Biologic Generics Closer to Market

Byoliveridley

Congress Seeks Compromise on Generic Drugs – New York Times

Biotech drugs, also known as biologic products, are typically proteins made by modifying the DNA of bacteria, yeast or mammal cells, and they are often given by injection or infusion. Supporters of the legislation received an unexpected boost when the chief medical officer of the Food and Drug Administration, Dr. Janet Woodcock, told Congress last month that the agency had the expertise and experience to decide what types of human and laboratory tests were needed to ensure that copies of a biotechnology drug worked as well as the original. Brand-name drug manufacturers have urged Congress to require human trials before allowing the sale of any products billed as comparable or equivalent to biotechnology medicines already on the market.

It is a complex issue, and clearly, proteins and large molecules that would not be synthesized, but “grown” are subject to larger batch by batch variation, especially when the generic company does not have access to the top-secret proprietary information that genentech, or J&J used to grow their molecule. So, some level of judgment is going to be required on the part of the FDA, which has the information from both the original, and the generic manufacturers. It looks like the FDA needs to, and is prepared to deal with each generic on a case by case basis, which is how it should be.

Protein characterization and analysis have come a long way in the last 10 years, with your fancy mass spectrometers and proteomics. It is a lot easier now to compare proteins with each other, to look for changes and differences. Mass spectrometric technology, improved electronics and huge increases in data processing and computing power make protein characterization increasingly routine. It would be up to the FDA to decide at what level of change would a protein behave so differently that its effect on humans could change significantly from the original drug, but they seem to be ready to do it.

“Some level of clinical testing should be required in all cases,” said Dr. Susan D. Desmond-Hellmann, president for product development at Genentech. Dr. Jay P. Siegel, a senior scientist at Johnson & Johnson, said: “I would never take a biologic that had not been tested in humans. The risks are too high.”

Yes, I would absolutely trust the word of the people who had the most to lose in this case, no conflict of interest here! To be fair, Dr. Siegel is understandably cautious. We have enough problems even with small molecules (think Vioxx!). But as I mentioned previously, it should be possible to come up with good enough metrics to decide when/where human re-testing is appropriate, instead of doing it always.

But Dr. Woodcock (of the FDA – inserted for context) said: “Where trials are not needed, it is of questionable ethics to repeat them. The use of human subjects for trials that are not needed is not desirable.”

People tend to forget that we’re experimenting on humans here, thanks Dr. Woodcock! Note that this is an issue where the established biologicals companies can use the safety card with impunity to protect their enormous profits. But they are not the ones who get to decide, it’s the FDA, and ultimately, Congress.

The chief lobby for makers of biotech drugs, the Biotechnology Industry Organization, strongly opposes the bill, saying it would endanger patients and kill incentives for research and innovation.

Oh really, how many times has this argument been raised, and proven to be false (see plutocracy-protectionary principle!). To believe this argument, we would have to believe that the 1984 generics law completely killed the small molecule industry. Not really, Glaxo, Pfizer, etc are still bigger and badder than ever.

Assuming a multiple sclerosis treatment costs $20,000 a year (from the article). If generics come in and there’s a 10% (low end) decline in price for the treatment, the amount saved is $2000 per patient. MS is estimated to have a prevalence rate of 0.1% in North America. So, that makes 0.3 million in the US. If half of them are on this treatment (random fudge factor), you (or your insurer) will save $300 million on one disease treatment option per year (and the biologics manufacturers will lose some portion of that). This is pretty big money, no wonder they’re throwing up roadblocks!

Similar Posts

  • | |

    Colonialism, Pharmaceutical style

    Byoliveridley

    Legal wrangle puts India’s generic drugs at risk – health – 29 January 2007 – New Scientist

    Tens of thousands of people being treated for AIDS will suffer if Swiss pharmaceutical company Novartis succeeds in changing India’s patent law, the humanitarian agency Medecins Sans Frontieres warned on Monday. Novartis is challenging a specific provision of India’s patent law that, if overturned, would see patents being granted far more widely, heavily restricting the availability of affordable generic medicines, MSF says.

    In 2000, antiretroviral (ARV) treatment cost was estimated at $10,000 per patient annually. But the availability of generic drugs produced mainly in India, allowed costs to plummet to about $70 per patient per year, Mwangi adds.

    You’ve got to love the friendly multinational arguing to make extra billions while people die. But I don’t think any Indian judge will overthrow Indian patent law. And there is a national interest  exemption built into most patent statutes, per the TRIPs agreements.

  • |

    Sugar Pills, now more effective!

    Byoliveridley

    Well, all sugar is not bad for you. Apparently, when given to you in pill form by someone wearing a white coat with a pleasant demeanour, it can cure all kinds of ills.

    It’s not that the old meds are getting weaker, drug developers say. It's as if the placebo effect is somehow getting stronger.The fact that an increasing number of medications are unable to beat sugar pills has thrown the industry into crisis. The stakes could hardly be higher. In today's economy, the fate of a long-established company can hang on the outcome of a handful of tests.

    Via Wired

    An interesting article that takes the reader through a recent history of placebos, why they seem to work better now than they used to, and tangentially, why the competitive research paradigm of the pharmaceutical industry delayed recognition, and continues to delay possible fixes and therapies.

    A few things about the placebo effect:

    1. There appears to be a physiological and neurological basis to the effect, something that can actually be turned off by deactivating the body’s natural production of opioids.
    2. This effect is triggered by various patient stimuli, including exposure to advertising, faith in the medicine, doctor bedside manner, etc. It appears that for minor ailments, these effects could be as strong as the medication prescribed.
    3. It is not short lived, the effects can linger well after consumption of sugar pills.
    4. Despite all this, the article states that we are no closer to finding the most appropriate way to administer placebos (Hmm, or are we? Read on!).

    Pharmaceutical companies conduct hundreds of clinical trials every year. They are not required to publish them in most countries, so negative results, failures, etc. which reflect badly on the company’s stock price are routinely hushed up. This means that the mounds of data that show tested drugs as no better than placebo are not accessible for research. This is one of the greatest drawbacks of competitive research paradigms, the lack of cooperation, the inefficiency that comes from duplication of negative results, and the lack of statistical power that comes from inability to use all the data available. In a milieu where knowledge = stock price, this is the logical approach, but something to note next time an Ayn Rand acolyte comes bleating to you about the beauty and perfection of the market. You might ask “What are some options to the current patent exclusivity driven regime”? My favourite economist Dean Baker of the Center for Economics and Policy Research has written extensively about the drug development process and alternatives in his excellent (and free to download) book The Conservative Nanny State, I suggest reading at least the chapter on drug development and patents!

    Anyway, back to placebos, what to do? How to administer sugar pills in a quasi-official setting for minor ailments. It’s almost like you need a parallel paradigm of medicine that dispenses sugar pills that did not have to go through double blind randomised clinical trials. it would help if this paradigm uses vaguely scientific terminology while doing very little harm. It would work in conjunction with the conventional approach, not in competition so there is little danger of people taking sugar pills for malaria!

    I give you, Homeopathy!!! This blog(ger) is no stranger to this wonderful form of medicine, involving concepts such as the memory of water, similars, dilution, etc. When I wrote about homeopathy last year, it was more in relation to the psychological aspects of my experience with it. I (and I assume you did not click through to read!) wrote about my parents’ great and enduring relationship with their homeopath, and the benefits it brought them. Back in India this time around, it was suggested that I take some homeopathy for a cold I was developing, which I did (yum, sugar!). The cold went away in a few days 🙂 There was some swine flu medicine being passed around as well (I did not partake), which worked too, nobody at home got swine flu 🙂

    So, how to make it work? It already works in India because belief in the efficacy of homeopathy is well established. As long as the homeopath is well qualified in basic diagnosis, and crucially, knows when to punt the patient into conventional therapy, the system works to a certain extent. But what about a society with no such foundation? Do you go to a clinic with both an allopath and a homeopath, and if your ailment is one where placebo works about as well, let the homeopath make some well diluted similars for you to consume? How to settle turf wars? Would it be better for the allopath to feign develop an expertise in homeopathy and make that work for her in treating the patient? Would they apply the most important lessons in homeopathic treatment, Listen, Empathise, Soothe?

    I don’t know. It is not my nature to believe in sugar pills, faith, or advertising. So it is hard for me to say what would work. But given that sugar pills work well, it is vital for society to find a way.

  • | |

    Indian firms push down global vaccine prices – Lessons for Canada

    Byoliveridley

    Cheaper vaccines from India are forcing global giants to slash prices. GSK announced its rotavirus vaccines at $2.50 per dose — or $5 to fully immunise a child — in response to a current tender administered by UNICEF.The offer is a 67% reduction in the current lowest available public price.

    Hindustan Times

    This is good news for many reasons. Preventable diseases kill over a million people every year, and one of the biggest factors in getting vaccinated is cost. India’s healthcare spending was estimated at US$ 40 billion in 2008, going up to 300+ billion in 2023. Forty billion is less than $40 per person, so saving 7-8 dollars on vaccinations alone for every one of the 26 million children born every year is a huge deal.

    Development costs of vaccines and drugs are high and success is often uncertain. Pharmaceutical companies have used this to justify government enforced monopolies and per dose prices that are sometimes a 1000 times higher than the incremental cost of production. While this makes for good profits, it means severe lack of access in India, many African countries, and many excess deaths that could have been prevented. For years, India had what was called a process patent, not a product patent, which meant that if you could make a drug with a slightly different process, it would not get patent protection any more. How did this help India?

    1. Affordable drugs – Indian companies could make and sell drugs at a fraction of the cost without paying for drug development.

    2. Pharmaceutical Industry – This enabled the industry to grow and mature.

    Of course, this also meant that India was considered an outlaw, and Indian pharmaceutical industry came under great pressure from the WTO to tighten patent laws, which it did. At the time, the concern (rightly) was that tightening patent restrictions would harm India’s pharmaceutical industry and reduce access to drugs. Has this come to pass? In some ways, yes. But the Indian pharmaceutical industry has also matured, and with government help, has been able to do its own development, clinical trials and production (which it was always good at). The focus on tropical diseases like rotavirus also means that US, European Companies, which have since moved away to treating chronic conditions like high cholesterol, erectile dysfunction, etc., have much more competition in the tropical diseases area and cannot charge premium prices to poor people any more.

    So dear Canada, while you are negotiating with Europe about “free trade”, and trying to give European companies much greater patent protection for their drugs, know that this will very surely raise costs in the short term. Two important questions:

    1. Will Canada’s drug companies benefit?

    2. Will Canada’s consumers benefit?

    Um, let’s take a look at Canada’s top 10 in 2009:

     

    Rank Leading Companies Country Market Share (%)
    1 Pfizer US 13.4
    2 Apotex Canada 7
    3 AstraZeneca UK 6.6
    9 Merck US 6
    4 Johnson & Johnson US 5.3
    6 Novopharm (Teva) Israel 4.2
    7 Novartis Switzerland 4
    5 GlaxoSmithKline UK 4
    8 Abbott US 3.9
    10 Roche Switzerland 3.1
    Source: IMS Health

    There is one Canadian company in the top 10, and four European companies. Our pharmaceutical industry is not well positioned to be independent, or work to reduce Canadian drug prices, especially if laws strengthening patent protections for European companies come into effect. This will serve to weaken Apotex, and Canada does not have a big independent pharmaceutical company network born out of years of “isolation” to take advantage of any competition, or competitive advantages. So, while patent “reform” seems to not have hurt Indian industry as much as feared, it sure will hurt Canadian consumers.

     

  • |

    An off patent miracle cancer cure?

    Byoliveridley

    Interesting news coming out of Canada from a Dr. Anselm at the University of Alberta about a well known chemical dichloroacetic acid (like vinegar with two chlorines!).

    Cheap, safe drug kills most cancers – health – 17 January 2007 – New Scientist

    It sounds almost too good to be true: a cheap and simple drug that kills almost all cancers by switching off their “immortality”. The drug, dichloroacetate (DCA), has already been used for years to treat rare metabolic disorders and so is known to be relatively safe.

    It also has no patent, meaning it could be manufactured for a fraction of the cost of newly developed drugs.

    Here’s the PubMed citation for the article, filled with biology I will have no hope of understanding! I read the press release on sciencedaily a few days back and did a little background digging.

    A clinical trial conducted by Colombia University studying the effects of dichloroacetate on MELAs (stroke like symptoms) was halted early because everyone taking the medication showed significant effects of neural toxicity. This study was commented on by Dr. Anselm who theorized that the effect could be caused by a specific gene mutation not seen in a lot of the patients he works with.

    So, there is some reason for caution on this wonder drug, it may be toxic at certain doses to certain people. Most chemotherapetic drugs are horrendously toxic too. But if this is not a concern, Dr Anselm, meet Sunil Shaunak and his wonderful proposal to setup an alternative pipeline for drug approval that does not involve big/small pharma. I Am sure between Bill Gates, or George Soros, a few million bucks can be rustled up for a cancer cure.

  • Doctors Take Bribes to Prescribe Drugs

    Byoliveridley

    This is the headline I would have used on this story. An incentive scheme to use a paticular product in a situation like this is a bribe.

    Doctors Reap Millions for Anemia Drugs – New York Times

    Two of the world’s largest drug companies are paying hundreds of millions of dollars to doctors every year in return for giving their patients anemia medicines, which regulators now say may be unsafe at commonly used doses.

    The payments are legal, but very few people outside of the doctors who receive them are aware of their size. Critics, including prominent cancer and kidney doctors, say the payments give physicians an incentive to prescribe the medicines at levels that might increase patients’ risks of heart attacks or strokes.

    Industry analysts estimate that such payments — to cancer doctors and the other big users of the drugs, kidney dialysis centers — total hundreds of millions of dollars a year and are an important source of profit for doctors and the centers. The payments have risen over the last several years, as the makers of the drugs, Amgen and Johnson & Johnson, compete for market share and try to expand the overall business.

    So how does this kickback scheme work?

    Federal laws bar drug companies from paying doctors to prescribe medicines that are given in pill form and purchased by patients from pharmacies. But companies can rebate part of the price that doctors pay for drugs, like the anemia medicines, which they dispense in their offices as part of treatment. The anemia drugs are injected or given intravenously in physicians’ offices or dialysis centers. Doctors receive the rebates after they buy the drugs from the companies. But they also receive reimbursement from Medicare or private insurers for the drugs, often at a markup over the doctors’ purchase price.

    Medicare has changed its payment structure since 2003 to reduce the markup, but private insurers still often pay more. Combined with those insurance reimbursements, the rebates enable many doctors to profit substantially on the medicines they buy and then give to patients.

    The rebates are related to the amount of drugs that doctors buy, and physicians that agree to use one company’s drugs exclusively typically receive higher rebates.

    Wow, that’s a scheme that would be illegal in almost any situation. I buy 10 widgets from the manufacturer for $100. The manufacturer then gives me $50 in “rebate”. I charge the person on whose behalf I am buying these widgets $200 even though I am not supposed to make a profit on this transaction, and pocket $150 from a transaction. I also promise to use more of this widget, on people who may or may not need it, but on whom I have such a knowledge gap and power gap that I know that they will use it whether it is actually good for them or not. I also promise not to use a competitor product even though I know that there are cases where one product will be better than the other. Well, who pays, all of us in increased health insurance premiums and healthcare costs so a bunch of rich doctors can drive their Range Rovers around.

    The USA is no different from India when it comes to schemes like this. The money involved is greater, and somehow, this is not called a bribe by the media.

    What does the pharma spokesperson have to say?

    Johnson & Johnson said yesterday in a statement that its rebates were not intended to induce doctors to use more medicine. Instead, the rebates “reflect intense competition” in the market for the drugs, the company said.

    Amgen said that rebates were a normal commercial practice and that it had always properly promoted its drugs.

    Yes, it’s competitive out there, and to ensure that our product gets used, we will bribe people.

    The “consumer” is the person who pays for the product or service. The “consumer” here is the end user, the patient. The patient does not get the rebate, instead having to pay high prices so doctors can add to their six figure incomes. Nice!

  • | |

    What can the U.S learn from homeopathy?

    Byoliveridley

    Homeopathy was all around me growing up in India, so I read this article with interest as it jogged many memories of visiting the family homeopath with my parents.

    Faith Healing with Homeopathy — In These Times

    Homeopathy rests on three unproven tenets: First, “Like treats like.” Because arsenic causes shortness of breath, for example, homeopaths prescribe its “spirit” to treat diseases such as asthma. Second, the arsenic or other active ingredient is diluted in water and then that dilution is diluted again and so on, dozens of times, guaranteeing—for better and worse—that even if the dose has no therapeutic value, it does no harm. And third, the potion is shaken vigorously so that it retains a “memory” of the allegedly curative ingredient, a spirit-like essence that revives the body’s “vital force.”

    Fooey, the description of the science is hilariously pseudoscientific, but homeopathy is no laughing matter in India. It is estimated to be a Rs. 250 Crore (that is 2.5 billion rupees or about $58 million) industry as of 2002-2003.  I do not think this includes doctors and clinics. This website lists 158 colleges in India offering the  valid (it is like an MD!) degree of Bachelor of Homeopathic Medicine and Surgery, or BHMS. My parents swear by it, most of my family living in India has either visited, or regularly visit one. It is hugely popular for hepatitis and liver disease, more so than conventional medicine in India.

    What’s the deal? Why is it so popular? I think Terry Allen is on the right track, this sentence here, buried in the middle, hits the nail on the head…

    Part of the effect comes from the ritual of consultation with a practitioner who treats the patient like a person rather than a body part on an assembly line.

    Allen does not quite grasp the significance of this sentence and tracks away into placebo effects and evil pharma. But here’s the deal: A lot of Indians (who can afford $4-$5 consultation fee) visit their homeopath every month. When I tagged along with my parents, we would go on a Sunday afternoon at 2 PM to this homeopath’s office, which was a wing of his house (a big house, I might add!). It was a relaxed and leisurely time, he spent 10-15 minutes with each of us (yes, my parents made me!) talking about the previous month, what we were up to, how stressed we’d been, how our ailments from the previous month were doing, had we noticed any changes to our health over the month, etc. We would be interrupted occasionally by his little kid, or his assistant relaying a message from his wife, it was as far removed from a doctor’s visit as possible. And yes, he would take your blood pressure, run simple blood tests, etc. At the end of it, he would give you little sugar pills/sugar coated powder formulations to take home. The formulations were individually dosed, it was all categorized and labeled for you.

    This is like having a mini physical every month. Surely, just the act of talking to someone made you feel better, the act of ritually opening up little packets of “medicine” and following detailed instructions for 5 days helped, surely the homely and relaxing atmosphere of visiting a family friend helped, I don’t know.

    Metrics? both my parents occasionally had their hypertension treated with homeopathy. This worked as long as they were borderline, and simple stress management would get the numbers down. This doctor was/is very good at stress management because he talked calmly, yet firmly, he would listen and tease their little everyday stressors out of them and that was probably good for a 10 point reduction. But I remember the homeopath sending mom off to a doctor for a more conventional treatment regimen as soon as she hit 160.

    It never ever worked for me because I was way too sceptical to buy into the process, so I would not listen, or relax enough to talk. I would take my pills, but it would make absolutely no difference whatsoever. Of course, he was trying to treat me for severe sinus related issues probably brought on by pollution, and by sleepless nights spent on a beach looking for turtles!

    I am sure that for every good homeopath, there were two bad ones who just handed out pills of sugar. But my parents’ homeopath was, and continues to be part Dr. Phil, part candyman, part cheerleader!

    Homeopathy probably “works” because it makes people take the time to think about their life and what’s ailing them. It’s a lesson that American primary care providers could do well to learn.