Indian drug factories erode US generic prices

MUMBAI: The most recent earnings reports across the generic drug industry have read like dispatches from the front lines of a price war.

Downtrend: A logo of Sun Pharmaceutical Industries Ltd is pictured at its research and development centre in Mumbai, India. In August, the world’s largest copycat drugmaker, Israel’s Teva Pharmaceutical Industries Ltd, slashed its dividend; US giant Mylan NV lowered its profit target; and Sun Pharmaceutical reported its first quarterly loss in at least 12 years. — Reuters

Friday, 1 September 2017

Family-owned drugmakers driving price war

This month, the world’s largest copycat drugmaker, Israel’s Teva Pharmaceutical Industries Ltd, slashed its dividend; US giant Mylan NV lowered its profit target; and India’s Sun Pharmaceutical Industries Ltd reported its first quarterly loss in at least 12 years.

The source of the pain?

At least some of it can be traced to the global ambitions of a growing constellation of family-owned drug factories in India. Their expansion is boosting competition in the US, where mergers among pharmacy chains and pricing wars between drugmakers had already been driving down the cost of generics.

“The assumption was there would be a step-down, but nobody expected it would be this bad,” said Ronny Gal, an analyst at Sanford C Bernstein & Co.

As the smaller Indian manufacturers are growing stronger, the US Food and Drug Administration is working to boost competition by handing out approvals at a record pace. The agency has said it will specifically favor generic drug applications for products that have few competitors as a way to drive down prices further.

India was already the world’s largest exporter of generic drugs, with US$16.4bil sold abroad last year. In the first half of 2017, Indian firms got about 40% of new US approvals for generics, up from 35% just a year earlier, and with a wider base of companies than ever before taking part, according to FDA data analysed by Bloomberg News.

“With more and more companies in the fray, the competition has intensified,” Pankaj Patel, chairman of Ahmedabad-based Cadila Healthcare Ltd, said in an email.

The company’s main US subsidiary has received 27 approvals this year through July, compared with eight last year. “The pure generics sphere has seen price erosion.”

India is home to about 6,000 drugmakers, according to its government’s estimates, members of a cutthroat market characterized by price controls, limited insurance levels and low patient incomes.

That makes the US look like easy pickings, according to Surajit Pal, an analyst at Prabhudas Lilladher Pvt Ltd in Mumbai.

Instead of introducing a generic product and then lowering the price when forced to, many of the Indian companies will play a far more brutal game, Pal said.

“The US business is basically icing on the cake, so they don’t mind giving you a 90% discount on the very first day,” Pal said. “The US will get cheaper products going forward.

“The US will get more competition from Indian guys.”

Thirty-two different Indian firms received US approvals to sell new generics in the first half of this year - almost double the number from two years ago.

The approvals came as India’s top 10 drugmakers grew their share of the US generics market from 14% in 2010 to about 24% today, according to Bernstein’s Gal.

Among the leaders in approvals were Hyderabad-based Aurobindo Pharma Ltd and Cadila, two of India’s biggest drugmakers who have only turned their attention to the US more recently. The companies, controlled by their founding families, are worth US$6.8bil and US$8.2bil respectively on the local stock exchange.

Smaller Indian firms that previously had little presence in the US are also seeing approvals surge.

Mumbai-based Macleods Pharmaceuticals Ltd, a closely held company that came onto the US scene in 2012 with 12 approvals, has been one of India’s most prolific filers every year since. It’s gained approvals for eight new drugs this year to treat conditions including pain, high blood pressure and depression. Ajanta Pharma Ltd, a US$1.6bil public firm that’s been operating in India since 1973, only had two US approvals to its name until 2014.

Last year, it had nine new approvals.

Or Alkem Laboratories Ltd, also operating in India for nearly fifty years.

Alkem had been chugging along with about two or three US approvals a year since 2009, but this year it’s received six.

Aurobindo, Macleods, Ajanta and Alkem didn’t respond to requests for comment.

With so many rivals in the generics space, Cadila’s pipeline needs to broader, said Patel, whose father founded the company.

“It will be crucial to look beyond pure generics at specialty products if we need to stay ahead of competition,” said Patel.

“We have a large pipeline of products which are under approval, and the attempt has been to create a judicious mix of generics, specialty and niche products.”

Successful drug makers will be ones who can develop complex technologies to deliver drugs and new formulations to create a specialty niche portfolio with less competition, he said.

Shares of Sun Pharmaceutical declined 0.9% as of 10:02 am in Mumbai. Cadila Healthcare fell 0.4%, Cipla Ltd dropped by 0.7%, Alkem Laboratories dropped 0.8% and Ajanta Pharma advanced 0.6%. The benchmark S&P BSE Sensex Index fell 0.2%.

In the US, falling prices are sweeping across the industry.

Mylan’s revenue growth has slowed in part by pressure on generic-drug prices, prompting the company to try to stave off the damage through acquisitions and new products.

Teva said it was in danger of breaching covenants on its debt amid a drop in cash flow that’s forcing it to cut jobs and exit markets. When Swiss giant Novartis AG reported earnings results in July, it said US generics sales were down 15%, driven largely by price pressure.

Overall, US generic drug prices fell 8% last quarter compared with a 4% increase in sales volume, according to Bloomberg Intelligence.

It’s not just the drugmakers that have been suffering. McKesson Corp and other major wholesalers that distribute about US$400bil worth of drugs each year cited generic pricing as a reason for their shrinking margins.

McKesson and Mylan declined to comment.

While prices of some specialty medicines have surged in recent years, such increases are harder to pull off amid greater political scrutiny and a wide-ranging US Justice Department investigation that is looking into possible price collusion in the US generics industry.

The deep discounts offered by the new Indian players to gain market share force the incumbent players to match them.

That can cut the total value of the market by as much as half, said Kumar Saurabh, an analyst at Motilal Oswal Securities Ltd

While Indian companies have drawn scrutiny from US regulators over manufacturing quality in recent years, curtailing some of the biggest players’ ability to win approvals, other firms have stepped in.— Bloomberg

http://www.thestar.com.my/business/business-news/2017/09/01/indian-drug-factories-erode-us-generic-prices/

Are stem cells really the fountain of youth?

There are many claims that stem cells possess anti-ageing properties and other secrets to youth and regeneration. However, there has not been much scientific proof demonstrating these touted abilities.

August 27, 2017 

By tasnim syakirah

Human ESCs being generated by transferring cells from a preimplantation-stage embryo into a plastic laboratory culture dish that contains a nutrient broth known as culture medium. Photo: AFP

Dr Paul Lucas, an assistant professor of orthopaedics and pathology from the New York Medical College in the United States, notes that the words “stem cells” are thrown around far too casually, and that many people assume that they are a single type of cell.

“The definition of ‘stem cell’ is an operational definition.

“That is, it describes what the cell can do, and not any particular protein or other marker it can make,” he says.

According to him, a stem cell is a cell that can:

• Differentiate into at least one phenotype (cell type), and

• Has the ability to divide, with at least one daughter cell remaining a stem cell.

What are your views on stem cells being used commercially for anti-ageing purposes? For example, there are many pills and creams made up of stem cells that are said to “reverse the ageing process”. Do you think that these are legitimate?

Lots of hype, very little biology. I have written several answers on the website Quora that address this.

Pills and creams are not legit.

The skin has a barrier called the stratum corneum that prevents bacteria from getting inside the body.

The stratum corneum will also block stem cells, which are much, much larger than bacteria, in the form of a cream.

Any stem cell will not survive in a pill with no water. And of course, any cell will not survive the hydrochloric acid in the stomach.

So there is no way “stem cells” in either a pill or a cream can get inside the body.

Even if a stem cell could get inside the body, there is very little data that any stem cell will be anti-ageing – it’s a way to separate people from their money.

There are several reasons stem cells do not counter ageing.

Stem cells are not magic. They are not magic pixie dust you can sprinkle on everything and make it be perfect.

Ageing has many causes. One of them is DNA and cellular damage.

It is thought that the various adult stem cells are the cells of origin of cancer. The data is very solid for at least hepatomas and leukaemias.

That means that stem cells can suffer mutations that alter cellular function – degrading it in some cases, and causing it to go haywire and be cancer in others.

Also, how are stem cells to be “injected”? Into each tissue? Every muscle, organ, tendon, ligament, etc?

Or are the stem cells to be injected into a vein and travel to all parts of the body?

There are two technical problems with this:

• Injecting into a vein means that most of the cells are going to be trapped in the lungs before they go out to the rest of the body, as our veins all lead first to our heart, then our lungs.

• Blood vessels are sealed tubes. Think pipes.

Just how are the stem cells supposed to exit the pipes?

This is especially true for reversing ageing in the most important organ – the brain.

The neural tissue in the brain is separated from the blood vessels by another layer of tissue called the blood-brain barrier.

Even if stem cells got out of the blood vessels in the brain, they are not going to get to the neural tissue, which is the tissue that needs to rejuvenate.

There is no way any injected stem cells are just going to magically replace all the aged cells in the body.

Stem cells are a class of undifferentiated cells that are able to differentiate into specialised cell types. Photo: 123rf.com

I read that when products use stem cells from plants, they are only using growth factors. Can you explain what this means?

Plants are very different from us. No cell from a plant is going to be able to incorporate into our tissues and act like a stem cell.

Many mammalian stem cells – particularly mesenchymal stem cells– synthesise and secrete several proteins.

Some of these proteins are “growth factors” in that they cause other cells to divide.

The claim seems to be that plant growth factors will have the same effect on human cells as they do on plant cells.

That is false.

Even some of the skincare people admit this. The following quote is from the website of a US-based skincare company that uses both human and plant stem cells: “That said, unlike human stem cells, the growth factors, cytokines and other proteins, which are the products of plant stem cells, do not have the ability to act in the same way in humans, as in plants.

“Plant stem cells communicate in a different biochemical ‘language’ that human cells do not recognise.”

What is the biggest difference between placental stem cells (PSCs) and embryonic stem cells (ESCs)?

First is the source.

ESCs are the inner cell mass of a five to seven-day-old blastocyst, which is formed after the sperm successfully fertilises the egg.

PSCs come either from the tissue of the placenta itself or from the Wharton’s jelly of the umbilical cord.

Secondly, ESCs are pluripotent, meaning they are able to differentiate into every tissue of the body. They can also form tumours in our body.

PSCs are essentially adult stem cells that have limited proliferation potential, i.e. the cell has a fixed number of times it can divide before it dies. They are multipotent, meaning that they have the ability to form more than one cell type, and do not form tumours.

Finally, stem cell injections for sports injuries (such as knee tendonitis) are common, but expensive, in Malaysia. Do you advocate this treatment over surgery and do you think this type of treatment will be less costly in the future?

Probably less costly, but no more effective.

The treatment uses mesenchymal stem cells (MSCs).

The discoverer of MSCs – Prof Dr Arnold Caplan – says they should be called “mesenchymal secreting cells”. Notice that he does not consider them stem cells!

MSCs secrete a large number of cytokines that reduce inflammation. It is inflammation that causes pain.

Aspirin, ibuprofen, and naproxen also reduce inflammation.

A “stem cell” injection with MSCs is essentially putting little aspirin factories at the site of injury.

They reduce the pain, but do little or nothing to regenerate the tissue.

For young athletes, reducing inflammation will allow the body’s healing process to work better, and thus, improve outcome.

For older patients? There is less capacity for healing.

http://www.star2.com/health/wellness/2017/08/27/are-stem-cells-really-the-fountain-of-youth/

What you should know about stem cells

The mention of stem cell research might bring to mind images of embryos in a lab used to create products meant for the skin anti-ageing business.

September 18, 2016 Living, Viewpoints

By Datuk Dr Nor Ashikin Mokhtar

The mountain flower called Edelweiss contains leontopodic acids, chlorogenic acid and other ingredients that may promote younger-looking skin.

For most of us, it seems unnatural, perhaps even unholy, to even think of using such a controversial method of defying age.

But stem cells from embryos are not the full picture, as there is more than one kind of stem cell.

Here is a breakdown of the science behind these mysterious skincare products to help you navigate this brave new world of beauty.

Human stem cells

Human stem cells are a powerful tool in science. They are unique because they have the potential to become a specialised cell, and can divide and renew themselves.

In research labs, embryonic stem cells are preferred, as they are more flexible than adult stem cells.

They usually come from four- to five-day-old embryos left over from in-vitro fertilization.

The controversy occurs because obtaining these stem cells requires the destruction of the embryo.

As it contains a potential human life, many have questioned the ethics of using embryos.

Plant stem cells

On the other hand, plant stem cells offer the same ability to self-renew and replace specific plant cells in need of repair, just like human cells.

Plant stem cells used in beauty products are cultured in pollution- and pesticide-free labs.

This technology enables scientists to have more control over the quality and quantity of anti-ageing substances the plant produces; without toxins or chemicals sneaking in from an outside source, purer ingredients are created.

Stem cells, or more precisely, the messaging molecules that are harvested from stem cells, can offer these benefits in skincare products:

• Provide antioxidant protection

• Protect skin from photo-damage by ultraviolet (UV) radiation

• Protect skin from other types of oxidative damage

• Provide anti-inflammatory benefits

• Provide stimulation to epidermal stem cells

• Increase the longevity of skin cells

Edelweiss, a mountain flower made popular by The Sound of Music, contains leontopodic acids, chlorogenic acid and other ingredients that may promote younger-looking skin.

It is said to have anti-inflammatory and cytoprotective (cell-protecting) properties. It may also prevent collagen breakdown.

Centella asiatica (also known as gotu kola, daun pegaga, Asian pennywort, pang dai woon) is native to the swamps of Madagascar, India, Sri Lanka and Indonesia.

It has been used in Ayurvedic medicine for thousands of years and supposedly has anti-ageing benefits, among other uses.

Centella asiatica (also known as Gotu kola, Daun Pegaga, Asian Pennywort, Pang Dai Woon) has been used in Ayurvedic medicine for thousands of years and supposedly has anti-ageing benefits, among other uses.

It has also been found to increase collagen in the face.

Uttwiler Spätlauber is a rare Swiss apple that supposedly has “magical” anti-ageing capabilities. However, there is not enough information about this endangered fruit to be sure of its properties.

Raspberry cell cultures are said to moisturise and lock in hydration.

Other popular sources of plant stem cells harvested for ingredients for skin care products include lilac, algae and grape seed.

The key to stem cells

Stem cells release cytokines, a type of protein, as a way to communicate with each other. This is called cell signalling.

One type of cytokine is known as growth factor, which promotes cell growth, healing and differentiation. It is important to know about cytokines because the stem cells of humans and plants do not share the same chemical make-up. Attempting to regenerate new skin cells in humans by using plant stem cells is physiologically impossible and an exercise in futility.

What can be done, however, is harvesting plant stem cells for their growth factors. Adding growth factors to stem cell products can stimulate protein production.

Stem cells are broken up when harvested, preserving the signalling molecules while discarding the rest.

So, when a product claims to contain stem cells, what it actually means is that the product contains growth factors and signalling molecules that have been extracted from the stem cells.

Whole stem cells would not be able to get through your skin because they are too large to penetrate the skin barrier.

Even individual ingredients like molecules often have difficulty getting into your skin and entering the deeper layers.

Why so expensive?

Creams and serums with stem cell-derived ingredients are also more expensive to produce, compared to going out to a field and picking some plants.

Youthful-looking skin comes at a price. The higher-end creams with stem cell-derived ingredients can set you back a few hundred, perhaps thousands of ringgit. A lot of what you pay for is really the research and development.

Other popular sources of plant stem cells harvested for ingredients for
skin care products include lilac, algae and grape seed.

Another possible reason that these serums contain hefty price tags is that they are “a novelty”. In 20 years’ time, it is possible that you may find them at your local pharmacy.

Cutting-edge skin care ingredients are exciting, but one should remain wary of the claims made about stem cell products.

This is because the evidence behind those claims is still limited, and we are just at the beginning of much more to come.

My advice is, if you can afford to experiment without a guarantee it will work, then by all means go ahead and try stem cell products.

But if you have a limited budget, wait a bit for the industry to advance and focus your attention instead on ingredients that are already proven to deliver results to your skin, like peptides, retinoids, antioxidants and anti-inflammatory ingredients.

There is a lot of promise when it comes to stem cell poducts, but some of the advertising is a bit overstated. The best advice to follow is if it sounds too good to be true, it probably is – buyers, beware.

http://www.star2.com/living/viewpoints/2016/09/18/what-you-should-know-about-stem-cells/