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DRUG DEVELOPMENT DECONSTRUCTOR MANIFESTO: : “Tell me how you read and I'll tell you who you are.” ― Martin Heidegger
Tuesday, July 31, 2012
Another cure from cancer. Again! (Post No 11)
Yes, but today we have 3 magic cures! Two new usual “targeted” tyrosine kinase inhibitors: Ponatinib (from wiki:
The primary target for ponatinib is BCR-ABL, an abnormal tyrosine kinase that is the hallmark of CML and Ph+ ALL. CML is characterized by an excessive and unregulated production of white blood cells by the bone marrow due to a genetic abnormality that produces the BCR-ABL protein. After a chronic phase of production of too many white blood cells, CML typically evolves to more aggressive phases such as accelerated or blast crisis. Ph+ ALL is a subtype of acute lymphoblastic leukemia that carries the Ph+ chromosome that produces BCR-ABL. It has a more aggressive course than CML and is often treated with a combination of chemotherapy and tyrosine kinase inhibitors. Because both of these diseases express the BCR-ABL protein, this would render them potentially susceptible to treatment with ponatinib. BCR-ABL is detected in 95% of patients with CML. Patients with CML currently receive front line therapies nilotinib and/or dasatinib though 22-33% of patients discontinue therapy by two years due to adverse events, treatment failure and other causes.)
and Cabozantinib:
Ariad Pharmaceuticals Inc. (NASDAQ:ARIA) began submission of a rolling NDA to FDA for ponatinib to treat resistant or intolerant chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). The company, which requested Priority Review for the application, is seeking accelerated approval for ponatinib based largely on data from the pivotal Phase II PACE trial. In June, Ariad reported data showing that 54% of chronic phase CML patients who were resistant or intolerant to tyrosine kinase inhibitor therapy, including 70% of patients with the T315I variant of BCR-ABL tyrosine kinase, achieved a major cytogenetic response. Ariad's proposed indication includes, but is not limited to, patients with the T315I mutation.
…
Exelixis, Inc. (EXEL) today announced that the U.S. Food and Drug Administration (FDA) has accepted for filing the New Drug Application (NDA) for cabozantinib as a treatment for patients with progressive, unresectable, locally advanced, or metastatic medullary thyroid cancer (MTC). The FDA also granted priority review designation to the NDA for cabozantinib.
Cabozantinib is a potent inhibitor of MET, VEGFR2 and RET. RET is a receptor tyrosine kinase that is frequently activated by point mutation in medullary thyroid carcinomas. The therapeutic role of cabozantinib is currently being investigated across several tumor types. MET is upregulated in many tumor types, thus facilitating tumor cell escape by promoting the formation of more aggressive phenotypes, resulting in metastasis. MET-driven metastasis may be further stimulated by hypoxic conditions in the tumor environment, which are often exacerbated by selective VEGF-pathway inhibitors. In preclinical studies, cabozantinib has shown powerful tumoricidal, antimetastatic and antiangiogenic effects, including:
•Extensive apoptosis of malignant cells
•Decreased tumor invasiveness and metastasis
•Decreased tumor and endothelial cell proliferation
•Blockade of metastatic bone lesion progression
•Disruption of tumor vasculature
But the third approach is not usual targeted bogus – it looks like really rocket science which is really worth of citation!
Senesco’s therapeutic candidate, SNS01-T comprises three components: a DNA plasmid, a small inhibitory RNA (siRNA) and polyethylenimine (PEI). The DNA plasmid expresses eIF5AK50R (human eIF5A containing a lysine to arginine substitution at amino acid position 50) that up-regulates the apoptotic pathways within cancer cells. By RNA inhibition (RNAi), the siRNA down-regulates the production of hypusine eIF5A and by this mechanism suppresses anti-apoptotic proteins, NF-kB, ICAM and pro-inflammatory cytokines, which are proliferation factors for multiple myeloma. PEI is a cationic polymer that promotes self-assembly of nanoparticles with demonstrated enhanced delivery to tissues and protection from degradation in the blood stream.
SNS01-T is the subject of an open IND and an on-going study in multiple myeloma.
Preclinical studies have shown that SNS01-T is able to promote the elimination of cancer cells through multiple validated mechanisms including:
i. Down-regulating NFkB and anti-apoptotic proteins
ii. Up-regulating p53 and pro-apoptotic proteins
iii. Blocking the IL-6 paracrine growth signal among cells in the tumor environment
The DNA plasmid for eIF5AK50R is under the control of the B29 promoter and enhancer, which has been shown to restrict expression to B-cells (Hermanson et al, 1989; Hermanson et al, 1988; Malone et al, 2006). The mode of action of SNS01-T employs an eIF5A-specific siRNA to reduce the pool of hypusinated eIF5A in myeloma cells, while simultaneously producing eIF5AK50R that mimics the lysine protein, but cannot be hypusinated. This approach promotes apoptosis of multiple myeloma cells, while simultaneously depleting cellular levels of hypusinated eIF5A, which normally protects the cells from apoptosis. SNS01-T reduces tumor burden in murine myeloma models without damaging normal tissues.
I am impressed, aren't you? Not yet? Well, the approach can be promising for treatment of both mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL)!
Senesco Technologies, Inc. (“Senesco” or the “Company”) (NYSE MKT: SNT) reported today that it was informed on July 26th that the U.S. Food and Drug Administration (FDA) has granted orphan-drug designation for the company’s lead drug candidate SNS01-T for treatment of both mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL).
Let's hope that all these 3 drugs will help somehow to fight cancers!
Monday, July 30, 2012
Another magic cure. Alcohol as enhancer of medicine action
No joke!
From here:
According to new research, alcohol combined with certain medications not only opens up the risks of liver damage, stomach bleeding and other side effects, it also makes those drugs “three times more available to the body, effectively tripling the original dose.”
Well, in general, if you take into account the price of medicines, it is very positive news! Let's drink simultaneous with medication and safe money!
Sunday, July 29, 2012
Another cure from cancer. Again! (Post No 10)
This time we are talking about... adjuvants as part of the therapy to increase the efficacy by helping maximize the immune response.
Well, the article describes several adjuvants which according to the author can be potentially promissing BUT I think most important messages of the article:
- Adjuvants will not replace standard chemotherapy, radiotherapy, surgery etc – the adjuvants can only some how improve the standard treatment
Author clearly understand that novel “targeted” approaches are not magic bullets (which is definitively true):Hormone therapy (often used for prostate cancer), targeted chemotherapy via antibody-drug conjugates, and a host of other advancements offer more options than ever for patients fighting many manifestations of the dreadful disease. However, with all these advancements something is beginning to be painfully clear for at least the interim; there may be no current magic bullet for fighting many cancers, but instead physicians' best weapons may involve a combination approach to combating the disease in its many forms.
Saturday, July 28, 2012
Masterpiece of the day. Pizda?
According to wiki this is the structure of PIZDA (!!!).
Well, I thought it should look in a some different way!
Well, I thought it should look in a some different way!
Another cure from cancer. Again! (Post No 9)
And again it is a “targeted” medicine! In previous attempt as an active part was used doxorubicin. In the present approach – lead-212.
Areva Med LLC (Bethesda, Md.) partnered with Roche (SIX:ROG; OTCQX:RHHBY) to develop an alpha radioimmunotherapy platform to treat cancer. Roche's Pharma Research & Early Development organization (pRED) will combine the pharma's antibodies with Areva's radionuclide, Lead-212. Roche will have exclusive commercialization rights to the radioimmunotherapy after clinical development. Details were not disclosed. Lead-212 is an isotope that is part of the thorium-228 decay chain. Areva Med is a subsidiary of Areva (Euronext:AREVA).
Well, the same targeted approach. Will this particular attempt break the negative expectations regarding “targeted” drugs?
Friday, July 27, 2012
Thursday, July 26, 2012
Masterpiece of the day. Knowledge is power
Богданов-Бельский Николай Петрович. <<У дверей школы>>, 1897.
Erooms law in action
Fewer new prescription drugs will get approved in the U.S. this year than the 30 approved in 2011, a ratings agency forecasts, adding to the many stresses on the pharmaceutical industry.
The Food and Drug Administration approved only 14 innovative drugs in the first half of this year, down from 18 in the first half of 2011, according to a report released Wednesday by Fitch Ratings.
“Branded pharmaceutical developers’ research success of 2011 will be difficult to repeat,” the report states.
The report comes as big brand-name drugmakers are being squeezed from all sides — and their second-quarter results are showing the effects.
Government and other health plans, particularly in debt-laden Europe, continue to push drugmakers to lower prices. The weak global economy has many consumers delaying treatments or looking for cheaper alternatives. And an unprecedented tidal wave of generic competition for many top-selling drugs is slashing the billions of dollars they had been bringing drugmakers.
Since last October, three of what had been the world’s 10 best-selling drugs have gotten generic competition. Those are the long-time best-seller Lipitor, Pfizer Inc.’s high cholesterol pill, plus psychiatric drug Zyprexa and blood thinner Plavix. Next week, another top 10 drug, Merck & Co.’s asthma and allergy pill Singulair, gets generic rivals.
Pharmaceutical companies are still very profitable, but that’s mainly because they’ve been on a tear for several years, slashing jobs and closing factories and research centers to cut their costs ahead of what the industry terms the “patent cliff.” Virtually every major drugmaker has recently had drugs with annual sales of $1 billion or more get generic competition, or it’s right around the corner
Well, the decrease in the number of drugs was expected - Erooms law works excellent!
Another cure from cancer. Again! (Post No 8)
CytRx Corporation announced the initiation of a Phase 1b clinical trial to determine the maximum tolerated dose and to evaluate preliminary efficacy of aldoxorubicin (formerly INNO-206) administered in combination with the commonly used chemotherapeutic agent doxorubicin in patients with advanced solid tumors who have failed other therapies. Aldoxorubicin is a tumor-targeting conjugate of doxorubicin. The single-center Phase 1b clinical trial will be conducted under the direction of Dr. Chawla and will enroll up to 24 patients. Doxorubicin will be administered at 50% of its maximum tolerated dose in combination with escalating doses of aldoxorubicin to determine the maximum tolerated dose of the combination of these two drugs in this patient population.
And what do we have here is the “novel” targeted magic bullet which supposed to be more efficient and less toxic but not necessarily :(
Big Pharma – big money injection is needed!
From here:
The European Commission is calling for views on its plans to establish a public/private partnership (PPP) in life sciences research and innovation.
Based on the success of the Innovative Medicines Initiative (IMI), the Commission is proposing to set up a life sciences PPP within Horizon 2020, its flagship, 80 billion-euro initiative which is set to run from 2014-2020 with the aim of establishing Europe's global competitiveness.
…
Discussing the reasons for its proposal, the Commission notes that the challenges facing the healthcare sector in Europe are very large, and include not only an ageing population and a concomitant rise in chronic and degenerative diseases, but also new infectious diseases and the spread of antibiotic resistance.
The pharmaceutical industry and the entire life science innovation ecosystem are also under increasing economic pressure, it adds. The time from a basic discovery to a new drug or vaccine becoming available for patients averages 10-15 years, and many important basic academic findings never enter the innovation cycle because of gaps in knowledge, lack of incentives or appropriate training or investments, particularly in the early stages of translation - the so-called "valley of death."
Despite the strong science base in Europe and promising research results, a number of barriers continue to discourage the private sector from translating research results into novel health services and products, not least being need for multidisciplinary solutions for medical problems, it notes, adding: "as a result, the innovative power of academia, small or medium-sized enterprises (SMEs) and large companies is underused, and innovation processes falter and happen too slowly."
Yes, absolutely! Big Pharma has problems and desperately needs these €80b! Well, these money will come out from our (taxpayer's) pockets but this is another story
To short Big Pharma or go long?
What did these persons have in common? They definitively had a plan! Do you have a plan?
Wednesday, July 25, 2012
28 drugs facing FDA Approval 2012-2013
From here
The calendar on the following pages captures the most important U.S. regulatory events -- FDA drug approvals and advisory panels -- expected between July and February 2013. As every savvy biotech investor and trader knows, the volatility in biotech and drug stocks ramps significantly as U.S. regulators weigh whether to approve or reject new drugs.
Well, sure, this information can be interesting for plaining on the market! I think it can be very profitable the strategy of going short for all 28 companies! Of course, some of the drugs will be approved but the magority will fail providing sweet return on the invested money :)
Tuesday, July 24, 2012
And the good news is...
From here.
Pfizer Inc. said Friday that a European Union advisory panel recommended that its lung cancer drug Xalkori get conditional marketing approval.
The panel recommended that Xalkori be approved conditionally for use in patients who have already received at least one treatment for lung cancer. The non-binding opinion will be considered by EU regulators. Pfizer said that if Xalkori gets conditional approval, it will be required to submit data from a recently completed clinical trial. Regulators could give the drug full approval after reviewing those results.
Drugs that address unmet medical needs sometimes get conditional approvals so patients can use the products before they get full marketing approval. Xalkori targets cancer linked to a genetic mutation found in less than 7 percent of non-small cell lung cancer patients.
Well, it is really lucky news for those 7% who has these special mutation. The doctors are probably inform patients in a following way: "I have two news for you: one bad and one good. The bad news is that you have non-small lung cancer, and the good one is that the cancer has a special mutation..."
Monday, July 23, 2012
Sunday, July 22, 2012
Saturday, July 21, 2012
Friday, July 20, 2012
Targeted but MORE toxic?
Just again about targeted medicine. I have found a real masterpiece about this issue:
The study showed the newer cancer drugs caused significantly more side effects, and more treatment-related deaths, than their older counterparts. "You've got to consider both efficacy and toxicity in the picture," said Susan Ellenberg, who has studied drug side effects at the University of Pennsylvania's Perelman School of Medicine.
Well, I am completely lost: we were told that targeted medicines a priori (due to they ARE targeted) are more efficient and LESS toxic compared to non-targeted ones! Somebody has to help me in connecting the dots!
Targeted drug Brivanib misses the target
If you follow my blog you have to know that I strongly believe that the "targeted" approach in drug development is pseudo-scientific and very often we can see the failures of targeted drugs. A fresh example:
Bristol-Myers Squibb Co. (BMY) said a Phase 3 trial of its drug, brivanib, as a first-line treatment in patients with liver cancer didn't meet its primary survival objective
Thursday, July 19, 2012
"Pay-for-delay" trick is over?
Pay-for-delay is very powerful weapon in the arsenal of Big Pharma tricks. It looks like some changes will come:
The Third U.S. Circuit Court of Appeals, based in Philadelphia, delivered a jolt to the pharmaceutical industry on Monday, coming down hard on settlements in which branded drug companies pay generic drug makers to stay off their backs.
They are called “reverse payments” or “pay-to-delay” settlements.
Generic drug makers can challenge the validity of brand manufacturers’ patents in federal court, in a bid to bring their generic drugs to market faster. But brand-name drug manufacturers can pay their way out of the litigation. Essentially, they give generic companies money — lots of it — to temporarily stay out of the market.
Until Monday, the prevailing law on these settlements presumed they were perfectly legitimate, as long as branded drug makers weren’t paying to keep (much cheaper) generic drugs off the market after patents on their brand-name drugs expired.
The U.S. government hates these settlements — because they allow for the possibility that weak patents that otherwise would have been wiped out by a legal challenge can live on if the patent holder is willing to pay to protect them. Thus, it takes longer for a given generic drug to get to the market and consumers pay more in the meantime. (A 2010 analysis by the FTC found that reverse payment settlements cost consumers $3.5 billion annually.)
Wednesday, July 18, 2012
GSK scandal. ABC of Big Pharma way of business
From here
And we have to expect that these criminal approaches described here are common for ALL Big Pharma companies, not just for GSK...
MS battles era is coming
I have read this news article – it looks like MS will be field of big epic battles in the nearest future. The market is very impressive!
MS is an autoimmune disease that affects about 2.1 million people worldwide …
Avonex, made by Biogen, Bayer’s Betaseron and Merck KGaA (MRK)’s Rebif generated $6.6 billion in 2011 revenue, according to data compiled by Bloomberg. Called disease-modifying drugs, they have been shown to slow the frequency of relapses and reduce the development of brain lesions. Their ability to slow disability progression has been less clear, wrote the researchers
Tuesday, July 17, 2012
David Brennan, the former chief of AZ: one live in paradise
The message here is that there is no any responsibility for to be a chief of AZ. If he does the business well – he benefits, if he destructs the company – he benefits too! This is a perfect situation. How the usual person should proceed? Just go fishing or diving or travelling or... - whatever, - he is already in a paradise!
Monday, July 16, 2012
Sunday, July 15, 2012
Trendfollowing?
Trend-triggers should sound better and more correct as a name for the followers of this trading approach..
Attention: No 20 is wrong! Otherwise – very motivated and pedagogic summary of the rules how to be prepared for the next move of market/live...
Saturday, July 14, 2012
Higg's boson and cryptomatics
The following video describes the view of the mainstream.
http://www.russia.ru/video/diskurs_13327/
Well, what we've got here is a perfect example of cryptomatics - a simulacra of a science, a science without ontology... Mainstream is senceless...
http://www.russia.ru/video/diskurs_13327/
Well, what we've got here is a perfect example of cryptomatics - a simulacra of a science, a science without ontology... Mainstream is senceless...
Alzheimer's Drug Research Problems
Very interesting analysis.
But there’s plenty of reason to believe these studies tests will be inconclusive. The biggest worry is that even if the drugs work, the studies may show that to be effective, the medicines must be used much like anti-cholesterol pills, well before the disease begins to show debilitating symptoms. If that’s true it will mean years of uncertainty about an effective treatment or cure. Alternately, the drugs may turn out to be complete busts, or only improve memory and thinking in a statistically negligible manner that will spark conflicting interpretations. And since there is nothing in drugmakers’ pipeline to replace the drugs being tested, negative results will force Alzheimer’s research back to square one for a disease that is already costing untold suffering and adding hundreds of millions of dollars a year in health costs that will explode as the population ages.
And the main paradigm looks in the following way:
The experimental medicines all focus on attacking beta amyloid, a protein autopsies show masses in the brains of Alzheimer’s victims. According to the amyloid theory, these packets of plaque destroy brain cells over time, though exactly how they do this is still unknown. One school of scientists believes the plaques, which collect in small amounts in nearly all people as they reach old age, arise earlier and in much larger amounts in people with a predisposing genetic makeup. Another group argues that the clumping is merely the residue of some other unknown chain of events, so drugs designed to prevent or destroy amyloid will provide little if any benefit.
Well, again the key-lock strategy – if you remove amyloid, you will cure the patient. Isn't this approach too mechanistic?
Medical research and literature. 40% corrupted.
Roughly 40% of the sizeable medical research and literature on recently approved drugs is “ghost managed” by the pharmaceutical industry and its agents. Research is performed and articles are written by companies and their agents, though apparently independent academics serve as authors on the publications. Similarly, the industry hires academic scientists, termed key opinion leaders, to serve as its speakers and to deliver its continuing medical education courses. In the ghost management of knowledge, and its dissemination through key opinion leaders, we see the pharmaceutical industry attempting to hide or disguise the interests behind its research and education.
Well, the phenomenon is known, sure, but the scale of 40% (!) is really surprising. How can we really trust in the “scientific” literature if there is 40% probability of fake?
Friday, July 13, 2012
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