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Pharma companies increasingly to focus on stability studies as norms from US FDA, WHO and D&C Rules mandate product safety information
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Indian pharma companies now need to increasingly focus on stability studies to prove the safety of formulation till the end of the shelf life. The industry already has three regulations to adhere: Drugs & Cosmetic Rules, US FDA and WHO stability testing guidelines for API, finished drugs and the ICH norms on the same.

The purpose of the stability testing is to provide evidence on how the quality of a drug substance or drug product varies with time under the influence of a variety of environmental factors such as temperature, humidity and light. It also calls for storage conditions, retest periods and shelf life of the products, said B Kumar, deputy drugs controller, sub-zonal office, CDSCO, Bengaluru.

In order to ensure that the drug formulations marketed in the country are stable till the end of the shelf life, it is necessary that stability studies should be brought under the condition of license for manufacturing drugs especially in Rule 71, 71-B & Rule 76, he added.

Delving on the submission of data for a stability study at the recently concluded seminar organized jointly by the Karnataka drugs control department and the KDPMA, Kumar said these are based on the written and approved stability protocol and not merely based on standard operating procedures. These are generally carried out at quality control laboratories.

With regards to the revised guidance of the D&C Rules, regulatory requirements of stability studies issued on April 10, 2018, mandates the applicants to submit evidence of stability, safety of excipients among others to the State Licensing Authority before grant of product manufacturing license for any product. Schedule M requires the manufacturers to conduct the stability study to ensure stability of the manufactured products too, he said.

The factors affecting stability studies are the storage time, storage conditions, type of storage forms, container and closure system. Here, Kumar went on to state that the longer the storage time, the more potential for degradation of the drug and more deterioration of dosage forms. Even the container closure system may affect the stability of drug. For instance, the plastic containers and rubber closures are reported to absorb antioxidants and preservatives from the solutions in contact leading to destabilization and microbial attack. Some of the stability problems also span from visible to particulate contamination, formation of gas and change in colour, he noted.

The three types of stability testing are accelerated stability studies, intermediate testing studies and long-term stability studies. Further, testing should be done using the containers and closures proposed for storage and distribution. Here the test should also include containers and closures for physician sample, besides promotion and marketing sample and bulk storage sample. The protocol should provide information about type, size and storage of containers and closures. Extensive studies must be done before selection of container-closure system, said Kumar.

Courtesy – Pharmabiz

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Sandeep Singh Dhillon
Biocon Malaysia unit gets FDA Form 483 notice – Times of India
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CHENNAI: Indian pharmaceutical giant Biocon on Wednesday told the BSE that the US-FDA (Food and Drugs Administration) has issued a Form 483 with six observations for its manufacturing facility in Malaysia.
Normally, the US-FDA issues the Form 483 when an inspection finds conditions in violations of food and drug safety. The company’s management is notified via Form 483 if the US-FDA team’s inspection has found “conditions or practices that any food, drug, device or cosmetic has been adulterated or is being prepared, packed, or held under conditions whereby it may become adulterated or rendered injurious to health.”
Biocon told the BSE that it would come up with a corrective action plan.
“The US-FDA has completed a pre-approval inspection of our manufacturing facility in Malaysia and has issued a Form 483 with six observations. As per the normal expectations of the agency, we intend to respond with a corrective and preventive action plan in a timely manner,” said Rajeev Balakrishnan, company secretary, Biocon.
On its website, Biocon lists its insulin manufacturing facility at Johor, Malaysia, as its first overseas biopharma manufacturing and research unit, started in 2015 with an investment of $275 million.
Biocon Malaysia, which has launched biosimilars such as Basalog and Insugen, started commercial operations in 2017 and has GMP certification from the European Medical Agency.
Biocon already supplies insulin from this plant in Malaysia and expects the insulin supplies to Europe upon product approval.
The company has received USFDA approval for Glargine and the same is likely to have triggered the inspection. The company had also indicated of the same in the recently quarterly earning conference call.
Biocon’s biosimilar version of Roche’s Trastuzumab — a drug to treat breast and stomach cancer — received US FDA approval last December.

Sandeep Singh Dhillon
If Amazon And Buffett Lift Veil On Health Prices, Insurers Are In Trouble – Forbes Healthcare
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By Bruce Japsen , CONTRIBUTOR

Jeff Bezos’ Amazon and Warren Buffett’s Berkshire Hathaway are forming their own healthcare company with JPMorgan Chase to increase transparency for their employees, and that could be bad news for insurers and pharmacy benefit managers.

Health insurance companies and PBMs have long said they want to bring more transparency to the U.S. healthcare system, yet consumers often don’t know the true cost of healthcare. Prices are negotiated in secret and doctors don’t often know what their own services cost or what their patients will be charged.

Details of the new company the three corporate giants want to create remain sketchy, but the idea that they want to bring more transparency is one of the disclosed goals. “Our people want transparency, knowledge and control when it comes to managing their healthcare,” said Jamie Dimon, Chairman and CEO of JPMorgan Chase.

Those who’ve been engaged in the struggle to find the true cost of healthcare have been working for years with limited success. Often times, they have difficulty getting data from health plans or medical care providers.

“Resistance to transparency in healthcare remains high,” says Network for Regional Healthcare Improvement CEO Elizabeth Mitchell, who welcomes Amazon, Berkshire and JPMorgan’s new company. “Employers who pay for this care still don’t have insight into the relative value of what they are buying. They are looking for a way to have assurance that they are paying a fair price for a high quality service.”

The Network for Regional Healthcare Improvement has long said any health reform effort needs to look closely at transparency because data that reveals the total and true cost of care is difficult to find. In a report last year, NRHI said health spending by U.S. commercial insurers can vary by $1,000 or more per year per patient, depending on where enrollees live.

The potential for the Amazon-Berkshire healthcare company to disrupt the way health plans do business is one reason shares of many healthcare companies tumbled Tuesday after the partnership was announced.

Shares of insurers like Aetna, Anthem and UnitedHealth Group lost 5% to 10% of their value while pharmacy chains CVS Health, Walgreens Boots Alliance and drug makers with expensive medicines like Abbvie also took a hit on Wall Street. And the big PBM, Express Scripts, also lost more than 2% of its value Tuesday.

Nobody knows for sure what Amazon, Berkshire and JPMorgan have in mind because they said their effort is in its “early planning stages.” The trio tapped three executives to get the company off the ground: Todd Combs, an investment officer of Berkshire Hathaway; Marvelle Sullivan Berchtold, a Managing Director of JPMorgan Chase; and Beth Galetti, a Senior Vice President at Amazon. No further details were disclosed, including where the company would be located.

Some think Amazon could leverage its technology platform to make a dent in the healthcare cost curve and improve transparency.

“Amazon may spur new technology innovations” such as artificial intelligence or information sharing platforms that “can increase the efficiency of healthcare delivery,” said Idris Adjerid, a management IT professor in the University of Notre Dame’s Mendoza College of Business. “Our research substantiates this potential value. We find that technology initiatives, which facilitated information sharing between disconnected hospitals resulted in significant reductions in healthcare spending.”

Studies show 30% of the money spent on healthcare is waste. Amazon, Berkshire and JPMorgan said the initial focus will be on “technology solutions” that will provide U.S. employees and their families with “simplified, high-quality and transparent healthcare at a reasonable cost.”

But given Amazon’s popularity among consumers and the decades of success Buffett has built with his businesses, the executives say improving patient experience and customer service will also be a target of the new company.

“These businesses understand customer service,” Mitchell of the Network for Regional Healthcare Improvement said of Amazon, Berkshire and JPMorgan. “Reorienting healthcare to being customer focused is exactly what is needed and will require massive and overdue change.”

This article originally appeared at https://www.forbes.com/sites/brucejapsen/2018/01/31/if-amazon-and-buffett-lift-veil-on-health-prices-insurers-are-in-trouble/#6a8a085141c0

Sandeep Singh Dhillon
Novartis Climbs Out of Its Growth Pit – Bloomberg Gadfly
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Its new CEO has challenges but is starting from a good place.

By Max Nisen

Incoming Novartis AG CEO Vas Narasimhan is taking over at the right time.

As it reported fourth-quarter earnings on Wednesday, the company predicted it will grow sales in 2018 after a multi-year slump. Departing CEO Joe Jimenez is leaving many difficult decisions for Narasimhan as he cedes control next week. But he is also leaving a company with an unusually rich set of assets and a pretty high margin for error.

One of Jimenez’s nicest parting gifts is a return to sales growth for the company’s troubled Alcon eye-care division. That makes the decision (delayed until 2019) to sell or spin off the unit less urgent; it’s no longer an obvious drag on the share price. And there’s real hope of increasing the return of an eventual divestiture by further improving results.

But generics unit Sandoz has emerged as a new problem child, hurt by a difficult pricing environment. U.S. sales fell 17 percent in the fourth quarter from a year ago, Novartis said Wednesday. Narasimhan on the earnings call outlined a strategy to help Sandoz, moving away from products most subject to pricing pressure and toward more-complex (read, expensive) alternatives. But several other generic drugmakers are pursuing the same strategy, and it won’t be an easy or quick fix.

Sandoz’s success depends largely on the progress of Novartis’s heavy investment in biosimilars — the equivalent of generics for complex drugs made in living cells. But it’s far from alone in that endeavor, and the lucrative U.S. market is proving highly difficult and time-consuming to crack.

On the novel drug side — the source of 67 percent of Novartis’s revenue in 2017 — Narasimhan will inherit a broad set of new medicines to help overcome sales declines of older stalwarts such as Gleevec. But heavy competition awaits. Cosentyx, the firm’s best recent launch, is fighting it out in psoriasis with both well-settled blockbusters such as Humira and newer drugs such as Taltz and Tremfya. Breast-cancer drug Kisquali and an upcoming migraine medicine are also in intensely competitive classes.

Pharmacy benefit managers will likely have a field day extracting big discounts on these drugs, and the marketing battles will be fierce.

Novartis’s heart failure drug Entresto has been dogged by payer restrictions since its 2015 approval due to its cost and large patient population. It’s still far from the company’s diminished $3 billion plus estimate of its potential peak sales.

Still, at least Novartis has new drugs. Some of its medicines are in less-competitive markets. And while I am constitutionally skeptical of Narasimhan’s claims that the company will boost productivity via investment in automation and AI, his pledge to prune the firm’s research pipeline more aggressively is promising.

Though Novartis hasn’t done much on the M&A front, it has the capacity to invest if pharma growth lags once more or if Sandoz proves tough to fix. Its balance sheet is strong. And it can generate a flood of cash by selling out of its consumer joint venture with GlaxoSmithKline PLC and its separate multi-billion-dollar equity stake in Swiss rival Roche Holding AG. It could also speed up its decision on what to do with Alcon.

But its financial position gives it the luxury of waiting for the best return on these disposals while enjoying a cheap boost to its income in the meantime.

There are pitfalls ahead for Narasimhan. But at least he’s not starting in one.

This article originally appeared at https://www.bloomberg.com/gadfly/articles/2018-01-24/novartis-earnings-climbing-out-of-a-growth-pit

Sandeep Singh Dhillon
5 Milestones Of 2017 In The War On Cancer – Forbes Healthcare
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By Arlene Weintraub,

An impressive 45 novel drugs have been approved by the FDA in 2017 so far — more than doubling last year’s total. A dozen of those new products were in oncology, as the year ushered in new choices for treating a range of cancers, including mantle cell lymphoma, Merkel cell carcinoma and follicular lymphoma.

But what’s notable about the FDA’s list of new chemical entities approved during the year is that it doesn’t include many of the other advances that were seen in the world of oncology research. That’s a separate list, which includes novel combinations of previously approved drugs, and the entry of personalized immune-cell therapies—CAR-T treatments—that have offered hope to thousands of patients who had run out of options for treating their cancers.

The bottom line is that it has been a banner year for cancer research. Here were some of the highlights:

May 23: The FDA approves the first cancer treatment that’s prescribed based on the genetic characteristics of the disease—not the tumour’s location. Merck’s immuno-oncology drug Keytruda won approval to treat patients whose tumors are defined as microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR). About 5% of colorectal tumors have one of these two characteristics, but the defects are also found in other solid tumors, such as breast cancer, gastrointestinal cancer and prostate cancer. MSI-H and dMMR tumors are unable to properly repair the DNA inside cells. Keytruda works by blocking “checkpoints” that would normally prevent the immune system from recognizing and attacking these defective cells. Merck tested Keytruda in 149 patients with 15 different MSI-H or dMMR cancer types and charted impressive results: More than 39% of patients had at least a partial response to the drug, and 78% of those people responded well for six months or longer.

August 30: The FDA approves the first CAR-T treatment, Novartis’s Kymriah, for some young people with leukaemia. When results from trials of CAR-T treatments first started emerging a few years back, it seemed too good to be true: Cure rates for previously untreatable blood cancers were 70% and higher. But the results held up, and Novartis took home the first FDA approval in this booming area of cancer research.

Kymriah is made by removing immune-boosting T cells from patients, engineering them to be able to recognize and kill their cancers and then re-infusing them. It’s a hugely complex process for a one-time treatment, and it’s priced at a whopping $475,000. But Novartis has proven to be a pioneer not just in the invention of CAR-T but also in its pricing: The company struck a deal with the Centers for Medicare and Medicaid Services (CMS) stipulating that the agency will only have to pay for the treatment when patients respond within the first month.

October 18: Kite Pharma wins approval for its CAR-T, Yescarta, just weeks after cementing its $11.9 billion purchase by Gilead. When Gilead announced its planned purchase of Kite in August—one of the biggest oncology deals of recent years—no one was surprised. Gilead had been under pressure to make a purchase that would boost its pipeline, and Novartis was on the verge of proving that personalized cell therapies can be embraced by regulators.

Yescarta was approved to treat some adult patients with large B-cell lymphoma. There have been some hiccups on the way to market, including reimbursement difficulties that have resulted in long waiting lists for the product. But analysts are optimistic about the $373,000 product, estimating it could bring in as much as $250 million next year.

December 10: Tiny Bluebird Bio stokes optimism for CAR-T in the third type of blood cancer. Shares of gene therapy startup Bluebird Bio shot up 18% to $201.80 in a day after the company announced results from a small trial of its CAR-T in multiple myeloma. The treatment, which is being co-developed by Celgene, is different from the two previously approved CAR-Ts in that it targets a protein on myeloma cells called BCMA. The 18 patients in the trial had failed multiple previous therapies, and 17 of them responded positively to Bluebird’s CAR-T. In 10 of those patients, the cancer seemed to disappear, the companies reported at the annual meeting of the American Society of Hematology (ASH).

Early successes with CAR-T have prompted researchers around the world to see if they can apply T-cell technology to multiple cancer types, including solid tumors. Novartis and Kite are among the companies that have been working on CAR-Ts for solid tumors.

December 20: The FDA approves its 12th cancer combination treatment of the year. The rise of immuno-oncology treatments brought with it a prediction that combining multiple drug modalities might make it possible to conquer previously untreatable cancers. Several companies succeeded this year in persuading the FDA that previously approved products, including immuno-oncology treatments and targeted drugs, work better in groups than do on their own. Hence 12 new cancer combinations were approved in 2017—way up from the five combos approved in 2016.

The most recent of these approvals was awarded to Roche unit Genentech, for its combination of Perjeta, a monoclonal antibody targeted at HER-2 positive breast cancer, with the similarly targeted drug Herceptin and chemotherapy, in patients who face a high risk of recurrence. Earlier in the year, the FDA granted an accelerated approval for Keytruda combined with Eli Lilly’s Alimta and carboplatin for the first-line treatment of patients with metastatic non-squamous non-small cell lung cancer.

No doubt 2018 will bring more immuno-oncology advances—and combination treatments designed to outsmart cancer from multiple sides.

This article first appeared at https://www.forbes.com/sites/arleneweintraub/2017/12/21/five-milestones-of-2017-in-the-war-on-cancer/?ss=pharma-healthcare#15a2a7b741de

Sandeep Singh Dhillon
Unexplained medical conditions continue to baffle doctors – MIMS Malaysia
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By Hezne Ezaty Abu Hasan

Medical conditions that do not add up to a legitimate disease continue to puzzle both patients and doctors. Patients are often adamant about the seriousness and the validity of their conditions. However, without much evidence to support their claims – especially when test results turn up to be within normal limits – doctors cannot reach solid conclusions for treatments. Here are five conditions that continue to seek medical and scientific explanation to validate their status.

1. Adrenal fatigue

Exhaustion, body aches, insomnia and eye bags have been associated with adrenal fatigue; though, there is no concrete evidence to support the connection.

“Symptoms of fatigue, body aches, trouble sleeping, indigestion, and nervousness are nonspecific and could be due to a variety of other diseases, including sleep disorders, depression, irritable bowel syndrome, and thyroid disease,” Marilyn Tan, MD, an endocrinologist with Stanford Health Care and clinical assistant professor of medicine at Stanford School of Medicine told Health.

First termed in 1998, adrenal fatigue is said to have come about from the body’s response to overwhelming and continuous levels of stress – such as when a death happens or being seriously ill. The adrenal glands are unable to continue releasing cortisol for self-regulation, leading to fatigue.

However, many doctors do not agree that adrenal fatigue is a valid medical diagnosis. Instead, they think that pursuing this lead will cause other serious conditions to be overlooked.

“To attribute all symptoms to a single diagnosis of ‘adrenal fatigue’ risks missing the detection of other treatable underlying diseases,” added Dr Tan.

2. Chronic Lyme disease

Also known as post-treatment Lyme disease syndrome, chronic Lyme disease (CLD) displays symptoms such as continued fatigue, joint pains, muscle aches and sleep-impairment.

The term is commonly used to describe the 20% of patients who continue experiencing symptoms of the actual Lyme disease after being treated with a two to four weeks antibiotics course. Medical experts theorise that the lingering symptoms could be due to residual damage to tissues and the immune system that occurred during the infection.

However, doctors also diagnose patients with CLD even when they were not infected with the tick-borne illness in the first place. These patients also display similar symptoms.

Not an accepted medical diagnosis, these CLD sufferers are prescribed prolonged antibiotics to help alleviate symptoms. However, studies have shown that there can be serious complications and patients do not necessarily do better in the long run as compared to those given a placebo.

The doctors who offer such treatments “don’t typically follow the most commonly recommended treatments and the evidence-based guidelines,” said Christina Nelson, MD, medical epidemiologist for the US Centres for Disease Control and Prevention (CDC). “Most general practitioners and infectious disease physicians would not provide this type of care.”

3. Electromagnetic hypersensitivity

The World Health Organisation (WHO) does not recognise electromagnetic hypersensitivity (EHS) as a real medical condition. Sufferers of EHS claim that being exposed to electromagnetic radiation generated by electrical appliances, cell phones and Wi-Fi routers result in dermatological issues, like redness or burning sensations, and other symptoms, such as fatigue, heart palpitations and nausea.

Dr Harriet A. Hall, a medical advisor and author at Quackwatch believes that, “they are indeed suffering, and blaming their symptoms on EHS only distracts from seeking the real cause of their symptoms and helping them.”

Other medical professionals like Dr Jonathan Pham from Imperial College, London feels that there are other factors at play, “these include other environmental factors like noise and lighting as well as psychological factors such as stress and mental illness.”

The pain and symptoms should otherwise be regarded as serious until research finds proof to validate the condition.

4. Multiple chemical sensitivity
While many chemicals are proven to be detrimental to health – such as tobacco smoke and asbestos – patients believe they suffer from multiple chemical sensitivity (MCS) or idiopathic environmental intolerance due to low exposure levels of chemicals found in everyday products.

Patients claim that they suffer a wide range of symptoms such as headaches, fatigue, nausea, itching, chest pain, changes in heart rhythm, breathing problems, skin rash, diarrhoea, memory problems and mood changes. With a wide range of symptoms, there is also a wide spectrum of triggers, such as being exposed to tobacco smoke, auto exhaust, perfume, insecticide, new carpet and chlorine.

The symptoms and discomfort are real, though it may not necessarily be due to the MCS ‘disease’. Doctors believe that allergies and extreme sensitivities are at play, with depression and anxiety also being contributing factors.

“Multiple chemical sensitivity is under debate in the medical community at this time,” according to Johns Hopkins Medicine. “Some healthcare providers question whether it exists. Others acknowledge it as a medical disorder triggered by exposures to chemicals in the environment.”

5. Wilson’s syndrome

Individuals with normal thyroid levels, yet experience nonspecific signs and symptoms such as fatigue, irritability, insomnia and headaches, are often labelled with Wilson’s temperature syndrome. However, upon thyroid testing, their thyroid hormone levels are normal.

Wilson’s syndrome is also associated with low body temperature and considered to be a mild form of hypothyroidism, which Dr E. Denis Wilson – who named the syndrome after himself – claims can respond to a thyroid hormone preparation called triiodothyronine (T-3).

However, the American Thyroid Association concluded that, “there’s no scientific evidence that T-3 performs better than placebo in people with nonspecific symptoms, such as those described in Wilson’s syndrome.”

“The theory proposed to explain this condition is at odds with established facts about thyroid hormone,” it added. MIMS

The original version first appeared in https://today.mims.com/unexplained-medical-conditions-continue-to-baffle-doctors?channel=gn-policies-public-health

Sandeep Singh Dhillon
Chemotherapy-Free Cancer Treatments Move Closer To Reality – Forbes
Pharma Extra, Pharma Notables
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By Victoria Forster, CONTRIBUTOR

CAR T-cells first hit the headlines in 2012 after saving the life of a young girl in Philadelphia, Emily Whitehead, who was running out of options to treat her aggressive, relapsed leukemia. Doctors removed some of her T-cells, genetically modified them to attack a protein called CD19 on her leukemia cells and injected them into her bloodstream. Just three weeks later, she was in remission.

Although rare, it is not unheard-of for new treatments to achieve substantial early successes in one or two patients only to experience significant, sobering setbacks in larger-scale trials. This often at the very least dampens the media hype, but CAR T-cells have made consistent progress in garnering both considerable investments from pharmaceutical companies and strong results from clinical trials. Further promising results for the therapy were reported at the American Society of Hematology (ASH) conference this week for a host of blood cancers, including practically incurable multiple myeloma.

Blood cancers are often the experimental template for pioneering new cancer treatments, such as Gleevec for chronic myeloid leukemia, the first-ever FDA approved cancer therapy to target a specific protein found on cancer cells. Gleevec achieved spectacular clinical trial results before its approval in 2001 and went on to transform cancer medicine, changing a disease with a 30% five-year survival rate to one where over 80% of people survive for 10 years or more. This success is partly due to the ease of taking blood samples to monitor the effects of therapies compared to invasive biopsies and costly scans for solid tumor patients, but researchers are optimistic about the wider prospects of CAR T-cells.

“It’s an exciting time. Based on these results and recent FDA approvals in this field, there is reason to be confident that cell therapies, such as CAR T, may one day be the standard of care for hematologic malignancies as well as solid tumors,” said Reiner J. Brentjens, MD, Director of cellular therapeutics at Memorial Sloan Kettering Cancer Centre at the ASH meeting.

For tumors with currently dismal outcomes with conventional chemotherapy, this hopeful prediction can’t come true soon enough, and with almost 100 CAR T-cell clinical trials currently ongoing in the U.S. alone, including for pancreatic and brain cancers, options for patients with hard-to-treat cancers are increasing.

Many conventional chemotherapy agents kill cancer cells in a way which can crudely, but regrettably and truthfully, be described as carpet-bombing, indiscriminately affecting any cell which is dividing. CAR T-cells are the exact opposite, being engineered to target normally one very specific protein on whichever cells are in the crosshairs. In the case of many leukemias and lymphomas, this protein is CD19, present on B-cells, a type of white blood cell normally involved in the immune response when functioning correctly.

More specific therapies generally mean less toxicity for healthy tissues and fewer side-effects for patients. However, just as bacteria generate resistance to antibiotics, cancer cells are constantly evolving to evade the effects of chemotherapy. Many of the old chemotherapy drugs, for their many flaws, work in ways which make it difficult for cancer cells to evolve complete resistance as they affect processes key for survival such as DNA replication. However, the specificity of CAR T-cell therapies is, in this case, an Achilles heel. In one of the trials reported at ASH this week on refractory Non-Hodgkins Lymphoma, in a third of patients who relapsed after treatment, their cancer had evolved to simply not have the CD19 protein targeted by the CAR T-cells, rendering the therapy useless.

One of the current theories as to why this happens is that the CD19 negative cells may have been already present in the patient, just in tiny numbers. When the cells with CD19 were massacred by the CAR T-cell therapy, the cells without it no longer had any competition and thrived. So what is the solution? Make the therapy just a little bit less specific again. New studies are trialing CAR T-cells which go after two targets on B-cells, a protein named CD22 as well as CD19. It is hoped that the B-cells can’t survive if they lose both CD19 and CD22 and even if they evolve to lose one protein, they will still be susceptible to the therapy via the other.

Most CAR T-cell trials have currently been done in patients with few other options but the hope is that they will eventually be able to reduce, or even replace chemotherapy currently needed to achieve a cure, even in cancers with an excellent prognosis. For example, over 85% of children now survive leukemia long-term, but the cocktail of chemotherapies they receive come with considerable side effects, with many survivors experiencing serious health conditions later in life as a result of the treatment.

Although scientists are beginning to understand the short-term toxicities of CAR T-cells, their long-term side effects are largely an unknown and will remain so for several years. However, scientists are hopeful that CAR T-cell therapy will have fewer and less severe long-term side effects than conventional, old chemotherapies. A big ethical and moral question is how to justify replacing treatments which are undeniably very good at achieving the main goal of saving lives, with something which is currently less certain. For parents of children with leukemia who have failed conventional treatments already, the decision to try CAR T-cells is easy. For the first parents that consent to the inevitable chemotherapy-free CAR T-cell only trial, it will be a leap of faith. If all goes well, their children will be the first ever to survive leukemia without any chemotherapy treatment.

In May this year Emily, the first patient to get CAR T-cells celebrated the milestone of being five years cancer-free. Undoubtedly there are still numerous challenges to overcome before CAR T-cells become a mainstream therapy for multiple cancer types, but in five years from now, hundreds if not thousands of others will be joining Emily in this currently unique club.

The original article first appeared at https://www.forbes.com/sites/victoriaforster/2017/12/12/chemotherapy-free-cancer-treatments-move-closer-to-reality/?ss=pharma-healthcare#1486f28e6676

Sandeep Singh Dhillon
Amazon should buy these companies if it wants to get into selling drugs – CNBC News
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Christina Farr | @chrissyfarr

Amazon is considering getting into the business of selling prescriptions online.
CNBC asked five experts to pick the company that Amazon should buy first to help it compete in the $560 billion market.

Amazon should buy these companies if it wants to get into selling drugs, say experts Amazon should buy these companies if it wants to get into selling drugs, say experts. Amazon is already in a range of businesses that touch on the multitrillion medical sector, including selling surgical equipment and supplies, as well as its cloud software services which many big health-care companies use.

But if it wants to get into selling prescriptions, it might speed its time to market by making a buy-up of a company already in the space. There’s a precedent in Amazon’s $13.7 billion acquisition of grocery store chain Whole Foods earlier this year. Amazon has about $13 billion in cash and equivalents, as of September of this year.

So we asked 5 experts for their predictions on the companies that Amazon might look to acquire if it decides to move ahead with becoming an online pharmacy. Their answers have been edited for brevity.

Prediction: Premier

Scott Barclay, partner at venture fund DCVC and former vice president at e-prescription software provider Surescripts.

What is it? A group purchasing organization created to allow hospitals and other providers to pool their purchasing power to secure discounts on medical and other hospital supplies.

Why? According to Barclay, it’s a no-brainer for Amazon to buy a group purchasing organization or “GPO.” And Premier is the largest in the U.S., with a network of more than 3,750 U.S. hospitals and 130,000 other providers.

What’s in it for Amazon? “It’s a low-cost way to break into the (drug) supply chain that touches a large chunk of health care GDP,” Barclay said. “Amazon would quickly create a multibillion-dollar business without fundamentally taking on much risk or even being very innovative.”

Another benefit, according to Barclay, is that it buys Amazon time. It could pick and choose if it wants to go after more challenging opportunities like data and informatics, care provision and health insurance.

Any cons? Premier, which went public in 2013, wouldn’t come cheap — it’s currently got a market cap over $4 billion, and revenue jumped 15 percent to $1.16 billion in fiscal 2016. It has also been on a buying spree of its own of late to strengthen its market position.

Prediction: Express Scripts

Dr. Mark Frisse, Department of Biomedical Informatics at Vanderbilt University Medical Center and former chief medical officer at Express Scripts.

What is it? Express Scripts is the largest pharmacy benefits manager in the United States. These companies, known as PBMs, act as intermediaries between payers, like health insurers, and the rest of the health system.

Why? The culture fit. Amazon and ExpressScripts have a lot in common, according to Frisse. “These companies have the same business acumen, market discipline, and mastery of logistics and delivery.”

ExpressScripts could take on a job that Amazon might want to avoid, suggests Frisse. “Its team brings to the table the capabilities of managing a Byzantine and arcane process of pharmacy regulation,” he said. As Express Scripts CEO Tim Wentworth told analysts in July, it’s far more complicated than just dispensing drugs. Entering the business, “requires you to figure out how not to dispense drugs or to dispense the right drugs as much as it does to dispense them.”

Why not? It would be a massive purchase — Express Scripts has a market cap of more than $35 billion, more than twice the price Amazon paid for Whole Foods, and the company would have to borrow to take that on. It might be an easier option for Amazon to buy a small or midsized pharmacy benefits manager at a lower price, and still gain the national footprint and regulatory expertise.

Prediction: Glooko

Nina Kjellson, Canaan Partners’ biotech and health IT investor (note: Glooko is a Canaan portfolio company).

What is it? Glooko is a subscription-based diabetes management web and mobile app for patients and their health providers. It claims to have millions of users worldwide.

Why? Kjellson sees Amazon having a big impact in public health, especially in areas like obesity and diabetes. With Amazon already starting to sell medical supplies online, Kjellson sees the company carving out a big business in diabetes prescription medications and glucose meters/ strips, which is a $70 billion market and growing. “So Amazon should pick up a diabetes management platform like Glooko to have a consumer and health-care solution that ties the entire disease management ecosystem together in a great, consumer experience.”

Another bonus? As Amazon gets into the grocery business in the wake of its Whole Foods buy-up, it could consider personalized meal recommendations — a benefit for millions of people managing chronic conditions like Type 2 diabetes.

Why not? Privacy. Amazon already knows so much about its customers through their buying habits. Some users might be uncomfortable sharing their health status. Moreover, managing populations with chronic diseases is not Amazon’s core competency.

Prediction: GoodRX

Annie Lamont, managing partner at investment firm Oak HC/FT.

What is it? GoodRx offer coupons that consumers can take to the pharmacy to get discounts on prescription drugs. It claims to have lower prices than what a consumer would otherwise pay out of pocket.

Why? “It’s the most successful consumer-facing app for prescription drugs that is focused on comparing and giving the consumer the lowest cost,” said Lamont. And that’s an ideal fit for Amazon, which prides itself on transparency. GoodRx founder Doug Hirsch has also publicly stated that he would welcome Amazon’s long-rumored entry into the space.

Why not? “Valuation,” suggests Lamont. GoodRx hasn’t raised much in funding — $1.5 million in seed financing and an additional follow-on sum that hasn’t been disclosed — but has grown quickly since its 2012 launch and established itself as one of the biggest players in the space.

Any big risks? GoodRx has contracts with pharmacy benefits managers and retailers behind the scenes, explains Lamont. So there’s always a risk that they pull out, if they’re feeling threatened by Amazon.

Prediction: PillPack

Stephen Buck, co-founder of cancer-advisory site Courage Health and co-founder of GoodRx.

What is it? Pillpack is an online pharmacy start-up that delivers prescriptions by mail in personalized packets, based on when the user needs to take them.

Why? If Amazon got into the business of selling prescription drugs, PillPack seems like an obvious pick to Buck. “It’s a direct-to-consumer company that would fit nicely into Amazon’s Prime delivery service,” he said.

A good deal: PillPack also isn’t encumbered by a large retail operation, Buck said, meaning it doesn’t have a huge network of brick-and-mortar pharmacies. For that reason, it might also be “relatively cheap to buy,” he suggests, despite that it has raised more than $117 million in financing from venture investors to date.

Why not? The product might be too niche for Amazon, suggests Buck. “The whole experience including the packaging might only appeal to a certain segment of people who take multiple medications.”

Read full article here https://www.cnbc.com/2017/11/02/amazon-pharmaceutical-move-acquisition-targets.html?lipi=urn%3Ali%3Apage%3Ad_flagship3_feed%3B%2BaGvcVckQQi8j8AOTm8tcg%3D%3D

Sandeep Singh Dhillon
Amazon Is About To Disrupt The Drug Industry, But Not The Way Most Think – Forbes
Pharma Extra, Pharma Notables
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By Steve Brozak, CONTRIBUTOR

It’s now a foregone conclusion that Amazon.com will enter the healthcare sector. Every day there is another article on how Amazon is planning to dominate some new corner of the American economy. One day Amazon is taking down Grainger and Home Depot. The next it’s single-handedly taking down not only FedEx, but also UPS and the United States Postal Service. No sector seems safe as Amazon sails its ship into new waters. But those expecting Amazon to cannon ball into healthcare may need to bide their time.

Two years ago I wrote in Forbes about how Amazon’s entry into healthcare could decimate CVS and Walgreens. I think it’s still possible, but not in the way the markets and media are anticipating today. Amazon’s entry into healthcare will not be sudden. It is likely to be similar to the acquisition of Whole Foods which developed over years as Amazon evolved its strategy in home grocery delivery, one part of the incredibly valuable consumables market. It was accomplished through trial, error and recognition that Amazon needed a bricks and mortar approach to the segment that led to the Whole Foods acquisition. Sudden and complete immersion into the healthcare system as it currently exists could taint the Amazon brand and will make the company vulnerable to regulatory risk. But there are segments of the healthcare market that offer an opportunity for Amazon’s unique capabilities, and there is evidence that Amazon has been making those slow and steady moves toward healthcare.

Becoming A PBM Could Be Amazon’s Healthcare Market Entry

Pharmacy Benefit Managers are the gate-keeping middlemen of the healthcare system. PBMs administer health plans for insurance companies and employers. They manage benefits and treatment costs for these organizations. The more organizations a PBM services, the greater number of patients (or lives, in insurance lingo) under its umbrella. With more lives comes more leverage when a PBM negotiates with pharmaceutical manufacturers for drug prices.

The three largest PBMs are Express Scripts, CVS and OptumRx, covering more than 80% of insured Americans. A PBM that manages tens of millions of lives has greater purchasing and negotiating power than a standalone company with 3,000 employees, or a pension plan with 20,000 lives, or even an independent insurance plan with just a few million lives. Among a slew of other services, PBMs primarily work with their clients to construct and administer a pharmacy benefit program, which is often referred to as a drug formulary. Formularies are just the lists of drugs that are approved or that have preferred pricing for the insurance company through a PBM’s negotiations with the drug’s maker. In exchange for placing its drug on formulary, a PBM receives a preferred price and a cash rebate from the drug’s manufacturer for every prescription it processes. Your insurance plan’s formulary is a major reason why your doctor prescribes you one drug company’s medicine over a competitor’s. Being the preferred drug is the goal. PBMs share a portion of the rebate it receives with their clients (the health plans) and patients receive the benefit of a drug at a preferred price. PBMs also collect fees for transactions and services it processes for its clients.

Target and Walmart learned that merely selling pharmacies in their bricks and mortar operations or through the mail doesn’t equal profits, although a case can be made that it certainly increases foot traffic and store loyalty. Margins are incredibly thin for the kinds of drugs they sell most routinely. In fact, Target sold its in-store pharmacy business to CVS, a pharmacy and a PBM, and Walmart has partnered with McKesson to source its drugs. Becoming a full service PBM would have allowed Target and Walmart to have greater control over margin, but it wasn’t in the cards for either company. While becoming a PBM could be the key to unlocking profits for Amazon, the current political and social environment is unfriendly toward PBMs and drug makers and comes with its own risks.

Despite this, a gamble in healthcare has to happen sooner rather than later. Amazon’s primary customer is between 30 and 45 years old, and that’s a demographic that will soon be looking to fill more and more prescriptions. And if you don’t think their customers’ life cycle milestones are part of retailers’ strategic plans, just look at the pace of acquisitions around baby startups just under a decade ago. Amazon bought diapers.com while Bed Bath & Beyond acquired Buy Buy Baby. Finding an algorithm that figures out when you’re going to have a child before you even think of having one yourself is the holy grail of E-commerce. The birth of a child is a significant milestone around which there is a burst of spending to capture. Likewise, as its consumers age and continue to change their habits through online shopping, healthcare has become the next frontier. Amazon has already made an entry and is setting prices for over the counter medications (OTC). On average, its OTC products, like Tylenol, are cheaper on its website than most bricks and mortar stores. There are several theories circulating around Amazon’s entry into healthcare. Here are my thoughts on three of the most common scenarios being discussed.

Scenario 1: Amazon Acquires Or Partners With A Large PBM

One of the more popular scenarios bandied about is that Amazon may acquire a large PBM player. This is unlikely for a few reasons. Foremost, while it would allow Amazon to quickly enter the healthcare market, integrating the processes and services from a large operation into Amazon would be complicated and chaotic. As the drug pricing debate continues in the mainstream, PBMs have been painted with a big target on their backs as more light is thrown on their opaque and very misunderstood segment of the healthcare system. Just this week, Senator Lamar Alexander (R-TN) wondered out loud why PBMs even need rebates, which is the lifeblood of the industry.

It will be very difficult to recreate the frustration-free consumer experience Amazon currently offers and replicate it through healthcare services as healthcare currently exists. Therefore Amazon will want to separate any healthcare services it offers from its main brand and ease into the business. You could argue that Amazon is already easing in by selling prescription drugs on their Japanese website, perhaps a test case for an American entry (supporting the case for Scenario 3). If you think Amazon can do no wrong, remember this is the company that thought it would be a good idea to emblazon Amazon.com on the back of its Fire Phone, a complete flop. Amazon can’t afford a flameout in healthcare, and making another transformative purchase that could easily eclipse the purchase of Whole Foods so soon, while entirely possible for a company the size of Amazon, would be wholly inadvisable.

As far as partnering goes, sure, Amazon could attempt to partner with a Prime Therapeutics or an Express Scripts. As others have pointed out, Amazon has a strong history of partnering with companies, leveraging its consumer reach and logistical magic to tap into and offer lifelines to companies like Circuit City and Toys R Us. But then what happened? The companies Amazon partners with tend to go out of business as Amazon upends the market.

Scenario 2: Amazon Re-engineers The Wheel With A Smaller PBM

It’s clear that Amazon needs to either re-engineer the PBM wheel or partner with a creative player who already is. While a partnership with a conventional middle market PBM will give Amazon a good entry point in healthcare, a better route would be to partner with an even smaller PBM to really learn the business, gain valuable insights on the industry and bring the PBM model into the 21st century. There are already reports that Amazon, with its 350,000 employees, is trying to administer its own health plan internally as its own PBM. While hiring executives from industry to construct its own virtual PBM is a good way for Amazon to start, it’s still just virtual. An even better path forward would be to acquire or partner with a smaller PBM that already manages millions of lives, self adjudicates (processes its own claims) and can easily manage an additional 350,000 Amazon employees. Through the smart acquisition of a creative PBM, Amazon would learn the business model and incorporate a PBM-like service into an expanding slate of healthcare programs and service offerings.

Scenario 3: Amazon Becomes A Bricks And Mortar Pharmacy In Order To Become A Mail Order Pharmacy

Amazon is well positioned to enter the mail order pharmacy business. Most mail order services are contracted out to a handful of other pharmacies that specialize in mail order delivery. For a while, insurance companies preferred their patients to enlist in a mail order pharmacy because the pricing was competitive compared to going to CVS or Rite Aid. Over the last several years that gap has narrowed. But mail delivery is what Amazon does very well, and combining a mail delivery strategy with a bricks and mortar strategy makes an incredible amount of sense for the company, especially now that it has acquired Whole Foods.

Before acquiring Whole Foods, it never made sense for Amazon to build or to acquire a network of independent pharmacies. Since none of the Whole Foods stores have a pharmacy, Amazon has an opportunity to establish in-store pharmacies that are powered by mail order fulfillment centers. A bricks and mortar strategy should be based around having an in store pharmacist fill as few prescriptions as possible. Rather, a regional prescription fulfillment center could fill and deliver the majority of prescriptions to both the store and to the patient’s doorstep. This is not unlike the current pharmacy model whereby local bricks and mortar pharmacists fill immediately needed prescriptions in the store, while chronically needed medications are filled and delivered to the store by a regional fulfillment center for monthly pickup by the patient. A model in which Amazon combines its mail delivery capabilities with its Whole Foods bricks and mortar would begin to draw two-way traffic from the stores and onto Amazon’s website. As patients sign up and manage their medications, they would create an essential link between the virtual and bricks and mortar Amazon. Shopping for eggs at Whole Foods isn’t going to compel me to go to Amazon.com no matter how many signs Whole Foods hangs in its stores to remind me that they’re now owned by Amazon. But managing my pick up/drop off of medications at my local Whole Foods through my Amazon health portal would draw me into both. Amazon seems to understand this and has already begun to blend its online business in Whole Foods by placing its innovative pick up/return locker system in Whole Foods lobbies.

Of course, while a current generation of Americans prefer to have the personal touch of interacting with and picking up their prescriptions, the trend will soon be to have most drugs delivered by mail. I have even evaluated companies that are working on fill-on-demand drug dispensing vending machines, which may also one day make their way into Whole Foods stores (let’s call them Locker 2.0). To date the one area of true weakness for mail order pharmacy services has been providing essential prescriptions immediately, say, on the day a patient is discharged from the hospital. That’s a weakness Amazon could easily topple with its tests of Prime Now, its same-day two-hour delivery service, another incremental step as Amazon inches toward the healthcare market.

Amazon’s customer base may be young, averaging 35 years old, but they are aging and in the midst of the child-rearing cycle, which requires frequent trips to the pharmacy. Amazon’s customers will need more prescriptions for themselves and for their children. Soon an entire generation will be even more used to buying things online. Right now Amazon has announced it is preparing to make two very big decisions public. The first is whether or not it will get into healthcare, to be announced, supposedly, sometime around Thanksgiving. The second is where it will locate its second world headquarters. If Amazon wants to capture as much of the purchasing a customer can do, it will need to mature with its consumers and formally enter into the healthcare market.

And as for my prediction for Amazon HQ2: It’s Boston.