Novartis says glaucoma stent setback will not derail Alcon spin-off

Novartis’ eye care unit Alcon is withdrawing a surgical stent for glaucoma patients after clinical data showed it may damage the eye, but the Swiss drugmaker said the move would not affect plans to spin off the unit next year.

Novartis shares fell 0.6 percent by 0832 GMT on Wednesday, although one analyst said the company’s swift reaction should help keep it out of the crosshairs of lawyers.

As part of its voluntary withdrawal of the CyPass Micro-Stent, Alcon advised surgeons treating glaucoma patients to stop implanting the stents immediately, the company said in a statement on Wednesday.

“We believe that withdrawing the CyPass Micro-Stent from the market is in patients’ best interest and is the right thing to do,” said Alcon’s chief medical officer, Stephen Lane.

“Although we are removing the product from the market now out of an abundance of caution, we intend to partner with the FDA and other regulators to explore labeling changes that would support the reintroduction of the CyPass Micro-Stent in the future.”

The stent was designed to reduce pressure in the eye.

Based on two years of clinical data, the U.S. Food and Drug Administration had approved the CyPass Micro-Stent in July 2016 for use in conjunction with cataract surgery in adult patients with mild-to-moderate primary open-angle glaucoma.

But five-year post-surgery data showed patients experienced statistically significant endothelial cell loss compared to the group who underwent cataract surgery alone. Endothelial cells are believed to help maintain visual function.

The Alcon eye care business has highlighted the stent’s contribution to a recovery in sales. In the second quarter, Novartis said double-digit percentage growth of implantables including the CyPass stent helped drive an 8 percent surge in revenue from its surgical devices to $1.03 billion.

But a company spokesman said that CyPass sales were “immaterial” to Alcon’s total sales of $3.6 billion in the first half, and there would be no change to its target of mid-single-digit percentage sales growth in constant currencies this year.

The spokesman said the withdrawal would not have an impact on Alcon’s plans for a spin-off in the first half of 2019.

Zuercher Kantonalbank analyst Michael Nawrath estimated revenue from the stent at around $90-100 million.

Novartis’s quick move to withdraw the device after five years of patient follow-up will give little leverage to any lawyers considering potential claims against Alcon, he said.

“A withdrawal is always negative, but if you react appropriately you can avoid becoming the potential target of litigation and legal costs,” Nawrath said.

https://reut.rs/2oiBWLn

The Thyroid Diet: Is There Such a Thing?

Thyroid disease includes hypothyroidism, hyperthyroidism, and thyroid nodules, and is commonly seen in most primary care and outpatient endocrinology offices. In routine clinical practice, patients will often inquire about dietary changes they can make to treat or reverse their thyroid disease. The evidence is strongest for adequate but not excessive iodine intake to benefit thyroid health in general, as well as selenium supplementation for patients with Graves disease. Aside from these, we have sparse scientific data showing that dietary changes can significantly benefit hypo- or hyperthyroidism.

Here, we will discuss what we know about what some patients might call a “thyroid diet” and cover the most popular nutrition questions we get asked by patients with thyroid disease.

But first, a quick review.

The Most Common Thyroid Diseases

Hypothyroidism and Hashimoto Thyroiditis

Hypothyroidism affects up to 7% of the general population.^[1] Although endemic iodine deficiency is the leading cause of hypothyroidism globally, the most common etiology of hypothyroidism in the United States is Hashimoto thyroiditis, an autoimmune condition characterized by positive serum thyroid autoantibody titers and lymphocytic infiltration of the thyroid, which may lead to destruction of thyroid follicular cells, thereby increasing the risk for hypothyroidism.

Levothyroxine as thyroid hormone replacement remains one of the most commonly prescribed medications in the United States.^[2] Patients should be counseled that many foods and substances interfere with the intestinal absorption of oral levothyroxine^[3] and that taking their medication separately from mealtimes is advised.^[4]

The majority of patients with hypothyroidism experience symptomatic improvement upon treatment with thyroid hormone replacement. However, some may continue to report hypothyroid symptoms despite the achievement of biochemical euthyroidism.^[5,6] Others are dissatisfied with the current available options and seek alternative therapies.^[7,8] As such, patients may seek dietary interventions to ameliorate symptoms or reverse their hypothyroidism.

Popular interventions include supplementation with various micronutrients, vitamins, or minerals, or restricted intake of certain foods or food groups. Given the role of Hashimoto thyroiditis in the development of hypothyroidism, possible intervention to specifically decrease serum thyroid autoantibody titers is a common inquiry. Euthyroid patients with Hashimoto thyroiditis may inquire about the levelroles of iodine and selenium supplementation, as well as the potential risks of ingesting cruciferous vegetables and soy.

Hyperthyroidism

Hyperthyroidism is present in up to 1.3% of the general population.^[1] Graves disease is the leading cause of hyperthyroidism worldwide, but other etiologies include toxic nodular goiter and the hyperthyroid phase of thyroiditis. Conventional therapies for the treatment of hyperthyroidism are antithyroid medications, radioactive iodine treatment, and thyroid surgery, each with their respective potential risks and benefits.^[9]

Serum thyroid-stimulating antibodies drive the onset and course of Graves disease. Dietary iodine and selenium are micronutrients that can modify these thyroid antibody titers. Additionally, iodine status is an important consideration in individuals with thyroid nodules who are at risk for iodine-induced hyperthyroidism.

Thyroid Nodules

Thyroid nodules are often incidentally detected on radiologic imaging. Criteria based on a combination of nodule size and sonographic characteristics inform the decision to pursue a thyroid nodule fine-needle aspiration biopsy, as there is an overall risk for malignancy of only 7%-15% in all nodules.^[10] Thyroid surgery is recommended if malignancy is highly suspected or confirmed, or if benign nodules are large enough to be associated with compressive symptoms to the anterior neck. Biopsy-benign or nonsuspicious nodules are monitored by ultrasound at regular intervals. Given the chronicity of monitoring needed for benign nodules, patients will commonly seek dietary or other modalities to decrease the size of their thyroid nodules.

Specific Dietary Influences on Thyroid Health

Iodine

The production of thyroid hormone within the thyroid follicular cell requires adequate levels of circulating iodide taken in through the diet as either iodide, iodate, or organically-bound iodine. The US Recommended Dietary Allowance (RDA) for iodine is 150 µg/day in adults, and 220 µg/day and 290 µg/day in pregnant and lactating women, respectively.^[11] Common dietary sources of iodine include iodized salt, seafood (including seaweed and fish), and some breads and grains.

Iodine is not required to be labeled on food packaging; thus, dietary sources may be difficult to identify. Iodine nutrition in the United States has been adequate, but only marginally so.^[12] Although eating a regular diet should meet nutritional iodine needs, some individuals may require supplementation in order to achieve RDA goals. Individuals with restricted diets, such as vegetarians and vegans, are at higher risk for inadequate iodine intake because vegetables are not a rich source of iodine.^[13]

Some “iodine for thyroid health” tablets, which are commonly available over the counter, may contain several hundred-fold the daily recommended amount of iodine in just a single dose. Other products labeled “for thyroid support” include tablets or liquid supplements containing spirulina (a superfood derived from blue-green algae) or kelp.

When counseling patients, I stress that taking supplements with such high iodine content is unlikely to help their thyroid health, and in fact may even pose harm. In some individuals, excess iodine exposure or ingestion may induce hyperthyroidism or hypothyroidism,^[14] and chronic iodine excess may induce autoimmune thyroiditis, as highly iodinated thyroglobulin is immunogenic.^[15] Iodine-induced thyroid dysfunction is more common in those who have a history of endemic iodine deficiency or preexisting thyroid disease.^[16] For this reason, the American Thyroid Association recommends avoiding supplements containing >500 µg/day of iodine.^[17]

Goitrogens

The term “goitrogen” refers to any substance that can produce goiter, an enlargement of the thyroid gland. This is usually accomplished through effects that decrease thyroidal iodine, but goitrogenic substances can also act by inhibiting any of the other components of normal thyroid hormone production. The most common examples of dietary goitrogens are cruciferous vegetables and soy products.

Cruciferous Vegetables

Cruciferous vegetables are defined as those in the Brassica genus and include broccoli, cabbage, Brussels sprouts, kale, turnips, cauliflower, collard greens, and bok choy. They are rich in glucosinolates, compounds that produce sulforaphane and the phenethyl and indolylic isothiocyanates associated with anticancerous properties.^[18] However, glucosinolates also include the metabolite thiocyanate, which inhibits thyroid hormone synthesis.^[18] Thus, although eating cruciferous vegetables certainly has health benefits, frequent consumption of large quantities may induce or exacerbate hypothyroidism.

Data on the amount of cruciferous vegetable consumption needed to adversely affect thyroid function are limited. In a study of five euthyroid volunteers who ingested 15.2 oz of a commercial kale juice twice per day for 7 days, mean 6-hour thyroid radioiodine uptake decreased by 2.52% compared with baseline values, and serum thyroid function tests were unchanged.^[19] It would be interesting to see the results of a study with longer-term ingestion, perhaps with larger amounts of kale consumed.

In an extreme example, one case report described the development of myxedema coma in an 88-year-old Chinese woman who consumed 1.0-1.5 kg of raw bok choy daily for several months in an attempt to improve her diabetes control.^[20]

On a practical level, I tell both euthyroid and hypothyroid patients that although these data suggest that frequent intake of large amounts of cruciferous vegetables may decrease thyroid hormone production, no rigorous clinical studies exist to support the need to stop eating them. I advise a well-balanced diet that includes eating cruciferous vegetables in reasonable amounts. The problem is that we currently have very little evidence of what is “reasonable” in regard to cruciferous vegetable consumption and thyroid health.

Soy

Dietary soy products—including soy milk, tofu, soy sauce, tempeh, and miso—contain isoflavones. Because isoflavones can inhibit the action of thyroid peroxidase, which is required for thyroid hormone synthesis, it has been proposed that dietary soy intake may increase the risk for hypothyroidism in euthyroid individuals or that a higher dose of thyroid hormone replacement may be required in patients being treated for hypothyroidism.

The available literature shows that in euthyroid individuals living in iodine-replete areas, consumption of soy probably has no adverse effects on serum thyroid function.^[21] An exception is when soy-based infant formula is used for neonates with congenital hypothyroidism; an increase in dose of levothyroxine may be required to adequately address thyroid hormone needs.^[22]

I tell my adult patients that a reasonable, normal amount of soy consumption is generally safe. Furthermore, there is no reason to avoid soy if a patient with known hypothyroidism is being treated with thyroid hormone replacement.

Other Trace Minerals

The important role of iodine in thyroid health is well understood. In contrast, data on other trace minerals and their effects on thyroid status are more inconsistent.^[23]

Selenium. Selenium is a micronutrient important for thyroid hormone metabolism. The US RDA of selenium in men and nonpregnant, nonlactating women is 55 µg.^[24] The richest dietary sources of selenium are seafood and organ meats. Typical sources in the US diet are breads, grains, meat, poultry, fish, and eggs. Brazil nuts are also rich in selenium, with a single nut providing up to 90 µg.

The tolerable upper intake level for selenium is 400 µg/day.^[24] Although selenium toxicity is not commonly encountered in routine clinical practice, symptoms include nausea; nail discoloration, brittleness, and loss; hair loss; fatigue; irritability; and foul breath (often described as “garlic breath”).

Some studies have shown benefit from selenium supplementation in individuals with autoimmune thyroid disease, and low selenium levels have been associated with increased risk for goiter and thyroid nodules in European women.^[25] In areas of severe selenium deficiency, supplementation up to 100 µg/day may be beneficial.^[26] From the available evidence, however, routine selenium supplementation in individuals following unrestricted diets for the purpose of treating Graves disease,^[27,28] decreasing serum thyroid antibody titers, or maintaining normal thyroid function is mostly unsupported.

I don’t generally recommend selenium supplementation to my patients for the sole purpose of benefiting thyroid health. One exception is patients with mild Graves ophthalmopathy, in whom selenium supplementation can improve quality of life and the course of ocular disease.^[29] Supplementation in these patients is recommended by the European Thyroid Association/European Group on Graves’ Orbitopathy as a 6-month course.^[30]

Zinc, copper, and magnesium. The roles of zinc, copper, and magnesium in thyroid hormone synthesis and metabolism are even less well defined. In the US National Health and Nutrition Examination Survey (2011-2012), levels of zinc, copper, and selenium were inconsistently associated with free or total serum thyroid hormone levels,^[31] whereas a meta-analysis of eight studies suggested a relationship between levels of selenium, copper, and magnesium with thyroid cancer.^[32] Some patients may ask about these minerals and how they affect thyroid health. Given the available evidence, supplementation of these trace minerals solely for the purpose of promoting thyroid function is not generally supported.

Other Dietary Considerations for Thyroid Health

Finally, a number of other dietary factors that have much less rigorous—and in some cases, absent—scientific data are suggested to affect thyroid health. Coffee, tea, and alcohol appear to have no effect on thyroid cancer risk,^[33]although coffee decreases the absorption of oral levothyroxine in individuals being treated for hypothyroidism.^[34] The potential benefit of vitamin D as a preventive or therapeutic agent for various thyroid diseases remains unclear.^[35]

Popular in the functional medicine community are interventions to treat leaky gut syndrome, the theory of increased intestinal permeability leading to various diseases. Gluten-free diets, sugar-free diets, and probiotics are advocated for promoting thyroid health.

Although one small study demonstrated decreased serum thyroid antibody titers among 34 women who followed a gluten-free diet for 6 months,^[36]published data in the scientific literature on the effects of these interventions on thyroid health are lacking. I discuss with my patients that much remains unknown about thyroid disease and that these are areas of uncertainty in modern medicine for which continued research is still needed.

https://wb.md/2MYktGa

Cracking the sugar code: Is ‘glycome’ next big thing in health and medicine?

When you think of sugar, you probably think of the sweet, white, crystalline table sugar that you use to make cookies or sweeten your coffee. But did you know that within our body, simple sugar molecules can be connected together to create powerful structures that have recently been found to be linked to health problems, including cancer, aging and autoimmune diseases.

These long sugar chains that cover each of our cells are called glycans, and according to the National Academy of Sciences, creating a map of their location and structure will usher us into a new era of modern medicine. This is because the human glycome – the entire collection of sugars within our body – houses yet-to-be-discovered glycans with the potential to aid physicians in diagnosing and treating their patients.

Thanks to the worldwide attention garnered by the 2003 completion of the Human Genome Project, most people have heard about DNA, genomics and even proteomics – the study of proteins. But the study of glycans, also known as glycomics, is about 20 years behind that of other fields. One reason for this lag is that scientists have not developed the tools to rapidly identify glycan structures and their attachment sites on people’s cells. The “sugar coat” has been somewhat of a mystery.

Until now, that is.

While most laboratories focus on cellular or molecular research, our lab is dedicated to developing technology to rapidly characterize glycan structures and their attachment sites. Our ultimate goal is to catalog the hundreds of thousands of sugars and their locations on various cell types, and then to use this information to tailor medical therapies to each individual.

Why do we care about glycans?

In the future, it is likely that analysis of an individual’s glycans will be used to predict our risk for developing diseases like rheumatoid arthritis, cancer or even food allergies. This is because glycome alterations can be specifically tied to particular disease states. Also, biological processes like aging are linked to inflammation in our glycome. It remains to be tested if reversing these changes can help prevent disease, or even slow aging – an intriguing possibility.

Along with DNA, proteins, and fats, glycans are one of the four major macromolecules essential for life. Of these four, glycans are the final arbiters of how our cells behave.

DNA orchestrates what we look like, our capacity to think and behave, and even determines the diseases to which we are most susceptible. Within our DNA are short segments, genes, which often contain instructions for how to synthesize proteins. Proteins in turn are the “workhorses” of the cell, carrying out many of the functions necessary for life.

However, how a protein behaves often depends on what glycans are attached to it. In other words, these sugar molecules can greatly influence how our proteins do their work, and even how our cells will respond to stimuli. For example, if you change a few glycans on the outside of a cell, it might trigger that cell to migrate to a different location in our body.

The main job of glycans is to modify the proteins and fats that sit on the surface of our cells. Together, they create a thick sugar coat around the cell. If we consider the surface of the cell to be soil, then glycans would be the wonderfully diverse plant-life and foliage that sprout up and bring color and identity to the cell. In fact, if you were able to see a cell with your naked eye, it would look very fuzzy. Picture a peach with 10 times more fuzz.

Every single cell in the human body is covered with a collection of glycans which are assembled using various simple sugars like glucose, mannose, galactose, sialic acid, glucosamine and frucose as building blocks. By sensing the type of sugar coat present, our immune cells can identify other cells as friend or foe. This is because bacteria have sugars on their surfaces that are never seen on human cells – the pathogen’s sugars are sensed by the immune system and that identifies the bacteria as ‘foreign.’

Glycans label our own cells and identify them as ‘self’

The fuzz around a cell is its glycan coat. Being on the outside of our cells, glycans are the first point of contact for most cellular interactions and thus influence how our cells communicate with one another. You can also think of the glycans as a unique cellular “barcode.” Thus, a kidney cell’s fuzz will look different from an immune cell’s fuzz. But there are also similarities. In fact, the immune cells that survey our body searching for pathogens know not to attack our own “self” cells because of common features in the glycan “barcode” which are shared by all cells of our body.

In contrast, bacteria and parasites like malaria have different “sugar coats” that are not seen on human cells. When bacterial sugars are tagged as “foreign,” a person’s immune system targets the bacterium for destruction. However, some harmful bacterial pathogens like group B streptococcus, which commonly cause severe infections in babies, can avoid immune detection by impersonating human cells by carrying similar glycans as a disguise – like the wolf dressed in sheepskin.

Unfortunately some pathogens are also able to use our glycans to help them cause disease. Deadly viruses like HIV and Ebola have evolved to grab hold of specific glycans which they then “lock” onto as they infect our human cells. Therapies that either block these viruses from interacting with our glycans, or that attack virus-specific glycans may be a new avenue to treating these infections.

New research has also shown that glycans play a huge role in the development of autoimmune diseases like rheumatoid arthritis and autoimmune pancreatitis. This is not surprising since glycans directly influence the function of immune cells.

Normally, our immune cells act as our body’s “defense system,” and identify and destroy foreign invaders like harmful bacteria or viruses. But when the body mistakenly labels our own cells as the enemy and launches an internal attack on itself, autoimmunity is born. Interestingly, in such instances, it is the glycans present on the misbehaving self-attacking antibodies that will dictate the strength of the attack on the body. This abnormal immune response can even be directed against glycans. For example, the immune system can mistake “self” glycans as if they were “foreign” molecules. Our research team recently published an article that introduced the glycan theory of autoimmunity, which explains some of these relationships.

Glycans in our food can trigger immune responses

There have been many studies linking consumption of red meat with diseases like atherosclerosis and diabetes, but they have not been able to show why or how this occurs until recently. One intriguing study suggests that the culprit was a sugar with the unwieldy name, nonhuman sialic N-glycolylneuraminic acid, or Neu5Gc for short. Neu5Gc is found in all mammals except humans, because the early humans that could make Neu5Gc died from an ancient malarial parasite.

However, although we now lack the ability to produce Neu5Gc, our bodies still have the ability to incorporate it into the glycans on our cells if we obtain it by eating red meat. Once it becomes part of our cells’ glycan coat, our cells then have a “foreign” substance – Neu5Gc – surrounding them. This can trigger inflammation throughout the body because our immune system recognize Neu5Gc as “foreign” and attacks it. The chronic inflammation caused by these internal attacks can lead to heart attack, stroke and even cancer.

Our bodies synthesize tens of thousands of unique glycans, often with branching structures formed from simple sugar building blocks. Proteins or fats can also be modified by dozens of unique glycans. These countless combinations make mapping glycans a difficult task because we need a practical and efficient way to analyze hundreds of thousands of glycan patterns.

Our research team has now developed methods to rapidly and robustly monitor the human glycome. By capitalizing on engineering advancements and improvements in sample processing, our technique can monitor thousands of glycans at once, which allows us to characterize the glycans in cells from healthy controls and patients with a variety of different diseases. Our goal is to use this data to develop predictive models to help clinicians diagnose and treat all human diseases. We believe that a new wave of medical advancements will arrive as we unlock the “sugar code.”

Commentary by Emanual Maverakis, Carlito Lebrilla and Jenny Wang,  professors and research fellows in medicine and chemistry at University of California, Davis.

https://cnb.cx/2PNyvZB

Tilray sales double, thanks to more potent weed

Strong weed helped Tilray Inc. roughly double its second-quarter sales, the company said Tuesday, in the first earnings report since its July initial public offering.

Tilray stock rose 14% in after-hours trading and were up 18.5% in premarket trade Wednesday.

The Canada-based cannabis producer reported its top line grew 95% to $9.7 million, compared with $4.9 million in the year-ago quarter, driven by increased demand in Canada as well as sales to other weed companies and international sales.

The per-gram price of cannabis Tilray TLRY, +12.99%  was able to command also rose about 2.9% to $6.38 from $6.20, because the company was able to sell more high-potency weed and extracts.

“We are very pleased with our strong start to 2018,” Chief Executive Brendan Kennedy said in a statement. “Tilray is well-positioned to continue to pioneer the development of the global medical cannabis market and to become a leader in the adult-use cannabis market in Canada.”

But the company remains firmly in the red, logging net losses of $12.8 million, widening from losses of $2.4 million in the year-earlier quarter.

Typically, companies in their first public quarter report higher-than-usual stock-based compensation expenses because of vesting options, and Tilray is no different; it recorded $5.6 million in stock compensation expenses during the quarter, up from $35,000.

On the call with analysts, Tilray executives said that they expected gross margins of below 50% for the next two quarters, but that margins would rise above 50% after that.

Adjusted for items such as stock compensation and foreign exchange, the company posted losses before interest, taxes, depreciation and amortization of $4.7 million, compared with losses of $1.9 million in the year-before quarter.

Recreational marijuana will become legal in Canada starting Oct. 17. In the U.S. it remains illegal under federal law, though several states such as California, Washington, Oregon and Nevada have legalized recreational use of the drug.

Shares of the Canada-based weed maker have been on a rampage since going public at $17 in July, raising $163.6 million.

The stock has enjoyed consistent gains after Corona-maker Constellation Brands Inc. STZ, +0.93%   announced a $4 billion investment in rival Canopy Growth Corp. CGC, +1.10%  , and a report that Smirnoff-maker Diageo PLC DEO, +0.20% was eyeing a similar deal with three companies in Canada.

Tilray stock has surged more than 30% in the past five days, as the S&P 500 indexSPX, +0.14%  rose 1.2% in the same period.

Pot stocks rallied again Monday after the Canadian province of Nova Scotia announced through its government-owned liquor organization that it plans to buy 3.75 million grams of pot initially and about 15 million grams over the next year. Tilray is one of the suppliers that Nova Scotia named in its announcement.

https://on.mktw.net/2Ly29ig

Glaukos up 18% premarket on Alcon voluntary withdrawal of rival eye stent

Glaukos (NYSE:GKOS) is up 18% premarket on light volume in response to Novartis (NYSE:NVS) unit Alcon’s decision to voluntarily withdraw its CyPass MIcro-Stent from the market due to lack of efficacy. Specifically, an analysis of five-year post-cataract surgery data from the COMPASS-XT study showed little difference in endothelial cell loss in patients receiving CyPass compared to those who underwent cataract surgery only.

The device, approved by the FDA a little over two years ago, is used to reduce intraocular pressure in glaucoma patients.

Glaukos markets its iStent for the same indication.

Novartis is down 1% premarket albeit on only 400 shares.

https://bit.ly/2MEcf6o

Opiant Pharma up 73% premarket on EBS takeout of Adapt Pharma

Thinly traded nano cap Opiant Pharmaceuticals (NASDAQ:OPNT) is up 73% premarket on increased volume on the heels of Emergent BioSolutions’ announced acquisition of Adapt Pharma for up to $735M.

Adapt Pharma markets Opiant’s NARCAN Nasal Spray for the emergency treatment of opioid overdose. Opiant receives 90% of the royalties and milestone payments for the product.

Previously: Emergent Bio to acquire Adapt Pharma for up to $735M (Aug. 28)

Previously: Opiant to book $11.7M in Narcan-related income in 2017; shares up 11% premarket (Feb. 8)

https://tinyurl.com/yalanjk4

Europe ready to cash in on cheap copies of AbbVie biotech drug

U.S. drugmaker AbbVie ABBV.N faces a crunch moment in Europe in mid-October when less-expensive copies of its $18-billion-a-year biologic drug Humira – the world’s best-selling prescription medicine – hit the market.

With vast sums at stake, European healthcare administrators say they will waste no time in exploiting the situation to drive down drug bills.

“The opportunity is too big miss,” said Jatinder Harchowal, one of the coordinators of Britain’s push for greater use of cheaper biotech drug copies, known as biosimilars, and chief pharmacist at the Royal Marsden hospital.

“People are very much gearing up … I think you’ll find we are really well prepared for this,” he told Reuters.

Humira, used to treat rheumatoid arthritis, Crohn’s disease, ulcerative colitis and psoriasis, is not only a major cost-saving opportunity for healthcare services, it is also the number one target for companies manufacturing biosimilars, who hope to make a tidy profit selling their products.

Four rival companies are planning to launch Humira biosimilars and the pace of sales will be tracked closely by the wider biotechnology industry, which faces a growing copycat threat.

Because injectable biologics are made in living cells, they cannot be exact replicas of the original medicine. This makes their adoption by doctors far less certain than with generic forms of traditional “white pills” made from simple chemicals.

The conventional wisdom has been that biosimilar uptake would be slow and price discounts modest, since these products are expensive to develop and doctors may be wary about using a medicine that isn’t identical to the original.

But Europe’s recent experience with the first wave of biosimilar antibody drugs – the biggest section of the biologic market – has upended expectations, suggesting AbbVie won’t have an easy ride.

AbbVie executives have forecast Humira sales in Europe will drop around 18 to 20 percent by the end of next year, a more moderate decline than some predecessors have faced.

Indeed, the speed at which copies of Remicade and Enbrel – two rivals to Humira from Merck MRK.N and Pfizer PFE.N – have been adopted in Europe in the last three years has surprised many experts.

Roche’s ROG.S Rituxan/MabThera for blood cancer has also seen rapid sales erosion due to biosimilars.

The new competitors to Humira now see an even bigger opportunity, and the arrival of competing biosimilars from Amgen AMGN.O, Novartis’s NOVN.S generics wing Sandoz, South Korea’s Samsung Bioepis and Germany’s Boehringer Ingelheim marks an unprecedented level of rivalry.

PRICE DISCOUNTS

“We’re expecting there’ll be good competition,” Chad Pettit, head of value and access for biosimilars at Amgen, said in an interview.

He declined to go into details on pricing but said discounts for biosimilar Humira were likely to be “in the range” of other biologic drug copies already launched in Europe.

While the level of biosimilar discounts varies from country to country, Merck said they were averaging around 45 percent across Europe in the case of Remicade, one year after launch.

Britain’s Harchowal put current discounts across different biosimilars at 45 to 60 percent.

In the case of Humira, officials within Germany’s health insurance system believe the record field of contestants will add to the momentum to use the cheaper copies.

Still, analysts following AbbVie don’t expect global Humira sales to fall off a cliff just yet. In fact, revenue from the blockbuster is expected to keep climbing, driven by continuing strong U.S. demand, until U.S. biosimilars arrive in 2023.

Global Humira sales totalled $18.4 billion (14.27 billion pounds) last year, with non-U.S. sales contributing $6 billion.

And while the threat to Humira in Europe is real and imminent, there are factors that could make things somewhat different to the experience with Remicade, Enbrel and Rituxan.

For one thing, AbbVie’s reliance on its top-seller – Humira accounted for 65 percent of 2017 revenue – means it has invested heavily in preparing for this event and CEO Richard Gonzalez said in July he would compete on price “to maintain the vast majority of the line”.

AbbVie is also pushing hard to argue that patients who are stable on existing medication should not be switched for non-medical reasons, such as price.

Gonzalez said in January that the company was negotiating directly with hospitals in countries like Spain, Italy and Portugal in order to maintain its volume there.

THIS MIGHT HURT

In addition, AbbVie may try and differentiate its drug from some of the biosimilar injections that contain citrate or citric acid, which can cause pain or stinging.

This is a potential issue for Humira copies from Samsung and Sandoz, but not those from Amgen and Boehringer, which are citrate-free, according to a Reuters review of product details.

“If (AbbVie) has a formulation that has no pain and no sting, they can match price and have an advantage over a biosimilar,” said SunTrust Robinson Humphrey analyst John Boris. “That’s going to help with the longevity of the franchise.”

AbbVie said there was no connection between biosimilar launch timelines and availability of its citrate- free formulation.

Lakshmi Dharmarajan, an analyst at research group GlobalData, said uptake of biosimilar Humira might also be slowed by the fact the drug is usually self-injected at home. That could limit the role of big hospitals in forcing through biosimilar use, she said.

But pharmacist Harchowal is not so sure, pointing to the detailed planning that has gone into homecare arrangements within Britain’s National Health Service to maximize use of the best-value form of adalimumab, as Humira is called generically.

In Germany, Europe’s biggest market, the decentralized system leaves physicians free to prescribe the brand of adalimumab they deem best. But German doctors are also legally bound to observe cost efficiency and could be challenged if they simply carry on prescribing the original medicine.

Scandinavian countries already have a track record of early biosimilar adoption and have achieved some of the steepest price discounts of up to 70 percent, while France has recently stepped up its goals for their use.

France’s 2018−2022 National Health Strategy sets a goal of 80 percent biosimilar penetration by 2022 – a level that Britain has already exceeded for Remicade and Enbrel.

When it comes to Humira, NHS England told administrators earlier this year not to sign any new contracts that extend beyond Oct. 16 – the day AbbVie’s primary European patent expires.

https://bit.ly/2PNPF9G