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Sandeep Singh Dhillon
MSD Malaysia launches dual-mechanism drug that significantly lowers LDL-C levels – MIMS Malaysia
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MSD Malaysia has recently announced the approval of ATOZET, a combination of ezetimibe and atorvastatin in Malaysia, on 26 July – at a media launch, held at Ruyi & Lyn, Bangsar, KL. The event was graced by consultant cardiologists, Dr Jeyamalar Rajadurai and Dr David Quek, who shared further insights into the prevalence of hypercholesterolemia, disease complications and advisory on hypercholesterolemia management.

The once-daily combination tablet boasts a dual mechanism of action, treating two main sources of cholesterol in the blood. Ezetimibe inhibits the absorption of cholesterol in the digestive tract, while atorvastatin inhibits the production of cholesterol in the liver. ATOZET is indicated to reduce the risk of cardiovascular events in patients with coronary heart disease (CHD) and a history of acute coronary syndrome (ACS), either previously treated with statin or not.

It is also indicated as an adjunctive therapy to diet for use in adults with primary (heterozygous familial and non-familial) and homozygous familial hypercholesterolemia or mixed hyperlipidaemia in patients not appropriately controlled with a statin alone, or already treated with a statin and ezetimibe.

“Heart disease has been the main cause of death in both men and women. In addition, it is two and a half times more common than all cancers combined for more than a decade. It is a very important cause of premature mortality in both and women below the age of 70. And, one important cause of cardiovascular disease is high cholesterol,” shared Dr Jeyamalar.

High levels of hypercholesterolemia within the Malaysian population

According to the National Health & Morbidity Survey 2015, the overall prevalence of hypercholesterolemia – both known and undiagnosed – among young adults aged 18 years and above in Malaysia was 47.7%. There was a general increasing trend with age: from 22.0% in the 18 – 19 years age group, reaching a peak of 68.8% among the 55 – 59 years age group.

“From above 30 years, there is a huge jump in the prevalence of hypercholesterolemia. In fact, in a survey that was done among 13-year-old students… it was discovered that 23% of these students had high cholesterol levels. We are talking about one in four 13-year-olds with cholesterol levels of more than 5.2mmol,” she explained, depicting the dire situation of heart health in Malaysia.

A REALITY Asia study which examined treatment patterns, goal attainment and factors influencing treatment among patients in six Asian countries who were taking statins, also saw more than half of the participants (particularly in patients at highest risk of various cardiovascular disease, including those with CHD or diabetes) did not accomplish the recommended levels of LDL-C.

Reducing LDL-C levels by 27%

There is evidence suggesting that lower LDL-C levels are associated with fewer CV events: the greater the LDL-C reduction, the greater the CV risk reduction. These benefits related to LDL-C reduction are not specific to statin therapy. Therefore, it seems appropriate to reduce LDL-C as low as possible, at least in patients with very high CV risk,” elaborated Dr David Quek.

ATOZET has been shown in multiple studies to effectively lower LDL-C levels. In a 6-week, multicentre, double-blind, randomised, parallel-group study, ATOZET was shown to provide significantly greater LDL-C reduction (27%) in 196 patients with hypercholesterolemia – compared to doubling the dose of atorvastatin alone.

Additionally, the IMPROVE-IT study which evaluated the clinical benefit of ezetimibe/simvastatin combination compared to the simvastatin alone, has revealed that the combination provided incremental benefits in reducing the many cardiovascular-related risk factors in 18,144 acute coronary syndrome (ACS) patients ̶ a relative risk reduction of 6.4%.

“With the launch of ATOZET, we hope this will enable healthcare professionals to think beyond statin monotherapy when treating patients struggling to achieve their cholesterol level goals. The combination of ezetimibe and atorvastatin in ATOZET represents a new breakthrough, which MSD hopes will aid in addressing the critical unmet needs of patients in Malaysia,” expressed Chris Tan, Managing Director and Zone Leader for Malaysia, Singapore and Brunei at the official launch of ATOZET. MIMS

Sandeep Singh Dhillon
UN: “Scales have tipped” as more HIV-infected individuals get drugs, halving AIDS-related deaths – MIMS Malaysia
Pharma Notables
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Brenda Lau

More than half of all HIV-infected individuals are on drugs to treat the virus for the first time in the four-decade global AIDS epidemic, the United Nations said in an official report on 20 July. AIDS deaths are also almost halved of what they were in 2005, based on estimates.

Experts worldwide applauded the progress, but questioned if the billions spent in fighting the epidemic for the past two decades should have produced more impressive results.

“When you think about the money that’s been spent on AIDS, it could have been better,” expressed Sophie Harman, a senior lecturer in global health politics at Queen Mary University in London.

More resources seem to have been channelled to strengthening health systems in poor countries, she added.

“The real test will come in five to 10 years once the funding goes down,” Harman said, warning that some countries might not have the funds to sustain the U.N.-funded AIDS programmes on their own.

Worsening the problem, the Trump administration has also proposed a 31% cut in contributions to the U.N. starting this October.

UN report points towards positive outcomes

The report states that approximately 19.5 million HIV-infected individuals were taking AIDS drugs in 2016, compared to 17.1 million in 2015. According to UNAIDS, there were about 36.7 million HIV-infected individuals in 2016, up slightly from 36.1 million the year before.

Michel Sidibe, UNAIDS’ executive director said that more countries are starting treatment as early as possible, proving right the scientific findings of the approach ̶ keeping people healthy and preventing new infections.

Many studies also show that those whose infections are under control, are far less likely to pass it on to an uninfected sex partner.

“Our quest to end AIDS has only just begun,” he wrote.

The report also noted that about three-quarters of HIV-infected pregnant women now have access to medicines that prevent the virus from being transmitted to their babies. Five hard-hit African nations also now provide lifelong drugs to 95% of pregnant and breast-feeding women with the virus.

The death toll from the disease has also dropped dramatically in recent years as the drugs are now more affordable and accessible, making the illness a manageable disease.

AIDS unlikely to be eliminated forever

But Harman said that the report was unrealistic.

“I can see why they do it, because it’s bold and no one would ever disagree with the idea of ending AIDS. But I think we should be pragmatic,” she remarked. “I don’t think we will ever eliminate AIDS; so it’s possible this will give people the wrong idea,” she added.

Elsewhere, the World Health Organisation (WHO) unintentionally supported Harman’s statement, warning that there are rising levels of resistance to HIV drugs. This could undermine promising progress against the AIDS epidemic, if effective action is not taken early.

Six out of 11 countries surveyed in Africa, Asia and Latin America observed more than 10% of HIV patients on antiretroviral drugs, already have a strain resistant to most widely-used medicines.

Upon reaching the 10% threshold, the WHO recommends countries to urgently review their HIV treatment programmes and switch to different drug regimens to limit the spread of resistance.

Hope still remains in cows

All hope is not lost as researchers from the International AIDS Vaccine Initiative (IAVI ) and the Scripps Research Institute have discovered that special types of antibodies produced by cows, can neutralise HIV. This could mean a vaccine in the future.

The cow’s antibodies, which would normally take humans three to five years to develop, were produced by the cow’s immune system in a matter of weeks. It also showed that it could neutralise 20% of HIV strains within 42 days. By 381 days, 96% of strains were neutralised in lab tests.

“Unlike human antibodies, cattle antibodies are more likely to bear unique features and gain an edge over HIV, said Dr Dennis Burton, part of the research team.

Creating a vaccine out of cow antibodies still remains a significant challenge – but the team says that the cattle study could help point the way. MIMS

Sandeep Singh Dhillon
When The Drug You Need Doesn’t Make Money – Forbes
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By Alison Bateman-House, CONTRIBUTOR

What if a drug you need doesn’t earn enough money for the company to continue making it? In thinking about this, let’s start with a hypothetical. Unfortunately, you cannot eat protein or gluten–no matter what form they are in, if you consume either, you become violently ill. So you have learned to eat a gluten- and protein-free diet (for the sake of our hypothetical, let’s not worry about whether this is in fact possible). You’ve tried everything you can find at the grocery store, online or made from scratch, and the food that best keeps you healthy and functioning is a vegan “PowerBar” made by the food company VeganDelite. You eat them at least five times a day, but apparently there aren’t many other fans, because VeganDelite announces that it will stop making its PowerBars. You call to protest this decision, only to have the customer service representative say he’s sorry that the company won’t be making your favorite product any more, but there are other vegan PowerBars on the market and surely you’ll like one of them. You protest, explaining you’ve tried everything else, but VeganDelite’s version is what works best for you. This isn’t a mere matter of preference: your health and well-being are at stake. The man apologizes but says he just isn’t able to help you: it was a corporate decision and made due to insufficient sales in the face of alternative substitutes. So you go online and start a petition, but it doesn’t get much attention or traction. You call your local news channel and your congressional representative, but nobody seems willing to join you in calling for VeganDelite to change its decision and continue manufacturing a product for which there is apparently little demand except for you.

Now let’s drop the hypothetical. The parents of one-year-old Christian Mumm are calling on pharmaceutical company GlaxoSmithKline (GSK) to make available its anti-seizure medication Potiga. However, GSK stopped selling the drug at the end of June. The company reports that “as few as 1,500 patients with epilepsy are treated with this medicine globally, with numbers continuing to decline.” 1,500 patients around the world is akin to VeganDelite making its PowerBars just for you. But while you were unable to stir much sympathy for your cause, Mumm’s hometown held a rally in support of the family’s quest to keep their son on Potiga. An online petition was started, gaining over 2,300 signatures in its first three days. Congressman John Larson has weighed in, stating, “It just is so disturbing to me that there is a solution here and all that it requires is a company to say yes, they will make available this successful drug that helps this child out.”

Potiga isn’t the only anti-seizure medicine on the market: indeed, it is apparently only used by a handful of patients. But Mumm’s doctors have tried around seven other medications and found Potiga best at preventing his seizures while preventing debilitating side effects. So Mumm and his family have good reason to desire the drug to continue being available, but GSK also has good reason to stop manufacturing and selling the product.

Is it appropriate or reasonable to demand a company to continue making a product when it does not want to? Does it matter that in one case the desired item is a drug and in the other a food? Does it matter than in one the person who needs the item is a child and in the other it isn’t?

Comparing these real and hypothetical cases highlights several issues. First, we think drugs are somehow different from other goods, even goods as vital as food. I think this is because we view drugs as inherently tied up to issues of life, death and health, even more so than our hypothetical medically necessary food bar.

Also, we tend to want to help identified victims, particularly so-called “innocent victims,” whose suffering is in no way self-inflicted due to lifestyle or behavioral choices. Our hearts ache for little Christian Mumm, who has gone through so much in his one year of life, and for his family, who must be aghast that the drug that has helped their little boy won’t be available anymore­—not even because it has been found to have additional or worse side effects, but because of a market decision. We know, as background knowledge, that both in our country and globally there are innumerable people who are unable to access the drugs they need. But it is hard to grapple with that vast problem of unnamed people, whereas a story of a Connecticut child is much easier to identify with and to feel morally engaged by.

Third, we tend to think of pharmaceutical giants as faceless, deep-pocketed entities for whom it would be no trouble at all to keep manufacturing a drug. We don’t think about the fact that the manufacturing facility being used to produce Potiga could be used to produce a more utilized drug that lots of patients could benefit from. Instead, we seem to think multinational pharmaceuticals have unlimited resources of people, manufacturing capability, raw ingredients and all the other things needs to produce, for an indefinite period of time, a drug.

Finally, this case points out that in some cases the free market leads to results we find uncomfortable, disturbing or even morally untenable. GSK has no market incentive to produce a drug that it sells to only 1,500 people. When it comes to drug development for rare diseases, where perhaps 1,500 people globally constitutes the entire population of patients with a certain condition, companies have made it worth their while to discover and develop drugs because they are sold at astronomical prices. Because there are no other treatments, insurance companies and governments will purchase those incredible expensive drugs. But in the case of epilepsy, where other treatments beside Potiga are available, GSK would not be able to say, OK, we will continue making the drug but we must raise its price exponentially to be able to justify our ongoing investment.

That the market sometimes seems to fail us ought not be a surprise. After all, campaigners for those diseases that occur primarily in the less wealthy regions of the world have been making this argument for years. If a drug, vaccine or device can be made but those who would purchase it are not capable of paying the prices necessary for the developer to make a profit, what do we do? Do we expect philanthropic agencies to leap into the breach, as the Gates Foundation has done with the quest for a malaria vaccine? Do we say to companies that, as a price of doing business (and, in the case of GSK, quite profitably), they must also make and distribute drugs like Potiga that will likely lose money but help a small number of patients? Do we demand GSK surrender its rights to Potiga to a government or foundation that might be able to make the drug? Do we set aside money to fund such drug production?

These are weighty issues that will not be solved quickly. In the meantime, GSK ought to scour its inventory to see if there is extra Potiga that can be made available to Christian Mumm and any other patients in his situation. The energy being spent to rally and sign petitions ought be diverted to asking stakeholders in this issue–government, business and philanthropic–to resolve this ongoing issue. For the congressman who says the solution is just for GSK “to say yes,” what are you going to do to persuade the company to say yes? Is there political will to force business to manufacture and provide non-profitable but needed drugs? If not, what solution is preferable, and who will be responsible for enforcing it? Not only a one-year-old in Connecticut, but people around the world are waiting impatiently for the answer. Up until now, we’ve kicked the can down the road. When are we going to actually deal with this issue?

Read the full article here

Sandeep Singh Dhillon
How Not To Lower Healthcare Costs – Forbes
Pharma Notables

By Robert Pearl, M.D.,

Citing recent estimates that nearly one-third of clinical laboratory tests are unnecessary for patients, University of Pennsylvania researchers posed a question with huge cost-savings potential: What would happen if doctors were able to look at the price of these tests before ordering them?

To determine whether price transparency might change the way physicians behave, the researchers spent a year studying how frequently clinicians ordered 60 different lab tests at three Philadelphia hospitals. They randomly assigned half of the tests to a control group with no prices posted and the other half to an intervention group for which the “Medicare allowable fees” (the maximum amount Medicare will reimburse) were displayed in the electronic health record system for all clinicians to see.

The results, published in a recent issue of JAMA Internal Medicine, show that making doctors aware of lab-test pricing has almost no influence over medical decision-making. Surprised? You shouldn’t be.

Healthcare Costs In Context

With national healthcare expenditures topping $3.2 trillion annually, legislators on Capitol Hill are looking to root out the kind of wasteful spending that has flattened American wages and sent health insurance premiums soaring. At the same time, Congress is under pressure from voters not to sacrifice the quality or accessibility of medical care.

What few seem to realize, however, is that financial disincentives in healthcare rarely work and, more often, carry unintended consequences. To understand why, consider a daycare experiment carried out by economists and made famous by Freakanomics.

Several years ago, administrators at a childcare facility were asked to collect a modest late fee from parents who picked up their kids more than 10 minutes after the normal closing time.

The idea behind the experiment was to reduce the after-hours burden on caregivers. The result was quite the opposite.

Prior to implementing the late fee, parents did their best to arrive on time, not wanting to inconvenience the people caring for their kids. But when the daycare centers began assigning a fee, the parental perspective shifted. Lateness was no longer seen as an imposition on the workers but rather as a service that could be bought. Parents viewed it as simply the going rate for completing an urgent project or running an errand after work. And because the consequences had gone from personal to transactional, tardiness at the daycare centers doubled.

For physicians, medicine is much more personal than transactional. Doctors worry about whether their patients can afford healthcare coverage and, as a result, ask themselves whether a test or procedure will help. But in the context of deciding whether to order a test that adds $10 to $15 to a hospital bill, the savings hardly seem worth it.

Besides, residents who fear being grilled by an attending physician for not having the most recent laboratory information handy no doubt see the added expense as a small price to pay. And, of course, clinicians know that patients rarely pay the added cost themselves. These contextual clues are important to consider when thinking about how best to lower costs in American hospitals.

So, What Approaches Would Work?

In my experience with leading doctors, I have observed three approaches that have proven effective in modifying physician behavior.

1. Inspire healthy competition. When it comes to their performance, doctors are highly competitive. They like being perceived as “the best” among their peers–a point of pride ingrained in physicians throughout their training. Therefore, presenting doctors with unblinded performance data has the power to modify their behavior. For example, showing which doctors are “best” at achieving high-quality and cost-efficient outcomes would inspire all physicians to learn from, and compete with, the top performers.

I have seen this competitive spirit in action when comparing lengths of stay among hospitalized patients at different Kaiser Permanente medical centers. By measuring outcomes, we know that some physicians are better at helping their patients improve faster and get home sooner. When confronted with this data, the physicians who lagged their peers most often made the necessary adjustments to improve.

2. Appeal to the heart. Physicians usually know when expenditures add little value and they care about the cost impact on their patients. Therefore, the second opportunity to shift behavior is to reframe the problem in human terms, with a focus on the patient, not the dollars.

Devi Shetty, a successful cardiovascular surgeon in India, communicates the hospital’s P&L to all physicians and hospital staff each day. But he doesn’t quantify the bottom-line impact in terms of rupees; instead, he translates it into the number of free surgeries the facility can perform the next day. By showing everyone from housekeepers to department chiefs how a dollar saved can improve a patient’s life, Dr. Shetty’s entire staff strives to lower costs.

3. Make the right thing the easiest thing to do. According to the Penn study, “91% of resident physicians reported that unnecessary lab testing was due to the habit of entering repeat daily lab test orders on the patient’s first day of admission.” Doctors who place these “routine standing orders” at the outset of a patient’s stay rarely discontinue the lab studies even after a patient is stable.

That’s why, except for certain life-and-death situations, it would make more sense for doctors to order these tests one day at a time. Requiring them to do so would make it easier for doctors to consider whether the test is necessary.

The Power Of Perception

Perception in healthcare–what doctors see, hear and feel–is often as powerful as logic. Usually, changing perception in healthcare requires a change in context, not a change in logic.

For example, emailing doctors a warning about unnecessary laboratory testing or requiring them to attend a lecture on the rising cost of medical care won’t change their actions. Do as the researchers did–simply post lab-test prices–and doctors will see it as little more than administrative interference.

These approaches fail to produce the predicted or desired outcomes in healthcare because they ignore what truly motivates physician behavior.

By revealing how the best clinicians are achieving high-quality and cost-efficient results, more doctors will make the effort to improve. By helping doctors connect the dollars they save with the mission-driven outcomes they want, more physicians will do the right thing. And by making it easier for physicians to reconsider the patient’s clinical status each day, the number of wasteful laboratory tests will decline.

Money can have a major impact on physician perception and behavior. But we should remember that using money as motivational tactic alone will, as often as not, produce unintended and undesirable results.

Dr. Robert Pearl is the author of “Mistreated: Why We Think We’re Getting Good Health Care- And Why We’re Usually Wrong” and a Stanford University professor. Follow him: @RobertPearlMD.

Sandeep Singh Dhillon
Did You Grow Up Thinking You’re Allergic To Penicillin? Guess Again – Forbes
Pharma Extra, Pharma Notables

By Rita Rubin

For years, whenever a health-care provider asked whether you were allergic to any medications, you might have dutifully noted yes, penicillin, which happens to be the most common drug allergy of all. You might not remember ever having an allergic reaction to penicillin, but that’s what your parents always told you, and they wouldn’t steer you wrong.

Well, a couple of new studies suggest that unless your symptoms were pretty dramatic, you might not be allergic to penicillin after all. Researchers tested children and adults who’d been labelled as allergic to penicillin but whose symptoms were relatively mild and found that most tolerated the drug just fine.

Why should you care whether you or your children are allergic to penicillin?

While penicillin is the oldest antibiotic, it and other members of the penicillin family, such as amoxicillin, are still effective, first-choice treatments for a wide range of bacterial infections. But once people are labelled as allergic to penicillin–previous studies suggest that 5% to 20% of the population has been deemed allergic to the drug– doctors instead prescribe second-choice, broader-spectrum antibiotics, which, in the case of garden-variety bacterial ear infections, is kind of like swatting a fly with a sledgehammer.

Broad-spectrum antibiotics kill beneficial bacteria as well as the bad actors, increasing the risk of side effects such as diarrhoea and the possibility that some microbes will develop antibiotic resistance. On top of that, those broad-spectrum antibiotics cost a lot more than generic penicillin or amoxicillin.

In a study published online Monday by the journal Pediatrics, researchers enlisted the help of parents of children ages 4 to 18 who were seen in the emergency department at Children’s Hospital of Wisconsin. The scientists asked 605 parents who reported that their children were allergic to penicillin if they would complete an allergy questionnaire.

Questions included the age of the child when diagnosed with a penicillin allergy, why the drug was prescribed, symptoms of an allergic reaction, how long after the first dose it occurred and whether a parent, doctor or both diagnosed the allergy. The questionnaire also listed 17 symptoms, ranging from a rash to throat swelling and asked the parents to check the ones that occurred in their child after taking penicillin.

Before administering the questionnaire, the researchers consulted with a pediatric allergist about which symptoms were “high risk,” or likely the result of an allergic reaction, or “low risk,” or likely not due to an allergic reaction. High risk symptoms included facial, lip or throat swelling, while low risk symptoms included a rash, itching or hives.

Of the 597 children whose parents completed the questionnaire, nearly three-fourths had low-risk symptoms. The researchers had enough funding to offer testing for penicillin allergy to the parents of 100 low-risk children whose symptoms had been confirmed by their primary physician. The testing consisted of the standard three-tier process: administering penicillin first by a skin prick (also called scratch) test, then by injection and then orally.

“We are prepared to handle serious reactions if one were to occur,” lead author Dr. David Vyles explained to me.

But it turned out that none of the 100 children tested were found to be allergic. In other words, the questionnaire did a good job of identifying the children who really weren’t allergic to penicillin. But, Vyles said, much bigger studies are needed before the questionnaire alone could be used to identify patients labeled as allergic who could safely take penicillin.

In a related study published in April in the journal Emergency Medicine Australasia, researchers in Sydney performed the three-tier allergy test on 100 adult emergency department patients who reported a penicillin allergy. The Australian scientists did not first screen the patients to determine whether their allergy symptoms were high risk or low risk, but they did exclude those who had previously experienced anaphylaxis, a severe, life-threatening allergic reaction, after taking penicillin. Of the 100 patients tested, the researchers found that 81 weren’t actually allergic to penicillin.

“It would be great to examine whether a combination of risk assessment and oral challenge alone could ‘de-label’ the majority of reported penicillin allergies in children.” emergency department physician Dr. Joseph Marwood, lead author of the Australian study, told me in an email. “If this could be demonstrated as safe, without labor-intensive and uncomfortable skin prick testing, it could quickly become practice in the pediatric ER and help children receive the most appropriate antibiotic for their initial illness and beyond.”

Why would people think they’re allergic to penicillin when they’re not?

Vyles thinks parents and even physicians are sometimes too eager to blame penicillin for symptoms that actually are related to the underlying illness. In his study, the children’s primary care doctors had witnessed the supposed allergic reaction in only 14 of the 100 who were tested. In the majority of cases, the primary care doctors diagnosed a penicillin allergy based on what the parents told them.

Personal experience spurred Vyles, an assistant professor of pediatrics at the Medical College of Wisconsin in Milwaukee, to investigate the question.

When his now 9-year-old son was 2, he developed a rash after taking amoxicillin. Because of the rash, the boy’s pediatrician concluded he was allergic to penicillin.

The next time Vyles’ son had an ear infection, his doctor prescribed a broad-spectrum antibiotic instead of amoxicillin. Vyles says he would have had to pay more than $100 more out-of-pocket for the brand-name broad-spectrum antibiotic than for generic amoxicillin.

So he did what only a physician parent could do: He got amoxicillin instead and “challenged” his son with a dose to see if he had any kind of a reaction. Nada. Same thing happened with his daughter, now three. She developed a rash four days after she began taking amoxicillin, so her pediatrician labeled her as allergic to penicillin drugs. Vyles, by then highly skeptical, gave her a dose of amoxicillin, and she did fine.

Again, do not try this at home, but you might want to see an allergist. Says Vyles, “Anybody who has penicillin allergy and questions it should go through the testing.”

Sandeep Singh Dhillon
FDA list of Drugs without Generic Competition to Prevent Price Gouging – 2017 Business Insider
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By Lydia Ramsey

The FDA just took a step that could increase competition and prevent price gouging on drugs that seemingly jump in price overnight.

In May, Food and Drug Administration commissioner Dr. Scott Gottlieb said he wanted to make it more difficult for drugs that are off patent to jack up the price of the medication because they don’t face any competition. The biggest example of this was Daraprim, a decades-old drug that then-Turing CEO Martin Shkreli increased in price from $13.50 to $750 a pill.

To keep that from happening in the future, the FDA on Tuesday published a list of more than 200 drugs that have fallen off patent where the FDA hasn’t received any applications for a generic drug version of that drug.

Before now, it wasn’t too clear which drugs had generic alternatives and which didn’t. That left room for drug companies to buy up those drugs without people noticing and quietly raise their prices. The list could help keep a closer eye on the pool of drugs without generic competition. Ideally, other companies could make generic alternatives to increase competion, lower prices, and keep the drugs from becoming the target of price hikes.

“No patient should be priced out of the medicines they need, we must do our part to help patients get access to the treatments they require,” Gottlieb said in a tweet. “Competition and access are foundational elements to continued pharmaceutical innovation, public health improvement,” he said in a follow-up tweet.

The list includes everything from simple chemical compounds to antibiotics, and glucagon hydrochloride, an emergency diabetes drug that raises the level of blood sugar when it falls too low.

Here is the list

Sandeep Singh Dhillon
What Would Steve Jobs Tell The Pharma/Biotech Industry? – Bioprocess Online
Pharma Extra, Pharma Notables

By Martin Lush, Global VP, NSF Health Sciences

Whether you’re a fan of Steve Jobs and his products or not, two things are undeniable: He was very successful and very different. Now you can relax; this short article will not provide a blow-by-blow account of the man and his methods. “What would Steve Jobs tell the pharma/biotech industry?” is just a metaphor to encourage our industry to radically change — not by reinventing the wheel, but by copying the success of others.

Why Maintaining The Status Quo Is No Longer Good Enough

Please take a look at my last article, “Brexit, Trump, What Next? 6 Rules to Succeed in an Era of ‘Brutal Disruption”, for a reminder of the challenges and opportunities facing the pharma/biotech industry. This article reaffirms the sentiments of the great Albert Einstein:
“The definition of insanity is doing the same thing over and over again, but expecting different results.”
We live in an era of “new” everything — new science, new regulations, new presidents, new governments, and new challenges. To prosper in this era of brutal disruption, we have to think differently.
Like some of you, I have read a lot about Jobs and his methods, and what made Apple so successful.1-4 In writing this article, I simply imagined asking Jobs the question: “Based on your experience, successes, and failures, what would you tell the pharma/biotech industry?” Since he was a man who liked to get straight to the point, I’ve kept my imagined list of his recommendations to just five.
Steve’s Top Five Recommendations
1. Simplification Is Survival
Jobs was a complex man driven by a simple belief: Simplification is survival. For the pharma/biotech industry, this means drastically simplifying everything. Let’s start with the simple stuff first.
Your call to action:
Simplify documentation systems, particularly SOPs. For many companies, SOPs are out of control. They have become overly complex and impossible to follow. Instead of improving consistency, they increase the risk of errors and mistakes. Instead of being written for the user, they have been written for the auditor or regulator. This must stop. If you want guidance on how to write a good SOP, just look at a recipe book! You’ll see lots of pictures and simple diagrams! So, the answer to better documentation systems is in your kitchen.
Simplify batch manufacturing records (BMRs). Excessively detailed instructions, poorly designed documents, and excessive check signatures (most of which are not required) all contribute to user overload, stress, and mistakes. The purpose of the BMR is to provide essential guidance to the user, and provide an accurate and reliable history of events — the who, what, when, and how. Unnecessary complexity slows everything down, dilutes essential accountability, and increases risk. Here’s a helpful white paper on batch record simplification: Improving Human Reliability – Batch Record Simplification.
2. No, No, No, And No: Less Is More
Jobs believed success is determined by what you STOP doing. He would be telling us, “Just focus on doing the basics exceptionally well, and forget the rest. If you try to do everything [which translates to initiative overload], you will fail.”
Your call to action:
Tune up your change control system. If your change control system approves everything, it’s dangerous. A good change control systems works on the tried and tested principles of Pareto. A good system only approves the 20% of changes that provide 80% of benefit — those vital few. For more on change management, check out the free webinar Change Management – Best Industry Practices.
Hone your risk management skills. “Less is more” requires good judgment. Whether your change control system approves or rejects planned changes, one thing remains constant: RISK. To make the right decisions, you must have excellent risk management skills and competencies. Take a look at this short video for guidance: Risk Based Decision Making.
3. Hire People Who Break The Rules
Steve Jobs liked to challenge convention — and, on occasion, break the rules. This recommendation will have many industry veterans running for the hills. Employing rule-breakers in an industry that prides itself on “compliance”? Are you kidding? Think about it another way: Rule-breakers are simply those who keep pushing the boundaries. They keep challenging. They keep asking “why”… and they never give up. History proves Jobs was right.
Your call to action:
Rethink your recruiting practices. If companies recruit the same types of employees, they get just that: the “same” in everything. The same decisions and the same outcomes; and, ultimately, maintenance of the status quo. But, in an era of “brutal disruption,” the status quo is no longer good enough. The pharma/biotech industry desperately needs people who think differently — more “why?” people
Allow rule-breakers to do what they do. Progress, in every walk of life, is usually made by rule-breakers; those who are always looking for a different way.
Don’t just recruit people from the traditional sources, such as the pharma/biotech company next door — unless you want more of the same. Try attracting candidates from the automobile and microelectronics sectors. They have been practicing “total quality management (TQM)” for over 50 years!
If you want a lesson in how to manage quality, keep things simple and be laser focused on the end user. Hire people with backgrounds in fast-moving consumable goods. Instead of taking on graduates with “traditional” science degrees, take a walk on the wild side. Recruit a few with degrees in philosophy — people who think differently.
Hire people who know how to think. My Dad, who came from very humble beginnings, used to say, “We don’t have much money, so we have to really think.” The upside of falling prices for our medicines and rising manufacturing costs is that we all have to think differently. So, remember to hire based on two things: character and creative thinking ability.
4. Become Obsessed With …
… finishing and following up! Jobs was a “details person.” A recent survey conducted by Harvard Business Review found that a large percentage of changes and new initiatives fail because of poor implementation and follow-up.5 At NSF, we’ve found the same. For example, most deviation and CAPA (corrective and preventive action) systems have no “effectiveness checks” to make sure the corrective and preventive actions have been implemented correctly and are working. The same goes for many audit and self-inspection programs.
Your call to action:
Become obsessed with disciplined execution, implementation, and follow-up! The pharma industry is populated with very bright people who come up with lots of very bright ideas … that usually fail. The root cause? Poor (ill-disciplined) implementation. This is compounded by no follow-up to see what has worked and what hasn’t. We just need to apply Deming’s PDCA (Plan – Do – Check [measure and follow up] – Adjust).
5. Keep The Main Thing, The Main Thing … Or Die
Jobs was obsessed with satisfying his customers, the end users of his products and services. If you’ve ever been in an Apple Store for repairs or service to your Apple device, you know what I mean. From the minute you enter the store, you are “the main thing.”
Whenever I visit companies, I always ask the people I meet — from the warehouse supervisor to the CEO — about their products and patients. Do they really understand how their products work? Do they really understand every one of their products’ key quality attributes? Crucially, do they really understand how their products improve patients’ quality of life?
Over the last 37 years working in the pharma/biotech industry, I’ve consistently observed one thing: Those who put more focus on the monthly “P&L” (profit and loss) spreadsheet and forget patients’ struggles falter, and, in extreme cases, go out of business. In contrast, companies who keep their patients at the center of everything they do flourish, going from strength to strength.
Your call to action:
Simply conduct the “patient test.” Ask everyone you meet about the products you make and the impact they have on your patients. Ensure that everyone is emotionally connected to the patient. If not, you really are in trouble. Many companies put the “patient first,” using posters and slogans that, in time, become meaningless words; invisible and soon forgotten. One of the most important jobs of leaders at the ground level is to keep people motivated by giving them a reason to care about what they do. This means constant reminders that the patient is at the center of every decision — and this must be communicated not by using flashy posters or slogans, but through the actions of leadership
Don’t allow stress to eat away at your motivation. I am continually amazed by the quality, integrity, and commitment of the people I meet in the pharma/biotech industry. However, the “routine” of working in a highly pressurized, 24/7 world can be dangerous. The hours consumed by emails and meetings; the obsession with measuring things that don’t really matter; the pressure to hit manufacturing, testing, and product release deadlines can cause our patients, “the main thing,” to be forgotten.
Should Pharma Become More Like Apple?
Well, that’s a yes and a no. One thing is for sure: The pharma/biotech industry must get better at “stealing with pride,” rather than reinventing the wheel. Many of the challenges and problems we face are not new. In fact, the answers are already out there. The solutions are waiting to be stolen. Want to know about human error reduction? Study the solutions generated by the aviation industry. Want to know how to write user-friendly, error-free SOPs? Take a look at the IKEA process for designing instructions for furniture assembly. Want best-in-class practices for problem solving, deviation, and CAPA? Take a look at a Toyota car assembly line. Want to know how to use “Big Data”? Look no further than Amazon. So, whether it’s from Apple, Amazon, or anyone else, start stealing with pride!

Sandeep Singh Dhillon
Drug makers May Lose $390 Billion In Sales Over 5 Years –
Pharma Notables

Shares of large drugmakers and biotech companies have surged in recent weeks on optimism that President Donald Trump will scrap his populist rhetoric about curbing escalating drug prices. But the industry nonetheless received a shot of sobering news this week from one of the industry’s most respected forecasters.

Slashed Sales Ahead

EvaluatePharma, a division of health care market intelligence firm Evaluate Group LTD., has cut its global revenue projections for drugmakers by about $390 billion over the period from 2017 to 2022, according to the Financial Times. “The continued political and public scrutiny over the pricing of both the industry’s old and new drugs is not going to go away,” Antonio Iervolino, head of forecasting at Evaluate, told the FT. This is the first time in a decade that London-based Evaluate has cut its drug industry revenue forecast, the FT says.

Price Resistance

Whatever orders or proposals eventually may emanate from the Trump White House, pharmaceutical companies are facing increasing resistance as they attempt to persuade insurers and the U.S. government to pay premium prices for their products, the FT says. As a result, sales of several new heart medicines have been disappointing, the FT indicates. These include Repatha from Amgen Inc, Praluent from Sanofi SA and Entresto from Novartis AG.

According to the FT, these companies include AbbVie Inc. Allergan PLC, Novo Nordisk A/S and Sanofi. Apparently unconcerned about courting favorable public and political opinion is Pfizer Inc, which jacked up the list prices of more than 90 drugs by an average of 20%, the FT adds.

The impact is already clear across the industry. Fed Chair Janet Yellen has noted lower drug prices as a factor in tamer inflation readings. Research firm SSR, for example, says the the list price of branded prescription drugs rose only 6.5 percent in this year’s first quarter, a dramatic slowdown from the 10.9 percent increase during the same period last year. After discounts, net prices actually fell by 1.2 percent, according to SSR as quoted by the FT.

Trump Slams Drug Prices

It’s still unclear whether Trump will retreat from his attack on high drug prices. He once claimed that pharmaceutical companies are “getting away with murder,” as quoted by Bloomberg. Indeed, a statement from the White House indicates that a meeting was held last Friday “as part of the ongoing discussions to reduce the burden of the high cost of drug prescriptions,” per the FT. Trump is expected to issue an executive order on the matter in the near future, according to the FT and various news outlets cited by Bloomberg.

Trump Turns Industry-Friendly

The nature of Trump’s executive order may be more industry-friendly than previously anticipated, Bloomberg reports. “It just sounds more and more likely that the focus is going to be on removing barriers to entry rather than a direct attack on pricing,” as Brian Skorney, an analyst at wealth management and investment banking firm Robert W. Baird & Co. Inc., told Bloomberg.

Instead, Bloomberg cites a Kaiser Health News report that Trump’s “Drug Pricing and Innovation Working Group,” headed by a former pharmaceutical industry lobbyist, is focusing on a number of proposals. They include extending the patent life of drugs in foreign markets, stimulating competition in the U.S. drug market, issuing U.S. government debt to help drug companies pay for expensive treatments, and so-called value-based agreements that link insurance reimbursements to drugs’ actual effectiveness. Other topics of discussion in the Trump White House are, per various news reports reviewed by Bloomberg, promoting cooperative agreements between drug manufacturers and insurance companies, accelerating approval of new treatments, and finding ways to get other countries to pay more for drugs, While the drug industry supports value-based agreements, it also seeks relaxation of federal rules that mandate discounted prices to hospitals that serve low-income patients, Bloomberg adds.

Initially, Democratic Representatives Elijah Cummings of Maryland and Peter Welch of Vermont, members of the House Committee on Oversight and Government Reform, had been encouraged by a meeting with Trump in March to discuss drug prices. But on Wednesday, in a letter to Trump, they expressed dismay over proposals that would work “in favor of the very pharmaceutical lobby that you warned of,” as quoted by Bloomberg.

Read more: Drugmakers May Lose $390B In Sales Over 5 Years | Investopedia
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Sandeep Singh Dhillon
3 new research findings on diabetes treatments – MIMS Malaysia
Pharma Notables
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A recent study shows that diabetes drugs are not only beneficial for the targeted disease, it can also lower the risk of heart failure and renal disease. Here are a few new research findings on diabetes research.

1. Diabetes drugs diminish risk of heart failure and renal disease

In another study, SGLT2 inhibitors have been demonstrated to reduce the risk of a very important cardiovascular condition – heart failure. Heart failure continues to be one of the leading causes of mortality globally.

The results from the study showed that patients with type 2 diabetes who took canagliflozin had a 33% lower risk of hospitalisation for heart failure.

SGLT2 inhibitors have another salient benefit – their ability to significantly lower the risk of renal disease. The patients in the study were also found to have reduced risk by 14% for cardiovascular disease and 40% for “serious kidney decline”.

The diminished risk of cardiovascular and renal disease is likely to be a consequence of these drugs extruding excess glucose from the body. This therefore reduces vascular complications such as atheroma formation, arterial stenosis and hypertension.

2. BCG vaccine may potentially reverse type 1 diabetes

Recently, researchers have found a revolutionary use for the Bacillus Calmette-Guerin (BCG) vaccine, which has been traditionally employed for protection against tuberculosis.

The main aetiology of type 1 diabetes is autoimmune in nature, which involves immune cells such as antibodies initiating destruction of beta cells in the pancreas. The BCG vaccine has been demonstrated to halt this process by increasing the numbers of regulatory T cells which counteract the autoimmune destruction of pancreatic islet cells.

“Repeat BCG vaccination appears to permanently turn on signature Treg genes,” said Denise Faustman, the principal conductor of the research. “… the vaccine’s beneficial effect on host immune response recapitulates decades of human co-evolution with mycobacteria, a relationship that has been lost with modern eating and living habits.”

These new discoveries in relation to diabetes mellitus show great potential for revising current treatment regimens for diabetes. The preventative effects of the BCG vaccine against type 1 diabetes can also reduce the debilitating effects of this disease and therefore reduce overall prevalence of diabetes.

3. Life-threatening ketoacidosis a potential side-effect of diabetes drug

Diabetic ketoacidosis is a life-threatening emergency which requires expeditious treatment with insulin and fluid replenishment. Its clinical manifestations include elevated respiratory rate, vomiting, muscle weakness and overwhelming fatigue.

Typically, this condition is generally a concern with patients with type 1 diabetes, however ketoacidosis has been noted in Type 2 diabetics treated with SGLT2 inhibitors.

The research study compared SGLT2 inhibitors with DPP-4 inhibitors – the findings revealed that SGLT2 inhibitors were twice as likely to induce diabetic ketoacidosis in comparison to DPP-4 inhibitors.

A statistic suggests that approximately between five to eight individuals for every 1,000 individuals given SGLT2 inhibitors will develop diabetic ketoacidosis. Whilst the overall incidences of diabetic ketoacidosis are low, Dr. Michael Fralick, one of the study authors, believes that the actual number may be higher than the study’s findings.

“This is a side effect that’s usually seen in patients with type 1 diabetes mellitus – not type 2 – so doctors are not ‘on the lookout’ for it,” explained Fralick.

“That means that the risk of this side effect might actually be even higher than what we found due to misdiagnosis/under recording.” MIMS

Sandeep Singh Dhillon
Pharma’s Not So Stingy With R&D After All – Forbes
Drug Discovery, Pharma Notables

By Frank David

Many pharma critics argue that drug companies skimp on research while earning outsize revenues–but a new analysis my colleague and I just published tells a more nuanced story.

First, some background. Journalists and academics often point to the fraction of revenues that drug companies spend on research versus “sales, general and administrative” (SG&A) expenses as evidence that pharma underfunds research. But as Derek Lowe (here, here) and others have noted, these analyses provide zero insight into whether spending in each category is too high, too low or just right. Just as households need to spend money on food and utilities, pharma companies need to pay for both SG&A (which includes not just commercial expenses, but also corporate infrastructure) and R&D, and it’s impossible to say a priori which should be a larger fraction of top-line revenues.

Instead, it’s more pertinent to ask about how the growth rates of R&D, SG&A and revenue are related. I think many critics and lay readers would reflexively assume that even when adjusted for inflation, pharma’s revenues have increased year over year, while R&D spending may have stayed constant or even declined.

But that’s not the case, as my Pharmagellan colleague Richa Dixit and I found in our new paper in Nature Reviews Drug Discovery (contact me for a PDF). We examined financial data from 2005 to 2015 for the 10 largest R&D spenders among public big pharma. Looking at the group as a whole, we found the inflation-adjusted compound annual growth rate (CAGR) for R&D (+1.76%) over that period exceeded that of both revenue (-0.01%) and SG&A (-1.12%). And this pattern of the change in R&D spending growth outpacing those of both revenues and SG&A also held true for most of the individual companies. (See note at the end for some additional analysis.)

R&D spending, revenue and selling, general and administrative (SG&A) expenses for each company were converted into US$ as needed, inflation-adjusted (using US inflation rates) and normalized to 2005 values. The compound annual growth rate from 2005 to 2015 for each metric is shown in the colored boxes.Another common belief among critics is that when times get tough in pharma, R&D is the first thing to get slashed–but in fact, that appears to be an oversimplification as well. We looked specifically at instances when a company’s revenue declined by more than 5% (inflation-adjusted) and asked how the drugmaker responded in the following year. Even in the face of steep revenue drops, R&D mostly either increased (9/20) or decreased by a lesser percentage than SG&A (5/20), suggesting that companies often strive to protect R&D even in the face of acute financial pressure.

R&D and SG&A spending by companies in response to large revenue declines. Each data point is from a year in which revenues decreased by >5% compared with the previous year, and reflects the change in R&D and SG&A spending from that year to the subsequent year. All revenue, R&D and SG&A percentages reflect inflation adjustments. See original article for details.Importantly, that last point counters not just a dominant narrative from pharma critics, but also one of the industry’s key arguments against price controls. Price hikes are a major driver of pharma revenue growth, and it’s hard to predict what might happen to the biopharma ecosystem if that growth were constrained. However, these data suggest that large drugmakers are generally committed to sustaining R&D, and many manage to grow research spending even in the face of both acute and longer-term revenue declines. In other words, pharma’s R&D spending may be more strategic than algorithmic, and the simple assumption that lower revenue growth would lead companies to invest less in drug research may not be entirely accurate.

Note: Instead of calculating CAGRs (which only depend on the starting and ending values in the series), one can look at the slopes of the best-fit lines for each 10-year data series, which yields slightly different numbers but essentially the same story; see table below. Using this approach, we found that the annual growth rate of R&D spending (+1.3%) still exceeds that of both revenue (+0.24%) and SG&A cost (-0.80%) for the total set of companies. The rate of growth in R&D exceeds that of SG&A in eight of the 10 individual firms, and it exceeds that of revenue in seven of 10. (For reference, in the published paper, R&D CAGR exceeded SG&A CAGR and revenue CAGR in 9/10 and 8/10 firms, respectively.)

Slopes of best-fit lines for inflation-adjusted R&D spending, SG&A costs, and revenues, 2005-2015. See text for details.Thanks to Chris Franco (Takeda) and Scott Innis (Biogen) for input on drafts of the research cited here. Feel free to email me with questions or for a copy of the article.

Frank S. David, MD, PhD leads the biotech consultancy Pharmagellan, and is the co-author of “The Pharmagellan Guide to Biotech Forecasting and Valuation.”