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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.”

Sandeep Singh Dhillon
Former Pfizer Scientist Is Resurrecting Projects To Solve The Multidrug Resistant Bacteria Problem – Forbes
Pharma Notables

In 2008, Pfizer decided to reduce its therapeutic area footprint and to halt R&D in a variety of areas, including infectious diseases. At the time, Dr. Michael Dunne was a vice-president at Pfizer responsible for its infectious diseases portfolio. After 16 years at Pfizer, Dr. Dunne needed to move on and became the Chief Medical Officer at Durata Therapeutics, where he was able to continue to work on his mission of developing new antibiotics.

Although he stopped working for Pfizer, Dr. Dunne didn’t forget about his former projects. One in particular captured his interest – dalbavancin, a long-acting semisynthetic lipoglycopeptide antibiotic useful as an intravenous treatment for acute skin infections caused by susceptible gram-positive bacteria. Dr. Dunne believed that dalbavancin had great potential and so Durata approached Pfizer to license the drug. Durata’s efforts were successful and Dr. Dunne was back shepherding the dalbavancin clinical program. Five years later, Durata was able to win FDA approval for this antibiotic. Shortly thereafter, Durata Therapeutics was acquired by Actavis (now Allergan) for $675 million. Dr. Dunne’s instincts concerning dalbavancin were on the money.

Despite this success, Dr. Dunne wasn’t done with Pfizer and his former anti-infective portfolio. He has joined Iterum Therapeutics as its Chief Scientific Officer and has again reached out to Pfizer, this time for a penem antibiotic, sulopenem. Here is what he has to say about his latest venture.

“Pfizer stood down from anti-infective drug development in 2008 and that included any of the ongoing work on sulopenem. Sulopenem is a penem antibiotic, similar in spectrum to ertapenem, including multidrug resistant gram negative bacteria. Its main attraction is the fact that, in addition to an intravenous preparation, it is orally available, which will allow for step-down therapy for hospitalized patients coming off their IV therapy, as well as treatment of outpatient infections due to resistant pathogens. Having worked on sulopenem while I was at Pfizer, I recognized its continued relevance to today’s problem of multidrug resistant infections. Pfizer quickly recognized it would be better to have someone continue the development efforts rather than have the drug just sit on the shelf. The license is fairly typical for these types of compounds but, unless Iterum chooses not to develop it further, there are no claw back rights.”

While this is an old compound, sulopenem has good patent protection. The IV product should garner ten years of regulatory exclusivity in the U.S. due to its status as a “Qualified Infectious Disease Product”. Given that the oral prodrug form of sulopenem is an NCE, patent protection for this version exists through 2028 with the possibility of Hatch-Waxman as well as pediatric use extensions.

But, is the commercial attractiveness of sulopenem limited given that the FDA wants to minimize the use of new antibiotics to slow down the inevitable rise of drug resistance? Dr. Dunne doesn’t think so.

“The commercial attractiveness of any new drug is directly related to the patient problem that it solves. Given the medical need it addresses, we believe there is a strong and attractive business rationale for sulopenem. We are fully aligned with the idea that new and potent antibacterial agents should target patients who need them most. The use of sulopenem for step down therapy is perfectly aligned with good stewardship principles that get patients out of the hospital to avoid the propagation of nosocomial infections. In the outpatient setting, specifically for uncomplicated urinary tract infections, we envision that most use will be for two groups of patients. The first is for those who live in regions where resistance to the standard agents now exceeds 15 – 20%, making them poor alternatives for empiric therapy. The second group is for those patients with infections documented to be due to multidrug resistant gram-negative bacteria.”

So, Dr. Dunne has gone back to the Pfizer well in order to bring patients much needed novel antibiotics. Hopefully, for all of our benefit, his successful track record will continue.

Sandeep Singh Dhillon
‘Wow.’ In A First, FDA Requests An Opioid Be Pulled From The Market – Forbes
Pharma Notables
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By Matthew Herper

In a dramatic first, the Food and Drug Administration is requesting that a manufacturer, Endo Pharmaceuticals, remove an opioid drug, Opana ER, from the market because of its potential for causing abuse.

“We are facing an opioid epidemic–a public health crisis, and we must take all necessary steps to reduce the scope of opioid misuse and abuse,” said FDA Commissioner Scott Gottlieb in a prepared statement. “We will continue to take regulatory steps when we see situations where an opioid product’s risks outweigh its benefits, not only for its intended patient population but also in regard to its potential for misuse and abuse.”

“Wow,” said Andrew Kolodny, the director of the Opioid Policy Research Collaborative at Brandeis University. “This is the first time I’ve seen FDA pull an opioid off the market.The question is will they stop here? Because there are some opioids where at least the upper doses should come off the market.”

Opioid overdoses killed 33,000 Americans in 2015, with half of those involving a prescription opioid. Overuse and abuse of the drugs have become a national crisis, and have also helped spur the use of illicit drugs like heroin.

Opana ER was approved in 2006 for patients who need round-the-clock pain relief. In 2012, Endo reformulated the drug to make it more resistant to physical and chemical tampering that makes it easier to abuse, for instance, by crushing and snorting. While the drug met the standards for approval, FDA says Endo never showed that the reformulation would reduce abuse, and Opana was never allowed to claim that it would in marketing materials.

Instead, the new formulation seemed to lead to a spike in intravenous use of Opana. Users would inject the new formulation, instead of crushing and snorting it. This change in behavior led to an HIV outbreak in Indiana. In a statement, Janet Woodcock, the head of the FDA’s Center for Drug Evaluation and Research, specifically attributed the decision to recommend Opana’s removal with that outbreak.

In March, an FDA advisory panel recommended that Opana should come off the market. But Kolodny, for one, was skeptical that it would happen. The FDA generally follows the recommendations, but not always. In 2013, the agency approved a new opioid, Zohydro, despite the fact that an advisory committee panel had recommended 11-2 that Zohydro should stay off the market.

Kolodny vocally opposed the selection of Gottlieb as FDA commissioner because of his ties to drug companies. But Kolodny now says he’s encouraged by this decision. “Maybe, like they say, only Nixon could go to China,” Kolodny says. “Maybe he will make the changes that have been needed for a long time.” The first other drug on Kolodny’s list? Subsys, the Binaca-like fentanyl spray made by Insys Therapeutics. It’s supposed to be used for cancer patients, but there is evidence it was marketed to people who did not have cancer. “That spray is like a lethal weapon,” Kolodny says.

Oxycontin was removed from the market when an abuse-resistant form became available, but that was done at the behest of manufacturer Purdue Pharma, not at the FDA’s request.

If a manufacturer chooses not to honor the FDA’s request to removing a product from the market, the agency can take legal action to force it to do so.

Last year, Opana ER generated sales of $159 million, down significantly from its peak of about $300 million. Endo has annual sales of $4 billion. In a statement, Endo said it is “evaluating the full range of potential options” and emphasized its “strong sense of responsibility” to patients. Shares in Endo traded down 13.6% to $11.90 in after-hours trading.

Sandeep Singh Dhillon
Former Pharma Rep Now Helps Doctors Save Money on Drugs –
Pharma Extra, Pharma Notables
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As a drug salesman, Mike Courtney worked hard to make health care expensive. He wined and dined doctors, golfed with them and bought lunch for their entire staffs — all to promote pills often costing thousands of dollars a year.

Now he’s on a different mission. When Courtney calls on doctors these days, he champions generic drugs that frequently cost pennies and work just as well as the kinds of pricey brands he used to push.

Instead of big pharma, he works for Capital District Physicians’ Health Plan (CDPHP), an Albany, N.Y., insurer. Instead of maximizing pill profits, his job is to save millions of dollars by educating doctors about expensive prescriptions and the stratagems used to sell them.

“Having come from big pharma, I do really feel my soul has been cleansed,” laughs Courtney, who formerly worked for Pfizer and Johnson & Johnson. “I do feel like I’m more in touch with the physicians” and plan members, he added.

As a drug salesman, Mike Courtney worked hard to make health care expensive. He wined and dined doctors, golfed with them and bought lunch for their entire staffs — all to promote pills often costing thousands of dollars a year.

Now he’s on a different mission. When Courtney calls on doctors these days, he champions generic drugs that frequently cost pennies and work just as well as the kinds of pricey brands he used to push.

A pharmacist works at a pharmacy in Toronto
Instead of big pharma, he works for Capital District Physicians’ Health Plan (CDPHP), an Albany, N.Y., insurer. Instead of maximizing pill profits, his job is to save millions of dollars by educating doctors about expensive prescriptions and the stratagems used to sell them.

“Having come from big pharma, I do really feel my soul has been cleansed,” laughs Courtney, who formerly worked for Pfizer and Johnson & Johnson. “I do feel like I’m more in touch with the physicians” and plan members, he added.

Costs for prescription drugs have been rising faster than those for any other health segment, marked by high-profile cases such as the reported 400 percent increase for Mylan’s EpiPen and 5,000 percent spike for Turing Pharmaceuticals’ Daraprim.

Health plans and others paying those costs are fighting back. Many have tried to give doctors academic research on pill effectiveness or simply removed high-cost drugs from coverage lists.

Consumer groups and medical societies have tried to spread the word about expensive drugs. Startup GoodRx lets patients compare retail prices online.

CDPHP is one of the few insurers to have taken the battle against pricey pills a step further. It is recruiting across enemy lines, hiring former pharma representatives and staffing what may be a new job category: a sales force for cost-effective medicine.

“Insurers are taking matters into their own hands,” said Lea Prevel Katsanis, a marketing professor at Canada’s Concordia University who specializes in the pharmaceutical industry. “They’re saying, ‘We can’t really rely on drug companies to talk to doctors about what’s cost-efficient.’”

If insurance companies can curb drug costs, premiums paid by employers, taxpayers and consumers need not rise as fast.

Two years ago, when one company increased the cost of a common diabetes medicine to 20 times what it had been a few years earlier, Courtney and five other former pharma and medical-device reps working for CDPHP knew what to do.

Valeant Pharmaceuticals had cranked up the price of one common dosage of its Glumetza medicine for lowering blood sugar to an astonishing $81,270 a year, according to Truven Health Analytics, a data firm. Meanwhile a similar, generic version can be bought for as little as a penny a pill.

Because Glumetza was on CDPHP’s list of approved drugs, the insurer and its members had to pay for it when doctors prescribed it, resulting in millions in extra costs and stinging copayments for patients.

Dr. Eric Schnakenberg, an upstate New York family medicine doctor, was shocked when patients began complaining about what he assumed was an inexpensive prescription. Doctors are famously unaware about the cost of the care they order, a situation exploited by drug sellers and other vendors.

While physicians’ electronic prescribing programs and even pharmaceutical guides like the Physicians’ Desk Reference contain prescribing information — some are even peppered with ads — they contain no specific information about prices. Drug sales reps who visit their offices don’t highlight high prices as they drop off free samples, and drugmakers can quietly, but substantially, hike the price of a drug from one year to the next.

“As physicians, we’re blindsided by that,” Schnakenberg said. “We get patient complaints saying, ‘Hey, I can’t afford this,’ and we say: ‘It’s cheap!’”

After Courtney and his colleagues alerted doctors to what Valeant was up to, all but a handful of the 60 plan members who were taking Glumetza switched to metformin, the generic alternative. That saved about $5 million in a year.

Following an outcry over its practices, Valeant agreed last year to raise annual prices by no more than single-digit percentages, the company said through a spokesman. But such hikes could still outpace the inflation rate.

Cardiologist John Bennett got the idea to hire pharma reps a few years ago, after he became CDPHP’s chief executive. He knew reps are smart, genial and motivated. Overhiring by pharma had put many back on the job market.

His sales pitch to them, he says half-jokingly, was: “You know everything they taught you in big pharma? How would you like to use those powers for good?”

Pharma companies spend billions on TV ads, doctor blandishments and expensive salespeople to keep prescriptions flowing.

Pfizer, Johnson & Johnson and other sellers responded to critics a few years ago by restricting gifts of entertainment, coffee mugs and some meals. But the industry’s ethics code still allows lavish consulting contracts for doctors and sponsorship of physician conferences as well as meals for doctors and their staffs who listen to an “informational presentation” from sales reps touting expensive pills.

“When those products go generic, nobody’s promoting them anymore,” Courtney said. Generics makers lack big marketing budgets. CDPHP’s remedy: The insurer promotes generics with its own reps.

“It’s a great idea,” said Alan Sorensen, an economist at the University of Wisconsin who has studied drug prices. “Even a small moving of the needle on their [doctors’] prescribing behavior can have a pretty big impact on costs.”

At first the team concentrated on educating doctors about cheaper alternatives to Lipitor, a widely prescribed cholesterol-lowering medicine, and Nexium, for stomach problems. That saved around $10 million the first year, much in the form of copayments that would have been owed by plan members.

Recently the plan has focused on Seroquel, a branded antipsychotic that costs far more than a similar generic. Switching to the generic saves $600 to $1,000 a month, estimates Eileen Wood, the insurer’s vice president of pharmacy and health quality.

CDPHP’s repurposed reps have helped keep the insurer’s annual drug-cost increases to single-digit percentages, whereas without them and other measures “we would certainly be well into double-digit” increases, she said.

Educating doctors about drug costs is part of a larger push for “transparency” in an industry where Princeton economist Uwe Reinhardt says consumers face the same experience as somebody shopping in Macy’s blindfolded.

Current research by the University of Wisconsin’s Sorensen finds physicians with access to data about drug prices and insurance coverage are more likely to prescribe generics.

That gives Courtney and his colleagues a fighting chance, even if, he said, “we don’t have the freewheeling, unlimited green Amex card like I did back in the day.”

Sandeep Singh Dhillon
Sulfonylureas for Diabetes Still Have a Role; Cost a Big Factor – Medscape
Pharma Notables
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SAN DIEGO — A talk on whether sulfonylureas still have a role in the contemporary treatment of type 2 diabetes garnered much interest here at the American Diabetes Association (ADA) 2017 Scientific Sessions.
Speaking to a large audience in a packed room, Kamlesh Khunti, MD, from the University of Leicester, United Kingdom, presented a fast-paced overview of the history of the use of sulfonylureas, randomized controlled trials vs observational data, mechanism of action, novel insights, and practical considerations.
While there is universal agreement that metformin should be the treatment of first choice in type 2 diabetes, there is still much debate about which of the many classes of drugs should be used second line, when metformin alone isn’t sufficient to control blood glucose.
“I don’t think you can throw away sulfonylureas completely; there are a lot of data showing that they can be beneficial, and a lot of it comes down to affordability,” Dr Khunti told Medscape Medical News following his talk.
There is extensive experience in using them, and the risks and benefits are reasonably well-understood, he stressed.
While the larger database studies may show that sulfonylureas are not as good as other type 2 diabetes drugs, in the randomized controlled trials, the data on efficacy, safety, and durability “are pretty reasonable….There is still a place for sulfonylureas…and in the UK, we still use them a lot,” he added.
On the other hand, “If affordability is not a problem, we don’t have a question,” he noted, implying that if cost were not a factor, he would choose a second-line agent other than a sulfonylurea.
Session chair Neda Rasouli, MD, University of Colorado, Aurora, told Medscape Medical News that with many newer class of medication to treat type 2 diabetes coming to the market, “some leaders in the diabetes field are saying that maybe there is no room for sulfonylureas.”
But “it’s hard to let them go because of the low cost,” she acknowledged, adding, “Everybody wants to make sure that they are using a medication that is safe, and that’s why I think there is great interest.”
However, “if cost werenot a factor, probably people wouldn’t use sulfonylureas,” she also acknowledged.

CAROLINA and GRADE Will Help Inform Choice

The extensive review presented by Dr Khunti at the ADA meeting showed that there are concerns about side effects such as hypoglycemia and weight gain with sulfonylureas, but the data were inconclusive about potential cardiovascular harm, Dr Rasouli noted.
Dr Khunti said: “We really need to [see] the head-to-head comparisons that we are all eagerly waiting for.”
These include data from the cardiovascular-outcome study of the dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin (Tradjenta, Lilly/Boehringer Ingelheim) vs the sulfonylurea glimepiride in patients with type 2 diabetes (CAROLINA).
And findings from the Comparative Effectiveness Study of Major Glycemia-lowering Medications for Treatment of Type 2 Diabetes (GRADE) study. GRADE is comparing four commonly used diabetes medications — the sulfonylurea glimepiride, the DPP-4 inhibitor sitagliptin (Januvia, Merck), the glucagon peptide-1 (GLP-1) receptor agonist liraglutide (Victoza, Novo Nordisk), and insulin glargine — head to head, when added to metformin. Patients will be followed for 4 to 5 years, and “that study will help us to decide what the best medication is after metformin,” Dr Khunti noted.
Both studies are expected to complete their data collection for primary outcomes in February 2019 and August 2020, respectively, and the results will help guide clinical practice, Dr Rasouli agreed.
However, GRADE does not include sodium-glucose cotransporter 2 (SGLT2) inhibitors, and one of these agents, empagliflozin (Jardiance, Boehringer Ingelheim) was the first type 2 diabetes medication to show cardiovascular protection in the landmark EMPA-REG OUTCOME study reported in September 2015.
Two glucagon peptide-1 (GLP-1) agonists have since also shown this, liraglutide in LEADER and the investigational agent semaglutide (Novo Nordisk) in SUSTAIN-6.
“It will be interesting to see if other SGLT2 inhibitors and GLP-1 receptor agonists are cardioprotective,” Dr Rasouli commented to Medscape Medical News. “Then you might consider them as a second agent, but if [trials] don’t confirm it, then we go back to the costs of the medication.”She also noted that “right now, in the ADA guideline, basal insulin can be used after metformin, but there is clinical inertia, and not everybody is comfortable with starting an injectable therapy as a second agent.”
Can’t Ignore Cost When Considering Diabetes TherapiesStressing the importance of cost, Dr Khunti said: “Worldwide, 415 million people have diabetes, and 80% live in low–middle-income countries.” And price is an important consideration even for developed countries, he emphasized.
Diabetes UK has said that the costs of treating diabetes threaten to bankrupt the National Health Service, for example.
There “is a massive difference” in cost for an annual supply of antidiabetic agents, which, in the United States, ranges from $96 US for glipizide and $192 for glyburide — both sulfonylureas — to $1243 for generic metformin to around $5000 for DPP-4 inhibitors and around $5400 for SGLT2 inhibitors, he noted.
A recent study reported that sulfonylureas are still used by 31% of patients with diabetes in the United States, and rates of use are even higher in Europe — 41% to 45% of patients in the United Kingdom and 47% of patients in the Netherlands use a sulfonylurea, he added.
There may however be differences between countries in the type of sulfonylurea that is used, Dr Khunti explained.
“In the UK, gliclazide is the [sulfonylurea] that is used the most,” he said, noting that it does seem to have a better profile than other sulfonylureas in the ADVANCE trial.
And “over time we have improved and use a lower dose” of gliclazide, he said.
Gliclazide is not available in the United States, Dr Rasouli noted, but glimepiride and glipizide are available.

Get Patients on Whatever Therapy They Can Afford

Summarizing, Dr Khunti said: “What I’ve shown you is there are controversial issues in terms of whether we use sulfonylureas or not, and a lot of it comes down to affordability.”
“We have great drugs, but we are not using them in a timely manner, and…we are waiting far too long to intensify therapy in patients.”
“We should be…getting these patients on whatever therapy we can afford, bringing HbA1c down to control from diagnosis, keeping the HbA1c down for as long as possible, as safely as possible, with whatever therapy is available and affordable to the patient.” That is more likely to generate better outcomes for the patients in the longer term, he explained.
“There’s good efficacy and durability. There’s low risk of hypoglycemia with the second-generation sulfonylureas. We’ve established long-term benefit with decreased risk of micro- and to a certain extent macrovascular complications from randomized controlled trials.”
And sulfonylureas are affordable for the 80% of diabetes patients worldwide who reside in low- to middle-income countries, he reiterated.

Dr Khunti reports that he is a speaker and on the advisory panel for AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Servier, Eli Lilly, Janssen, and Novo Nordisk. He is also a consultant and speaker for AstraZeneca, Novartis, Sanofi, Merck, Janssen, Boehringer Ingelheim, and Servier, and he is a speaker for and receives research support from AstraZeneca, Novartis, Novo Nordisk, Sanofi-Aventis, Eli Lilly, Boehringer Ingelheim, Merck, and Roche.
For more diabetes and endocrinology news, follow us on Twitter and on Facebook.
American Diabetes Association 2017 Scientific Sessions; June 9, 2016; San Diego, California. Session 3-CT-MS04

Sandeep Singh Dhillon
Insurance companies have made it crystal clear how Trump could send Americans’ healthcare costs soaring – BusinessInsider Malaysia
Pharma Notables

We may be roughly halfway through 2017, but insurance companies are already showing just how much President Donald Trump’s policies could rock the Obamacare market.

Insurers have submitted their 2018 plans in seven states and Washington DC for the Obamacare individual insurance exchanges, giving us the first glimpse of how they are digesting the outlook for the healthcare industry under Trump.

Over the past two weeks, two insurers have made it clear just how Trump’s policies could cause healthcare costs for average Americans in these exchanges to increase by more than they would otherwise.

In Pennsylvania, Insurance Commissioner Teresa Miller announced on Thursday that the premium for a baseline Obamacare exchange plan would increase by an average of only 8.8% for 2018 compared to this year. This is lower than the 10.5% increase between 2016 and 2017.

But Miller warned that premiums could go much higher if Trump makes just a few policy changes. According to Miller, if Trump announces he will stop enforcing the individual mandate that compels people to buy coverage, premium requests from insurance companies would increase by an average jump of 23.3%.

Additionally, if Trump stops making cost sharing reduction (CSR) payments, insurers would ask for a 20.3% increase on average. CSR payments offset the cost for insurers of providing lower out-of-pocket costs to poorer Americans. Health policy experts have said the payments are critical and without them, Trump’s predictions of a “collapse” in the market could come true.

If both changes are made, insurers would ask for a 36.3% increase, according to Miller.

“I sincerely hope that Congress and the Trump Administration do not take action that could negatively impact the progress we have made in Pennsylvania,” Miller said in a statement announcing the rates.

Similarly, in North Carolina, Brad Wilson, the CEO of Blue Cross Blue Shield North Carolina (BCBS NC), said that the company was forced to jack up their requested premium due to the uncertainty over the CSR payments and other changes form the Trump administration.

Due to uncertainty over the CSRs, the company requested an increase of 22.9% for the 2018 plan year. BCBS NC said they would have requested a 8.8% raise if not for the payments’ murky future.

“The failure of the administration and the House to bring certainty and clarity by funding CSRs has caused our company to file a 22.9 percent premium increase, rather than one that is materially lower,” Wilson told The Washington Post. ‘That will impact hundreds of thousands of North Carolinians.”

In fact, Wilson said that the market in 2017 was looking solid.

“It’s still early and our numbers for the year run about 30 to 45 days behind. But the analysis underway so far in 2017 appears to show stability in the market in terms of price, utilization, and the customer base,” the CEO told Vox.

Many health policy experts projected that the large jump in premiums for 2017 was a one-off issue as insurers adjusted their plan costs to the relative health of the market and the exchanges became fully phased-in.

It appears in Pennsylvania and North Carolina the exchange markets were close to being stabilized, if not for the uncertainty from the Trump administration.

Sandeep Singh Dhillon
New study finds wide variety in pharma companies’ cancer access programmes – Access to Medicine
Pharma Notables


Amsterdam, the Netherlands, 22 May, 2017 – Today, the Access to Medicine Foundation publishes the first analysis of pharmaceutical company actions to improve cancer care in the developing world. It finds that market leaders in oncology are addressing cancer care for the poor, with 129 separate initiatives up and running. Efforts are spread across cancer types and countries. Female cancers gain most attention.

Cancer is a leading cause of death in every corner of the world. Currently, around 65% of all cancer deaths occur in developing countries, where cancer rates are also rising. Yet many cancers are now curable – provided local healthcare systems can swiftly identify people with cancer and treat them effectively. National governments shoulder the main responsibility for putting these systems into place.

Growing cancer crisis

Growing awareness of the crisis in cancer care in poorer countries has pushed the role of pharmaceutical companies – the developers and owners of cancer medicines – into the spotlight. Some companies have been criticised for aggressively defending oncology patents in poor countries, or for putting high price tags on their newest cancer drugs. Reports are also emerging of worthwhile public–private initiatives to improve cancer care.

To move the debate forward, greater clarity was needed. The Access to Medicine Foundation has systematically mapped which pharmaceutical companies are already taking action to improve access to cancer care in poorer countries, where and for which cancers. It has compared this analysis against each company’s oncology portfolio, including whether it has medicines on the WHO’s Essential Medicines List (EML). The EML identifies medicines that are essential for a basic healthcare system to function.

“We now know which projects are up and running, which tells us a great deal about how companies see their role when it comes to cancer care in countries with weaker health systems,” says Jayasree K. Iyer, Executive Director of the Access to Medicine Foundation. “With this information at our fingertips, the conversation can move forward – to forge more partnerships in this space. I hope that this analysis will inspire pharmaceutical companies to get more involved in improving access to cancer care.”

The Access to Medicine Foundation has mapped whether and how large pharmaceutical companies are improving access to cancer care in low and lower-middle-income countries. It reports on the actions of 16 of the world’s largest research-based pharmaceutical companies by revenue. This includes five of the six largest players in the global oncology market: Roche, Novartis, Bristol-Myers Squibb, Johnson & Johnson and Pfizer (in order of revenue). The global oncology market is expected to grow from USD 105 billion to USD 150 billion by 2021.

Diverse approaches
Together, the 16 companies are implementing 129 separate access initiatives for cancer patients. Roche engages in the highest number of initiatives across the board. Roche is also the market leader in oncology revenues globally.

The majority (71) of initiatives relate to some form of capacity building – aiming to improve the knowledge, skills, infrastructure or technical capabilities of a local cancer care system. These programmes are very varied. A sizeable group aims to build capacity in either cancer diagnosis (16) screening (14) and/or early detection (5). The ability to catch cancer early and give an accurate diagnosis is critical for improving cancer survival rates. The most comprehensive initiatives either combine different access strategies, multiple types of activity per project, or address several forms of cancer.

Figure 2. Which companies access initiatives address more stages of cancer care? Effective cancer management requires a sequence of health services, referred to as “the cancer continuum of care”. It involves many stages. While many companies address multiple stages of the cancer care continuum, five companies stand out: Roche, which addresses more than any other company, followed by AstraZeneca, Pfizer, Bristol-Myers Squibb, Eli Lilly and Merck & Co., Inc. Several initiatives address multiple stages. No company addresses all stages. A few companies support capacity building through philanthropy (not shown here): notably Bristol-Myers Squibb, with 11 such initiatives.The most comprehensive programmes – examples

AstraZeneca’s Project Phakamisa in South Africa aims to improve access to a range of hormonal treatments for breast and prostate cancer through pricing actions, awareness raising, providing patient support and training volunteers and healthcare professionals.
Volunteers from AstraZeneca’s Phakamisa project march to raise awareness of breast and prostate cancer symptoms in South Africa.
Bristol-Myers Squibb and Pfizer are working with a range of partners in a Women’s Cancer Initiative in the Americas. It focuses on breast and cervical cancer and aims to improve national treatment programmes, patient registries and education, while also addressing cancer awareness, screening and early detection.
Eli Lilly is working with Kenyan NGO AMPATH to address access to gynaecology-oncology and general oncology. Its objective is to equip an oncology outpatient center at MOI University Hospital in Eldoret, Kenya, hire medical staff, train local healthcare professionals and create a research and training institute focused on cancer.
A little over a quarter of initiatives address pricing (36 initiatives). Many of these are organised in patient access or support programmes (PSPs and PAPs), which generally provide some form of discount or donation directly to patients enrolled in the programme. Companies are also bringing financial reserves to bear: the study found 17 cases of companies providing philanthropic financial support to cancer care programmes.

Female cancers receive attention

Female cancers, haematological cancers and colorectal cancer gain most attention – more initiatives aim at breast cancer (42 initiatives) and cervical cancer (27) than other cancer types. Among women in developing countries, this reflects the most common cancer types. Among men, however, the most common cancers in developing countries are lung and liver cancer, which seem less represented. The companies in scope have many products for lung cancer.

Companies are engaging in more initiatives in Kenya, China, India, Indonesia and the Philippines than in other countries. This is likely due to the fact that these countries have stronger healthcare systems, broader networks of organisations already addressing cancer care, or more opportunities to have a greater impact on people’s health. Conversely, countries such as Sierra Leone, Somalia and Burundi currently have no cancer access initiatives in place, despite having high cancer mortality rates. This can partly be explained by the fact that these countries have weaker health systems and less attractive markets.

Portfolios lead on breast, lung and prostate cancer products
The 16 companies have a total of 171 cancer medicines and two preventive vaccines in their portfolios. They have the most products for breast, lung, prostate cancer and haematological malignancies (in that order). The companies have 55 cancer or cancer-related products that are on the WHO Model Essential Medicines List (EML). Only 11 EML products (from three companies: AstraZeneca, Novartis and Roche) are incorporated into an access initiative.

“Providing access to cancer care is a huge challenge. How can companies contribute? More than 40 cancer medicines have been singled out by the WHO on its Essential Medicines List as being critical to any cancer care system. Making these products available and affordable in sufficient quantities is a great place to start. With governments in the lead, pharma companies can play a unique role in shifting the dial on cancer care.” – Jayasree K. Iyer, Executive Director, Access to Medicine Foundation.

The Access to Medicine Foundation is an independent non-profit organisation based in the Netherlands. It is funded by the Bill & Melinda Gates Foundation, UK AID and the Dutch Ministry of Foreign Affairs.

Download the study here