DRUG DEVELOPMENT DECONSTRUCTOR MANIFESTO: : “Tell me how you read and I'll tell you who you are.” ― Martin Heidegger
Saturday, June 30, 2012
Amylin is sold... Too cheep?
From here.
Three months after rumors surfaced that Bristol-Myers Squibb was pursuing Amylin Pharmaceuticals, a deal has been struck. The big drugmaker has agreed to pay $5.3 billion – and assume $1.7 billion in debt – in hopes of strengthening its position in the competitive diabetes market. And in connection with the deal, which effectively amounts to $7 billion, AstraZeneca will pay $3.4 billion to Bristol-Myers to expand their existing diabetes partnership.
Well, I like this numbers... However it is very hard to imagine how anybody could spend them...
Friday, June 29, 2012
News can cause mental diabetes.
Very unexpected but true point of view:
News is to the mind what sugar is to the body We are so well informed and yet we know so little. Why? We are in this sad condition because 200 years ago we invented a toxic form of knowledge called “news.” The time has come to recognize the detrimental effects that news has on individuals and societies, and to take the necessary steps to shield yourself from its dangers. At core, human beings are cavemen in suits and dresses. Our brains are optimized for our original hunter-gatherer environment where we lived in small bands of 25 to 100 individuals with limited sources of food and information. Our brains (and our bodies) now live in a world that is the opposite of what we are designed to handle. This leads to great risk and to inappropriate, outright dangerous behavior. In the past few decades, the fortunate among us have recognized the hazards of living with an overabundance of food (obesity, diabetes) and have started to shift our diets. But most of us do not yet understand that news is to the mind what sugar is to the body. News is easy to digest. The media feeds us small bites of trivial matter, tidbits that don’t really concern our lives and don’t require thinking. That’s why we experience almost no saturation. Unlike reading books and long, deep magazine articles (which requires thinking), we can swallow limitless quantities of news flashes, like bright-colored candies for the mind. Today, we have reached the same point in relation to information overload that we faced 20 years ago in regard to food intake. We are beginning to recognize how toxic news can be and we are learning to take the first steps toward an information diet. This is my attempt to clarify the toxic dangers of news – and to recommend some ways to deal with it.
Targeted failure. Again.
It looks like we have a good (or bad) tradition that once a month a new experimental targeted medicinal product fails in clinical trials. Very often these drugs are very complicated biologicals with very “sexy” story why they actually “are best and should be successful”. This time we have blisibimod which is:
Blisibimod (also known as A-623, formerly AMG 623) is a selective antagonist of B-cell activating factor (BAFF, also known as B-lymphocyte stimulator or BLyS), being developed by Anthera Pharmaceuticals as a treatment for systemic lupus erythematosus. It is currently under active investigation in clinical trials.
MechanismBlisibimod is a fusion protein consisting of four BAFF binding domains fused to the N-terminus of the fragment crystallizable region (Fc) of a human antibody.
BAFF is involved in B-cell survival, activation, and differentiation. Elevated levels of BAFF have been associated with several B-cell mediated autoimmune diseases, including systemic lupus erythematosus, lupus nephritis, rheumatoid arthritis, multiple sclerosis, Sjögren’s syndrome, Graves’ disease, and Hashimoto's thyroiditis. Blisibimod binds to BAFF and inhibits interaction with BAFF receptors, thus decreasing B-cell survival and proliferation throughout the body. Improvements in disease activity have been observed in patients with systemic lupus erythematosus and rheumatoid arthritis following treatment with BAFF inhibitors in clinical trials.
And what a failure:
NEW YORK (AP) -- Shares of Anthera Pharmaceuticals Inc. plummeted Thursday after the company said its experimental lupus treatment blisibimod failed in a clinical trial, and changed its development plans for the drug.
THE SPARK: Anthera said blisibimod did not meet its goals in the study, because two of the three doses it studies were not effective when compared to a placebo. The company said patients who received 200 milligrams of blisibimod per week experienced improvement, but those who received 100 milligrams per week or 200 milligrams per month did not do significantly better than patients who were given a dummy shot.
Well, targeted failure...
Thursday, June 28, 2012
India: 348 drugs for free!
From here. The indian goverment should be communists?
India has announced that medicines will be available free to everyone who needs them from October, and that 100 crore rupees (1 billion rupees, or around $17.5 million) has been received from the Planning Commission to finance the supply of free medicines for 2012-13.
The government will fund 75% of the costs of the scheme, which are expected to total 28,560 crore rupees over five years, say government spokesmen, who describe the initiative as "game-changing."
The Office of Prime Minister Manmohan Singh has asked the Health Ministry to set up a new central procurement agency for bulk drug-buying as quickly as possible, and individual states have been sent the 348-product 2011 National List of Essential Medicines for use as reference. The states, which will finance 25% of the programme, will also be required to establish their own essential drugs lists (EDL), based on their particular local needs
Under the programme, states will procure medicines through an open tender, directly from manufacturers and importers. Firms applying for the tenders will be required to have Good Manufacturing Practice (GMP) compliance certificates, no-conviction certificates and specified annual turnover, and the products they supply for the scheme must have "not for sale" printed on their packaging, say government officials.
Also, it will be made mandatory for all doctors working in the public sector to prescribe generics only
Well, I think that Big Pharma somehow will stop this communistic altruistic behaviour! Sooner or later!
Wednesday, June 27, 2012
Tuesday, June 26, 2012
Masterpiece of the day. Fermat's Last Theorem
In number theory, Fermat's Last Theorem states that no three positive integers a, b, and c can satisfy the equation an + bn = cn for any integer value of n greater than two.
Amylin execs purportedly lied to investors... Surprised?!
From here.
In a damning disclosure, an FDA official charges that Amylin Pharmaceuticals concealed a study that raised heart safety concerns about its Byetta diabetes drug and then hindered agency access to the data when it was discovered, TheStreet reports, citing newly released FDA documents. And later, Amylin execs purportedly lied to investors by failing to disclose that the Byetta study played a key role in an agency decision to reject the Bydureon follow-up treatment.
The Bydureon review and approval was a “long and complicated process, in part due to Amylin’s withholding of information on Byetta that FDA deemed to be important to its evaluation of the safety and effectiveness of Bydureon,” according to a January 2012 memo written by Mary Parks, division director of the FDA office that is responsible for diabetes drugs, TheStreet writes in its expose.
Well, I have found in this story only one very interesting issue namely that Byetta and Bydureon have definite cardiac toxicity. The fact that some pharmaceutical company is not behaving ehtical and try to lie – is it strange and worth of our attention? It should be expected!
Monday, June 25, 2012
Sunday, June 24, 2012
Ron Paul. Syria.
Clever man but he does not understand that the only reason for the war is to maintain the world economy afloat...
Saturday, June 23, 2012
Friday, June 22, 2012
Another cure from cancer. Again! (Post No 7)
This time we are talking about new drug delivery system based on doxorubicin designed for treatment of liver cancer:
The company, with a market valuation of only about $70 million and all of 16 employees, is not trying to reinvent the wheel. But by placing a very old cancer drug - the chemotherapy doxorubicin - into a new delivery method and adding heat, Celsion believes it has a recipe for success that can address a large need in cancer.
About 750,000 new cases of liver cancer are diagnosed each year. The World Health Organization has predicted that by 2020 liver cancer will surpass lung as the No. 1 cancer worldwide.
ThermoDox is intended for liver cancer patients not eligible for resection surgery.
Tardugno was not ready to predict multiple billions in annual sales just yet and noted that all, of course, depends on positive data from its pivotal late stage trial.
For sure, billions in sales! Well, why not? I see a positive issue here that we have a novel approach which differs from the crazy modern HTS. I think that the company has good chances for success.
Thursday, June 21, 2012
Quote of the day. Khazin about european project
Is it dirty propagnda?
«Западный» проект, как и всякий глобальный проект, имеет проектную элиту, цель и задача которой - сохранить проект в целостности и идеологической преемственности. Да, какие-то небольшие изменения в идеологии возможны, но в целом - она должна сохраняться. А это значит, что вся система выстраивания этой элиты (в которую, в качестве составных частей, входят и политические элиты базовых стран «Западного» проекта, и мировая финансовая элита) должна быть построена на обязательной и постоянной «присяге на верность» . Как только присяга нарушается, соответствующий персонаж из элиты выкидывается.
ABC of business clichés
Very interesting and useful knowledge in order to really understand the messages of counterparts
I like especially these statements:
It’s about synergies/1 + 1 = 3 = I don’t get the math either, but it sounds like more and more is better, right?
- We need to monetize/strategize/analyze/incentivize = When in doubt, stick “-ize” on the end of a word and say we’ve got to do this and 9 out of 10 times, it will sound action-oriented.
- It was a perfect storm = We really screwed up but we’re going to blame a bunch of factors that are out of our hands (especially weather)
- At the end of the day…. = OK, enough talking back and forth, we’re going to do what I want to do
- Don’t leave money on the table = Be as greedy with them as possible
- Hope is not a strategy = I don’t have a strategy, but this makes it sound like I’m above people who also don’t have a strategy
- This time it’s different because… = Don’t wait for the explanation… simply run for the hills.
- We want this to move up and to the right = I failed high school algebra but someone said this means we’ll be making a lot of money if this happens
Wednesday, June 20, 2012
Decision-making process and data toxicity etc
Absolutely amazing statement of Taleb in the manner of Dugin or Pereslegin – very counter-intuitive but really-bad-true!
… doctors need to justify their salaries and prove to themselves that they have some work ethics, something “doing nothing” doesn’t satisfy. Indeed at the time of writing the personal doctor or the late singer Michael Jackson is being sued for something that is equivalent to overintervention-to-stifle-antifragility (but it will take the law courts a while before they become familiar with the concept). Conceivably, the same happened to Elvis Prestley. So with overmedicated politicians and heads of state.
…
There is a biological story with information. I have been repeating that in a natural environment, a stressor is information. So too much information would be too much stress, exceeding the threshold of antifragility. In medicine, we are discovering the healing powers of fasting, as the avoidance of too much hormonal rushes that come with the ingestion of food. Hormones convey information to the different parts of our system and too much of it confuses our biology. Here again, as with the story of the news received at too high a frequency, too much information becomes harmful.
…
In business and economic decision-making, data causes severe side effects —data is now plentiful thanks to connectivity; and the share of spuriousness in the data increases as one gets more immersed into it. A not well discussed property of data: it is toxic in large quantities —even in moderate quantities.
Well, too much data is toxic... Say it to the bioinformatic scientists :)
Mabs will fail again?
I have written a lot of times that, by the experience, targeted medicines developed in accordance to the modern paradigm are very ineffective. I will not go into details of this fact again and again (just see here and here). A new possible failure is close: Institutional investors doubt that treatments for Alzheimer's disease being developed by Pfizer Inc and Eli Lilly will achieve the main goals of their ongoing late-stage trials.
This time we are talking about the following mAbs: solanesumab and bapineuzumab:
Results from the survey of 146 investors were released late on Tuesday by Mark Schoenebaum, a pharmaceutical analyst for the investment research services group. Wall Street is eagerly awaiting results of the trials and expects huge potential sales if either of the medicines proves able to arrest the progression of the memory-robbing disease.
The survey responders, on average, gave solanezumab only a 14 percent chance of meeting all the primary goals of its two Phase III studies, compared with an average 21 percent probability for the two big trials of bapineuzumab, Schoenebaum said.
Likewise, responders cite an average 15 percent probability of the Lilly's drug winning approval from the U.S. Food and Drug Administration sometime in the next two years, compared with 29 percent odds for bapineuzumab.
I do not know do the investors really understand the reason of failure or they just do not believe in the companies developing these medicines. I think that more people will come to conclusion very soon that mAbs are not so sexy as Big Pharma is painting.
Then I am waiting for the failure with this project.
Then I am waiting for the failure with this project.
Quote of the day. Female logic
From here.
1.Сегодня утром пока красилась, 5 раз в обморок падала от своей красоты…
2.Когда уже научатся проводить свет в женские сумки?! Очень надо!!!
3.Женщина должна быть любимой, счастливой, красивой! А больше она никому ничего не должна.
4.У женщин не бывает лишнего веса… Это дополнительные места для поцелуев…
5.Мне бы колечко… А то пальчики мерзнут…
6.Хотела стать самой лучшей — не дали… Хотела стать самой худшей — не смогла… Придется остаться неповторимой…
7.Сижу на трёх диетах — двумя не наедаюсь!
8.Он ест — я готовлю, он носит — я стираю, он разбрасывает — я убираю. И что бы я без него делала-то…
9.Женская народная забава: сама придумала, сама обиделась.
10.Я как шампанское, могу быть игривой, а могу и в голову дать…
11.Так хочется быть слабой женщиной, но, как назло, то кони скачут, то избы горят…
12.Если кто-то из мужчин звонит вам, когда он пьян — цените это. Вы очень дороги этому человеку.
13.Самый лучший секс с тем, с кем хорошо и без секса.
14.Женщина должна принадлежать тому мужчине, который решит все её проблемы, а не создаст новые.
15.В принципе, женщина может и промолчать, но дело в том, что у женщины нет такого принципа.
16.Я как кабриолет, такая классная, а крыши нет!..
17.У меня муж гулять начал: каждый день по барам, по кабакам, по ресторанам. Меня ищет!
18.Проснулась, умылась, нарядилась, улыбнулась и пошла украшать мир…
19.Я люблю апельсиновый сок, а мои подружки — персиковый… Но когда мы встречаемся — мы пьём водку…
20.Боже, дай мудрости, чтобы понять мужчину. Дай любви, чтобы прощать его. Терпенья — чтобы выдержать его характер. Только сил не давай, а то убью его нафиг.
2.Когда уже научатся проводить свет в женские сумки?! Очень надо!!!
3.Женщина должна быть любимой, счастливой, красивой! А больше она никому ничего не должна.
4.У женщин не бывает лишнего веса… Это дополнительные места для поцелуев…
5.Мне бы колечко… А то пальчики мерзнут…
6.Хотела стать самой лучшей — не дали… Хотела стать самой худшей — не смогла… Придется остаться неповторимой…
7.Сижу на трёх диетах — двумя не наедаюсь!
8.Он ест — я готовлю, он носит — я стираю, он разбрасывает — я убираю. И что бы я без него делала-то…
9.Женская народная забава: сама придумала, сама обиделась.
10.Я как шампанское, могу быть игривой, а могу и в голову дать…
11.Так хочется быть слабой женщиной, но, как назло, то кони скачут, то избы горят…
12.Если кто-то из мужчин звонит вам, когда он пьян — цените это. Вы очень дороги этому человеку.
13.Самый лучший секс с тем, с кем хорошо и без секса.
14.Женщина должна принадлежать тому мужчине, который решит все её проблемы, а не создаст новые.
15.В принципе, женщина может и промолчать, но дело в том, что у женщины нет такого принципа.
16.Я как кабриолет, такая классная, а крыши нет!..
17.У меня муж гулять начал: каждый день по барам, по кабакам, по ресторанам. Меня ищет!
18.Проснулась, умылась, нарядилась, улыбнулась и пошла украшать мир…
19.Я люблю апельсиновый сок, а мои подружки — персиковый… Но когда мы встречаемся — мы пьём водку…
20.Боже, дай мудрости, чтобы понять мужчину. Дай любви, чтобы прощать его. Терпенья — чтобы выдержать его характер. Только сил не давай, а то убью его нафиг.
Tuesday, June 19, 2012
Diabetes type 2: juicy bite for Big Pharma. Part 3
From an advertisement (Metabolic Disorders Therapeutics Market to 2017), very interesting numbers for diabetes and obesity:
The global diabetes diseased population in 2010 was estimated at 58 million, while in the same year, the obesity diseased population was estimated at 203 million and the dyslipidemia diseased population was estimated at 259.1 million. Nevertheless, in 2010, the diabetes market accounted for 95% of the global metabolic disorders therapeutics market. The major reason for the significant market share related to diabetes is the failure of anti-obesity drugs in proving their efficacy and safety. Other existing drugs in the market are also associated with severe side effects, resulting in poor utilization by obesity patients. The diabetes market has witnessed product failures as well.
The global metabolic disorders therapeutics market is attractive despite product failures. The major factor driving the growth of the market is the rising incidence of obesity and the diabetes diseased population in key markets such as the US, the UK and Germany. It is forecasted that the metabolic disorders therapeutics market will grow at a CAGR (Compound Annual Growth Rate) of 3.1% between 2010 and 2017. The market would be primarily driven by the rising prevalence rates and the market entry of new products.
Well, not bad – the market is really huge...
The metabolic disorders therapeutics mergers and acquisition (M&A) landscape is moderately active, as only a few major pharmaceutical companies and medium players are looking for strategic partnerships with companies that have promising drugs either in the pipeline or in the market. In 2008-2009, a total of 35 M&A and licensing deals took place. Most of the M&A and licensing deals involved companies active in the diabetes market. The diabetes market needs drugs which are easier to administer and the obesity market requires drugs which do not have serious side effects.
This unmet need and the growth potential are driving the deals activity in the industry. The major acquisition activity that took place in 2008-2009 was GlaxoSmithKline's (GSK) acquisition of Sirtris Pharmaceuticals. The acquisition considerably added to the pipeline potential of GSK in the diabetes market. Licensing activities involving approved products such as Januvia and Galvus (vildagliptin) and Phase III products such as Oral-lyn will have an impact on the market.
Failure because of toxicity? No way!
There are a couple of reports regarding intolerable toxicity shown in clinical trials of Carfilzomib (see here and here):
Side effects for the treatment, known chemically as carfilzomib, also included cardiac arrest and shortness of breath, the FDA staff said. More than 70 percent of patients had lung complications with the drug, according to the FDA report.
Well, you may say that the drug is a failure... FDA basically should have the same opinion:
The agency “is very concerned with the severe toxicities, including deaths that are associated with the use of this agent,” the FDA staff said in the report.
However, do you know what? The clever experts who know this industry and understand how the things work, yes, they expect that the drug will be definitively approved! No doubt about it if the potential profit is so huge:
“This is a drug that will get approved,” Michael King, an analyst with Rodman & Renshaw in New York, wrote in an e-mail today. “It’s just a matter of when.”
If approved, yearly sales for the drug may be $523 million in 2016, according to the average of five analysts’ estimates compiled by Bloomberg.
Monday, June 18, 2012
Sunday, June 17, 2012
ABC of chain reaction
The physics and driving force are very simple - somebody has to create the system with a trigger and then somebody is just activate the trigger...
2nd order cybernetics is the art of working with trigers (this is my definition; more about cybernetics will come on the blog very soon)
Copaxone – very strange medicine
Copaxone (or Glatiramer) is absolutely worth of to be looked at. Everything is strange with this drug. For example, the structure is not strictly defined – it is a mixture of different polymers:
Poly[L-Glu13-15, L-Ala39-46, L-Tyr8,6-10, L-Lys30-37] x n CH3COOH
But the most interesting with this blockbuster is that the mechanism of its action is not specified in terms of modern R&D paradigm (the paradigm briefly described here, here and here):
The mechanism(s) by which glatiramer acetate exerts its effects in patients with Multiple Sclerosis (MS) is (are) not fully elucidated. However, it is thought to act by modifying immune processes that are currently believed to be responsible for the pathogenesis of MS. This hypothesis is supported by findings of studies that have been carried out to explore the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a condition induced in several animal species through immunization against central nervous system derived material containing myelin and often used as an experimental animal model of MS. Studies in animals and in vitro systems suggest that upon its administration, glatiramer acetate-specific suppressor T-cells are induced and activated in the periphery.
Well, I think we will continue follow the success of this medicine in the future
Epidemic of cancer and Big Pharma
The ranks of American cancer survivors are growing, and will increase from 13.7 million in January 2012 to nearly 18 million in January 2022, according to a report from the American Cancer Society and the National Cancer Institute.
Though an aging and growing population helps explain why more people are surviving cancer, the study says that improvements in treatment and more people getting screened also play a part.
The study reports that in 2012, male survivors were most likely to have had prostate cancer, colon and rectal cancer, and melanoma; most common among female survivors were breast, uterine, and colon and rectal cancers. The American Cancer Society predicts that nearly all of those will be the most commons cancers of survivors in 2022, too.
"The reasons that some cancers are more common in survivors than they are in newly diagnosed patients is that the common cancers among survivors are typically ones that are fairly common in the population of new diagnosis," Ward said, "but they are also cancers that have a fairly high survival rate."
Well, there is no better situation for Big Pharma – the cost of treatment is skyrocketing! Do you need example? The latest one: the drug named Zelboraf, or vemurafenib, is for malignant melanoma that has spread and carries a specific genetic mutation and costs around £1,750 per patient per week.
Saturday, June 16, 2012
Friday, June 15, 2012
World Preview 2018: Part 1. R&D productivity
Something
very exciting has happened: a
forecast of the pharmabusiness in 2018 has been issued. This document is
very detailed and it takes a lot of time to digest it; however a brief look
revealed the tendencies. I found this review very rational and absolutely worth
to be studied. The conclusions of the author regarding R&D productivity and
risen questions are very sober and in
the same line with my previous suggestions:
The Industry has spent $1.1 trillion over
the last 10 years in R&D (page 15). With hindsight this appears to be an
inefficient use of this surplus cash. It is often said there is an R&D
productivity issue, but is it just poor portfolio strategy and investment
choices? Is too much money being spent chasing too few quality R&D
projects?
We may question whether certain companies
should even continue with new product R&D activities given their track
record. AstraZeneca, for example, with a string of high profile R&D
disappointments in recent years, is so poorly rated by the stock market that
the current market capitalization of $50bn is 30% lower than the company’s
aggregate value of its entire portfolio of products at $72bn (as valued by
EvaluatePharma’s NPV Analyzer).
Additionally billions are spent by the
Industry in the potentially aggressive transfer of risky, late-stage in-process
R&D assets in seemingly high-priced and speculative in-licensing deals and
company acquisitions. An example is Gilead’s $11bn acquisition of Pharmasset in
early 2012 for access to the Hepatitis C treatment GS-7977. This product would
ultimately have been pursued regardless of whether Gilead owned it. The
decision to pursue these courses of action stems from a combination of:
1) over confidence after bringing a
blockbuster product to market that the same successcan be repeated;
2) the need to grow share price; and,
3) the availability of surplus cash flows
from ageing blockbusters.
Real numbers
and sober conclusions. I will definitively come back to this review – for more
details and trends.
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