Why Malaria Is Prevalent, By Senators, NIMR .
Friday, 19 April 2013 19:15 By Joseph Okoghenun News - National
.SENATE Committee on Health blamed what its called “ economics of malaria control”- a euphemism for international politics for economic reason- as one reason why malaria is still persistent in Nigeria, in spite of billions of naira being spent by the Federal Government to arrest the situation.
The committee, which made the observation in Lagos yesterday during its oversight visit to the Nigerian Institute of Medical Research (NIMR), said it was not convinced that the long-lasting insecticide-treated nets (LLINs) programme being bankrolled by the Federal Government was the solution to the incessant case of malaria infection in the country.
Chairman of the committee, Dr. Ifeanyi Okowa, wondered why Nigeria would still continue to cling to the strategy, which he said was not working, when country like Senegal that has manufacturing plants for LLINs was using other effective means to tackle malaria.
Okowa said he was going to speak up on the matter when he return to Abuja as his past attempts to speak on it had met deaf ears.
While the Minister of State for Health, Dr.Muhammad Ali Pate, said in January that the ministry proposed N1.8 billion for the procurement of LLINs for additional three states, a World Health Organisation (WHO)’s report shows that Nigeria would need one billion dollars (N158 billion) to stave off backsliding and resurgences of malaria in 2013 and 2014.
Malaria still remains one of the most dangerous diseases in Nigeria, contributing to high level of Under-5 and maternal deaths. Distribution of LLINs has been government’s retrogressive intervention mechanism to reduce burden.
NIMR Director-General,Prof. Innocent Ujah, said research had shown that some Nigerians, especially from the Eastern part of the country, do not use LLINs for cultural reasons, thereby rendering the strategy ineffective.
Ujah, who was specifically asked by the committee to access the strategy, said LLINs are not the best for the country as other countries that have eradicated malaria had used indoor residual spray.
Ujah, who regretted that research was not being given prominent place in national development, called on government to establish National Health Research Fund to fund research appropriately.
NIMR Head of Public Health and Malaria Programme, Dr. Samson Awolola, said “we have shown that best method of tackling malaria is indoor residual spray”, adding that LLINs were supposed to be palliative mechanism to tackle malaria menace.
------------------------------------------------------------------------------------
Short communication: Authentication of artemether,
artesunate and dihydroartemisinin antimalarial tablets
using a simple colorimetric method
Michael D. Green, Dwight L. Mount and Robert A. Wirtz
Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA
Summary The recent and widespread appearance of counterfeit antimalarial tablets in South±east Asia prompted
the search for simple ®eld assays to identify genuine drugs. In a recently described colorimetric assay for
artesunate, Fast red TR salt reacted with an alkali-decomposition product of artesunate to produce a
distinct yellow colour. However, that assay is speci®c for artesunate and it cannot be used to test for
artemether. Because of potential concerns over artemether tablet counterfeiting, the colorimetric assay
was modi®ed to detect artemether, dihydroartemisinin and artesunate tablets. Other common
antimalarials (artemisinin, chloroquine diphosphate, me¯oquine HCl, sulphadoxine and pyrimethamine),
as well as aspirin and acetaminophen, were negative in the assay, indicating its speci®city for
artemether, dihydroartemisinin and artesunate. The colorimetric method can be used to obtain a rapid
visual assessment of tablet authenticity. The method can also be used to quantify the drug content of
tablets, when used in conjunction with a spectrophotometer.
keywords artemether, dihydroartemisinin, artesunate, artesunic acid, colorimetric, malaria, Fast red
TR, diazonium salt, counterfeit
correspondence Michael D. Green, Centers for Disease Control and Prevention, 1600 Clifton Road
N.E. Mailstop F-12, Atlanta, GA 30333, USA. Fax: +1-770-488-4108; E-mail: mdg4@cdc.gov
Introduction
The artemisinins are increasingly being used because of
their effectiveness against multi-drug resistant malaria.
This family of drugs is derived from the natural product
artemisinin and includes artemether (AM), artesunate
(ARTS) and dihydroartemisinin. Reports of the distribution
of counterfeit artesunate tablets in South±east Asia are
becoming more frequent. In 1999, an investigation into the
sale of counterfeit artesunate revealed that 71% of the drug
vendors and pharmacies sampled in Cambodia sold the
counterfeit drug (Rozendaal 2001). In response to this
serious health threat, Green et al. (2000) developed and
validated a colorimetric ®eld test [ARTS-Fast red TR
(FRTR)] to distinguish genuine artesunate from counterfeit
tablets. In conjunction with organoleptic evaluation, the
ARTS-FRTR test was used to survey the extent of the
distribution of counterfeit artesunate tablets collected in
South±east Asia. Initial testing has shown that 38% of
artesunate tablets tested in South±east Asia contained no
active ingredient (Newton et al. 2001). Distribution of
counterfeit artemisinin derivatives, such as artemether and
dihydroartemisinin has not been documented to date, but
these drugs are similar in cost and appearance to artesunate
and it is likely that they will become targets of counterfeiting.
As artemether is not detected in the ARTS-FRTR
test (Green et al. 2000), we modi®ed this assay to identify
the presence of artemether as well as dihydroartemisinin
and artesunate.
Materials and methods
Fast red TR salt (reagent grade; dye content approximately
20%) was purchased from Sigma-Aldrich Fine Chemicals
(Milwaukee, WI, USA). Artemether and dihydroartemisinin
were a gift from Dr P. Olliaro, World Health
Organization. Artesunate was produced by Mepha (Aesch-
Basel, Switzerland). ArenaxÒ tablets (100 mg b-artemether
Tropical Medicine and International Health
volume 6 no 12 pp 980±982 december 2001
980 ã 2001 Blackwell Science Ltd
per tablet) were manufactured by Arenco Pharmaceutica,
Belgium. MalaxinÒ (60 mg dihydroartemisinin) was manufactured
by Dongsan Pharmaceutical Co. Ltd., South
Korea and ArsumaxÒ (50 mg artesunate) was produced by
Guilin Pharmaceutical Works, China (the use of trade
names is for identi®cation only and does not imply
endorsement by the Public Health Service or the US
Department of Health and Human Services). The buffering
reagent consisted of 0.1 M borate in 5% ammonia
solution. FRTR solution (5 or 10 mg/ml water) was
prepared immediately before sample addition. Absorbance
measurements were recorded with a Spectronic-20 (Bausch
and Lomb Inc., Rochester, NY, USA) spectrophotometer
set at 420 nm. All reagents were prepared with de-ionized
water and were analytical grade, unless noted otherwise.
Assay procedure (AM-FRTR test)
The assay procedure is as follows: scrape about 5% of the
tablet mass into a glass tube, add 0.4 ml of methanol and
mix for about 10 s, add 0.4 ml of 5 N HCl and incubate
the sample at room temperature (22±27 °C) for at least
1 h, add 2.2 ml of buffering solution. Add 0.1 ml of FRTR
solution and thoroughly mix. A yellow colour develops
within 5 min if artemether, dihydroartemisinin or artesunate
is present in the sample.
The speci®city of the AM-FRTR test was assessed by
testing other common antimalarial tablets (Table 1). Each
tablet was weighed and 5% of the tablet mass was added
to a glass tube. Methanol (0.5 ml) was added and the
samples vortexed for 10 s. Insoluble tablet excipients were
centrifuged (500 g; 10 min) and 0.4 ml of the supernatant
was transferred to a clean glass tube. To perform the
quantitative analysis, the tablet and scrapings were
weighed and the insoluble excipient centrifuged. Subsequently,
steps 3±5 were performed as described above.
For quantitative assessment, standard curves were prepared
from artemether, dihydroartemisinin and artesunate
at concentrations of 0.5, 1 and 2 times the concentration
determined for 5% of Arenax (100 mg artemether),
Malaxin (60 mg dihydroartemisinin), or Arsumax (50 mg
artesunate) in 0.5 ml of methanol. Absorbance (420 nm)
values were recorded for the standard curve and tablet
samples. Linear regression analysis of absorbance vs.
concentration data from the standard curve samples was
used to calculate the concentration of the active ingredient
for each tablet. Two ml of ethyl acetate was added to the
solution and the sample thoroughly shaken. After phase
separation, quantitative analysis of the yellow reaction
product extracted into the organic phase was assessed as
described above.
Formation of artemether acid decomposition product
The diazo-coupling reaction of FRTR with artemether
depends on the formation of an acid decomposition
product. This product, described by Thomas et al. (1992),
is an a, b-unsaturated decalone that absorbs ultraviolet
radiation at 254 nm. The optimum incubation period for
its formation was assessed by adding 2 ml of 5 N HCl to
0.1 ml of artemether (1 mg/ml methanol) and monitoring
the absorbance at 254 nm for 4 h.
Table 1 Speci®city of AM-Fast red TR (AM-FRTR) test with other commonly used antimalarials. Per cent accuracy is de®ned as the
difference between the expected value and calculated value divided by the expected value times one hundred. Calculated amount of active
ingredient (mg/tablet) and per cent accuracy are given before and after (*) ethyl acetate extraction
Calculated active ingredient Calculated active ingredient*
Drug Active ingredient per tablet Colour mg/tablet % accuracy mg/tablet % accuracy
Arenax b-artemether, 100 mg Yellow 108 8 110 10
Acetominophen Acetominophen, 325 mg Faint orange ± ± ± ±
Asprin Acetylsalicylic acid, 325 mg Colourless ± ± ± ±
Artemisinin Artemisinin, 50 mg Colourless ± ± ± ±
Arsumax Artesunate, 50 mg Yellow 18 65 45 11
Aralen Chloroquine diphosphate, 250 mg Colourless ± ± ± ±
Malaxin Dihydroartemisinin, 60 mg Yellow 69 15 33 46
Lariam Me¯oquine HCl, 250 mg Colourless ± ± ± ±
Falcidin Sulphadoxine, 500 mg/
pyrimethamine, 25 mg
Colourless ± ± ± ±
Co-trimoxazole Sulphamethoxazole, 400 mg/
trimethoprim, 80 mg
Colourless ± ± ± ±
Tropical Medicine and International Health volume 6 no 12 pp 980±982 december 2001
M. D. Green et al. Authentication of antimalarials
ã 2001 Blackwell Science Ltd 981
Results
A distinct yellow colour is apparent for the AM-FRTR test
in the presence of artemether, dihydroartemisinin or
artesunate (Table 1). A faint orange colour appeared in the
presence of acetaminophen, while the other antimalarials
appeared colourless. After several hours, a weak yellow
colour appeared in the drugs containing the sulphonamides,
i.e. Falcidin (500 mg sulphadoxine) and co-trimoxazole
(400 mg sulphamethoxazole). Quantitative
analysis using absorbance measurements showed the
artemether content of Arenax and the dihydroartemisinin
content of Malaxin to be within 15% of expected values,
while the artesunate content of Arsumax showed a much
greater deviation of 65% (Table 1). All samples appeared a
bit cloudy, especially Arsumax, which may have contributed
to a greater deviation. Therefore, extraction with
ethyl acetate was employed in an effort to improve
accuracy. After addition of 2 ml of ethyl acetate followed
by vigorous shaking, the entire yellow reaction product
migrated into the organic phase. From absorbance measurements,
the active ingredients for each tablet were
calculated (Table 1). Ethyl acetate extraction showed
improved accuracy (% deviation from expected value) of
artesunate content in the Arsumax tablet from 65% to
11%, while the Malaxin tablet showed a greater deviation
(46%) of dihydroartemisinin from the expected value. This
may by attributable to preferential solubility of the reaction
products in ethyl acetate relative to the aqueous buffer.
Although optimum conversion of artemether into its
decomposition product occurs at about 4 h, colorimetric
detection of a 5% tablet containing 100 mg artemether is
easily achieved if incubated for at least 1 h. This observation
was also evident with dihydroartemisinin and
artesunate.
Discussion and conclusions
The artemisinins do not have the particular chemical
groups that easily react with certain reagents to yield
coloured products, however, they can be transformed by
acid or base treatment to more reactive compounds, i.e.
enolate/carboxylates or a, b-unsaturated decalones (Zhao
& Zeng 1986; Thomas et al. 1992). These compounds
react readily with diazonium salts (Zollinger 1991). Green
et al. (2000) demonstrated that the alkali-decomposition
product of artesunate react with the diazonium salt, FRTR,
to produce a yellow product correlating well with artesunate
concentration. As the ARTS-FRTR test did not
respond to artemether, a strategy of converting artemether
to the reactive a, b-unsaturated decalone was implemented
as a means of adapting the ARTS-FRTR test to detect and
quantify genuine artemether as well as dihydroartemisinin
and artesunate. A qualitative or semi-quantitative assessment
of the drug can be determined visually, i.e. without
the need for a spectrophotometer, by comparing the colour
intensity of the sample to solutions of known drug content.
The speci®city and simplicity of this colorimetric method
(AM-FRTR test) will certainly be useful in detecting
counterfeit artemether, artesunate and dihydroartemisinin
in the ®eld.
References
Green MD, Mount DL, Wirtz RA & White NJ (2000) A
colourimetric ®eld method to assess the authenticity of drugs
sold as the antimalarial artesunate. Journal of Pharmaceutical
and Biomedical Analysis 24, 65±70.
Newton P, Proux S, Green M et al. (2001) Fake artesunate in
southeast Asia. Lancet 357, 1948±1950.
Rozendaal J (2001) Fake antimalaria drugs in Cambodia. Lancet
357, 890.
Thomas CG, Ward SA & Edwards G (1992) Selective determination,
in plasma of artemether and its metabolite, dihydroartemisinin,
by high-performance liquid chromatography
with ultraviolet detection. Journal of Chromatography 583,
131±136.
Zhao S & Zeng M (1986) Application of precolumn reaction to
high-performance liquid chromatography of qinghaosu in animal
plasma. Analytical Chemistry 58, 289±292.
Zollinger M (1991) Colour Chemistry: Synthesis, Properties and
Applications of Organic Dyes and Pigments. VCH, New York,
p. 119.
Tropical Medicine and International Health volume 6 no 12 pp 980±982 december 2001
M. D. Green et al. Authentication of antimalarials
982 ã 2001 Blackwell Science Ltd
Copyright of Tropical Medicine & International Health is the property of Wiley-Blackwell and its content may
not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written
permission. However, users may print, download, or email articles for individual use.
-----------------------------------------------------------------------------------
Survival gene discovery exposes HIV, hepatitis secrets .
Thursday, 29 November 2012 00:00 Editor Features - Science
.A NEWLY discovered gene that is essential for embryo survival could also hold the key to treating and potentially controlling chronic infections such as Human Immunodeficiency Virus (HIV), hepatitis and tuberculosis. The gene, called Arih2, is fundamental to the function of the immune system, making critical decisions about whether to switch on the immune response to an infection.
Its discovery has implications for the treatment of chronic overwhelming infections, such as HIV, that ‘exhaust’ and switch off the immune system, as well as, for chronic inflammatory (also known as autoimmune) conditions such as rheumatoid arthritis and sepsis.
Dr. Marc Pellegrini, Dr. Greg Ebert and colleagues from the institute’s Infection and Immunity division, with collaborators from the University of Toronto, Canada, led the research. Their findings were published November 26 in the journal Nature Immunology.
Infectious disease specialist and researcher, Pellegrini said that Arih2 is found in dendritic cells, the sentinels of the immune system that play an essential role in raising the alarm about the presence of foreign invaders in the body.
“Arih2 is responsible for the most fundamental and important decision that the immune system has to make, whether the immune response should be initiated and progressed or whether it should be switched off to avoid the development of chronic inflammation or autoimmunity,” Pellegrini said, “if the wrong decision is made, the organism will either succumb to the infection, or succumb to autoimmunity.”
Pellegrini said although our immune system works well against many infections, some organisms have developed mechanisms to evade or counteract the immune system, allowing them to persist in the body. “During evolution, some organisms have evolved ways of exhausting our immune system to the point where the immune system just switches off, and this is what happens in HIV, hepatitis B and tuberculosis,” he said.
“These organisms counter the immune response, exhausting T cells, which are stimulated over and over again by the infection and becoming exhausted or paralysed. With this current discovery, what we should be able to do is circumvent these mechanisms and reinvigorate the immune response temporarily to boost the immune system and help clear these infections.”
Ebert said the research team was now looking at the effect on the immune response of switching off Arih2 for short periods of time during chronic infections. “We are investigating how manipulating Arih2 and associated pathways promotes immunity in chronic overwhelming infections, where we know the immune response is inadequate,” Ebert said.
He said Arih2 had significant promise as a drug target. “Arih2 has a unique structure, which we believe make it an excellent target for a therapeutic drug, one that is unlikely to affect other proteins and cause unwanted side-effects,” Ebert said.
“Because Arih2 is critical for survival, we now need to look at the effect of switching off the gene for short periods of time, to see if there is a window of opportunity for promoting the immune response to clear the infection without unwanted or collateral damage or autoimmunity.”
Pellegrini said it would take many years to translate the discovery to a drug that could be used in humans. “We are very excited about this discovery,” Pellegrini said.
“Arih2 is the one of the most important genes involved in the most fundamental and vital decisions that the immune system has to make, whether or not to switch on the immune response to an infection. This discovery has significant implications for manipulating the immune response to infections and suppressing chronic inflammation or autoimmunity because we can target this gene to try to push immune responses in one or other direction, either promoting it or suppressing it,” Pellegrini said. “It is probably one of the few genes and pathways that is very targetable and could lead to a drug very quickly.”
------------------------------------------------------------------------
‘Nigeria still a spectator in N41bn global biotechnology industry’ – PSN President
ON FEBRUARY 9, 2012 • IN BUSINESS
The Pharmaceuticals industry in the country currently contributes less than 5 percent to GDP (gross domestic product). In this interview, with Chioma Obinna, the President of the Pharmaceutical Society of Nigeria, PSN, Pharm. Azubuike Okwor, says despite the injection of N200 billion Pharmaceutical Development Fund by the Federal Government, Nigeria is but only a spectator in the 41 billion naira global biotechnology industry. Excerpts:
What is the state of the pharmaceutical industry in Nigeria today?
The Pharmaceutical Industry is a very important sector in any nation’s economy, especially because of its capacity to ensure the health of the citizens and its contribution in wealth creation and reduction of poverty.
The development of the pharmaceutical industry in Nigeria has gone through a challenging evolution from the traditional infusion from a cocktail of leaves, roots and barks to small scale manufacture of tablets, syrup and recently sterile products. The industry has also done well given the environment that they have had to contend with in the last decade.
What is the industry’s contribution to the GDP, yearly?
The Nigerian manufacturing sector (including pharmaceuticals) is relatively small as reflected in its current contribution to the GDP which is below 5 percent. A recent survey by the Federal Ministry of Health highlighted major threats to the pharmaceutical sector including but not limited to, low capacity utilisation, poverty and related lack of purchasing power, high production cost, counterfeit and fake drugs, and failure of government to play the stewardship role.
The implication is our failure to take advantage of the opportunities created by the high demand for drugs used to treat the new pandemics of HIV&AIDS, Tuberculosis and Malaria across the developing world. In spite of the identified weaknesses, the industry has grown at an average annual rate of 10 percent over the last five years.
How about capacity utilisation in the industry?
The capacity utilisation for the pharmaceutical industry in Nigeria is about 40 per cent and there is capacity for production of certain types of drugs to meet national needs for essential drug and for export.
This explains why government has placed a ban on the importation of certain categories where we have enough capacity and expertise and also as a measure to protect local industries. The local industry even at these installed capacity can only meet 25 per cent of local needs, most of the manufacturers produce liquid preparation tablets, capsules, ointments, lotion cream, ophthalmic preparation.
The remaining 75 per cent which constitute the critical drug need represents the gaps products from other countries are filling. The good news is that we have crude oil which can provide the primary base for a new phase in our drug manufacturing initiative when harnessed.
What is your take on the N200 billion Pharmaceutical Development Fund?
We appreciate the 200 billion naira seed money for the pharmaceutical development and hope this will be followed with policies that seek to encourage manufacturing. The fund which is to be offered to manufacturers as a revolving loan at a reasonable interest rate will no doubt assist in boosting local capacity utilization and assist some companies to meet the requirement for World Health Organisation (WHO) pre qualification.
Another point that we need to quickly appreciate is that Nigeria is yet at the most rudimentary stage of our drug manufacturing initiatives. Nigeria is but only a spectator in the 41 billion naira global biotechnology industry. This should prompt government to quickly recognise the role of research and development as an important driver in the growth of the local pharmaceutical industry.
What has PSN being doing to eradicate quacks in the industry?
The level of quackery in Nigeria calls for a concerted effort by stakeholders and government to draw out a plan to tackle the menace. At PSN, we constantly remind government and the regulatory authorities of the apparent danger that Nigerians are exposed to as a consequence of counterfeiting.
PSN also interacts with regulatory agencies giving and receiving information about the status of drugs used in healthcare. The Society also issues alerts through our anti Counterfeiting Task Force, which educates practitioners and the public on the quality of drugs in circulation. The golden rule to the general public is to ensure that they source all their drug needs through registered pharmaceutical premises which are the only legal outlets for sourcing drugs.
What is the way forward for the industry in 2012?
Our vision for the Nigerian pharmaceutical sector remains the attainment of self sufficiency in the supply of quality, safe and affordable drug to Nigerian and exploiting the potential markets and opportunities that the ECOWAS region represents.
We are excited at the prospects of about six of our manufacturers getting prequalified by the World Health organization (WHO), and this we believe will open a new vista in our drug manufacturing efforts.
We are aware that as we speak of local manufacturing of drug, a greater percentage of the active ingredients for the local initiatives are all imported, and this is why we call for the creation of a pharmaceutical commission to drive Nigeria’s journey toward local manufacturing of pharmaceuticals replicating the giant strides that China and India has made in these areas.
---------------------------
BIOTECH:
Onyx Pharmaceuticals And Bayer HealthCare Restructure Global Oncology Partnership
October 13, 2011
Settlement in Litigation Reached
Recently Onyx Pharmaceuticals, Inc. and Bayer HealthCare restructured their partnership for the global development and marketing of Nexavar (sorafenib) tablets and entered into a new agreement related to regorafenib, a late-stage oncology compound.
Under the terms of the agreements, regorafenib is a Bayer compound, and Bayer will have the final decision-making authority for global development and commercialization. Onyx will receive a royalty on any future global net sales of regorafenib in oncology. In addition, Bayer will contract the Onyx sales force to promote regorafenib, along with Bayer sales representatives, in the United States.
The status of Nexavar under the revised Collaboration Agreement remains largely unchanged. Onyx and Bayer are free to use their respective Nexavar sales forces to promote regorafenib and additional products outside of the collaboration in the future. Bayer will purchase Onyx's royalty rights for sales of the product in Japan in exchange for a one-time payment to Onyx. Bayer will have no obligation to pay Nexavar royalties to Onyx on Japanese sales after December 31, 2011. Further, in the event of a change of control or acquisition of Onyx, the current profit-sharing, co-development and U.S. co-promotion of Nexavar will be preserved.
"These new agreements strengthen the collaboration and provide Onyx the opportunity to participate significantly in the market potential of regorafenib," said N. Anthony Coles, M.D., President and Chief Executive Officer of Onyx Pharmaceuticals. "Together we are taking our collaboration to the next level by more effectively structuring our future working relationship. Onyx and Bayer are committed to benefitting patients worldwide and ensuring that the potential of both Nexavar and regorafenib is fully realized."
"These agreements set the stage for the next chapter in our successful partnership," said Dr. Joerg Reinhardt, Chairman of the Bayer HealthCare Executive Committee. "Innovation is central to Bayer's mission 'Science for a Better Life,' and our ongoing collaboration with Onyx demonstrates the priority we place on working with partners to identify, develop and commercialize new medicines to meet unmet or under-served medical needs."
These agreements also settle and dismiss all claims related to the complaint filed by Onyx against Bayer Corporation and Bayer A.G. in the U.S. District Court (Case No. CV09-2145 MHP).
About Regorafenib
Regorafenib is an oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases (TK) currently being investigated in clinical trials for its potential to treat patients with various tumor types.
Regorafenib is an investigational agent and is not approved by the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA) or other Health Authorities.
About Nexavar
Nexavar is approved in the U.S. for the treatment of patients with unresectable liver cancer and for the treatment of patients with advanced kidney cancer. Nexavar inhibits both the tumor cell and tumor vasculature. In preclinical studies, Nexavar has been shown to inhibit members of two classes of kinases thought to be involved in both cell proliferation (growth) and angiogenesis (blood supply) – two important processes that enable cancer growth. These kinases included Raf kinase, VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-B, KIT, FLT-3 and RET.
Nexavar is currently approved in more than 100 countries.
Nexavar is also being evaluated by the companies, international study groups, government agencies and individual investigators.
Important Safety Considerations For Patients Taking Nexavar
NEXAVAR in combination with carboplatin and paclitaxel is contraindicated in patients with squamous cell lung cancer. Nexavar may cause fetal harm when administered to a pregnant woman. Women of childbearing potential are advised to avoid becoming pregnant and female patients should also be advised against breast-feeding while receiving Nexavar.
Cardiac ischemia and/or myocardial infarction may occur. Temporary or permanent discontinuation of Nexavar should be considered in patients who develop cardiac ischemia and/or myocardial infarction. Gastrointestinal perforation was an uncommon adverse reaction and has been reported in less than 1% of patients taking Nexavar.
Uncommon but serious adverse reactions including keratoacanthomas/squamous cell cancer of the skin and Stevens –Johnson Syndrome have been reported in clinical trials.
An increased risk of bleeding may occur following Nexavar administration. If bleeding necessitates medical intervention, consider discontinuation of Nexavar. Hypertension may occur early in the course of treatment. Monitor blood pressure weekly during the first 6 weeks and periodically thereafter and treat, as required.
Hand-foot skin reaction and rash are common and management may include topical therapies for symptomatic relief. In cases of any severe or persistent adverse reactions, temporary treatment interruption, dose modification, or permanent discontinuation of Nexavar should be considered. Temporary interruption of Nexavar therapy is recommended in patients undergoing major surgical procedures.
Elevations in serum lipase and reductions in serum phosphate of unknown etiology have been associated with Nexavar. Caution is recommended when administering Nexavar with compounds that are metabolized/eliminated predominantly by the UGT1A9 pathway, UGT1A1 pathway (eg, irinotecan), doxorubicin, docetaxel, fluorouracil, and substrates of CYP2B6 and CYP2C8, and CYP3A4 inducers.
Concomitant use of carboplatin and paclitaxel with sorafenib resulted in an increase in paclitaxel exposure and an increase in Nexavar exposure. Patients taking concomitant warfarin should be monitored regularly for changes in prothrombin time, INR, or clinical bleeding episodes. Nexavar exposure decreases when co-administered with oral neomycin. Effects of other antibiotics on Nexavar pharmacokinetics have not been studied.
Most common adverse reactions reported for Nexavar-treated patients vs placebo-treated patients in unresectable HCC, respectively, were: diarrhea (55% vs 25%), fatigue (46% vs 45%), abdominal pain (31% vs 26%), weight loss (30% vs 10%), anorexia (29% vs 18%), nausea (24% vs 20%), and hand-foot skin reaction (21% vs 3%). Grade 3/4 adverse reactions were 45% vs 32%.
Most common adverse reactions reported for Nexavar-treated patients vs placebo-treated patients in advanced RCC, respectively, were: diarrhea (43% vs 13%), rash/desquamation (40% vs 16%), fatigue (37% vs 28%), hand-foot skin reaction (30% vs 7%), alopecia (27% vs 3%),and nausea (23% vs 19%). Grade 3/4 adverse reactions were 38% vs 28%.
During postapproval use of Nexavar, the following adverse drug reactions have been identified: angioedema and drug-induced hepatitis, including reports of hepatic failure and death.
For information about Nexavar including U.S. Nexavar prescribing information, visit www.nexavar.com or http://www.onyx-pharm.com/wp-admin/post.php?post=3684&action=edit (http://www.onyx-pharm.com/wp-admin/post.php?post=3684&action=edit).
About Onyx Pharmaceuticals, Inc.
Onyx Pharmaceuticals, Inc. is a biopharmaceutical company committed to improving the lives of people with cancer. The company, in collaboration with Bayer HealthCare Pharmaceuticals, Inc., is developing and marketing Nexavar (sorafenib) tablets, a small molecule drug that is currently approved for the treatment of liver cancer and advanced kidney cancer. Additionally, Nexavar is being investigated in several ongoing trials in a variety of tumor types. Beyond Nexavar, Onyx has established a development pipeline of anticancer compounds at various stages of clinical testing, including carfilzomib, a next generation proteasome inhibitor, that is currently being evaluated in multiple clinical trials for the treatment of patients with relapsed or relapsed/refractory multiple myeloma and solid tumors. For more information, visit www.onyx-pharm.com.
About Bayer HealthCare
The Bayer Group is a global enterprise with core competencies in the fields of health care, nutrition and high-tech materials. Bayer HealthCare, a subgroup of Bayer AG with annual sales of EUR 16.9 billion (2010), is one of the world's leading, innovative companies in the healthcare and medical products industry and is based in Leverkusen, Germany. The company combines the global activities of the Animal Health, Consumer Care, Medical Care and Pharmaceuticals divisions. Bayer HealthCare's aim is to discover and manufacture products that will improve human and animal health worldwide. Bayer HealthCare has a global workforce of 55,700 employees (Dec 31, 2010) and is represented in more than 100 countries. For more information, visit www.bayerhealthcare.com.
SOURCE: Onyx Pharmaceuticals And Bayer HealthCare
Accelerating Pharmaceutical Innovation
Source: Siemens Industry, Inc.
Description
________________________________________
Siemens is using its considerable experience in the application of Process Analytical Technology (PAT) in industries such as food and beverages and the chemical industry to help accelerate change in pharmaceutical manufacturing. With the launch of the Sipat software suite, Siemens is applying its expertise to assist pharmaceutical companies in their implementation of PAT.
Regulatory and financial forces are pushing pharmaceutical manufacturing toward rapid change. PAT represents an exceptional opportunity for pharmaceutical companies to improve manufacturing performance, reduce manufacturing costs, reduce time to market, and improve supply chain responsiveness. PAT allows companies to design quality into the process and move to real-time product release.
The scope for process improvement in many aspects of pharmaceutical manufacturing is considerable. The US Food and Drug Administration (FDA) has noted that the potential worldwide cost savings from efficiency improvements could be as high as US $90B, which is equivalent to the cost of developing 80 to 90 new drugs every year.
The pharmaceutical industry has been slow to adopt PAT in the past, in large part because regulation based on off-line batch inspection slowed progress toward more innovative continuous in-line manufacturing. Now, however, the regulatory landscape has changed. The FDA is engaged in a major drive to encourage the spread of PAT as part of its quality initiatives and cGMPs (current Good Manufacturing Practices) for the 21st century. The FDA's PAT guidance emphasizes the agency's belief that significant opportunities exist for improvement and innovation in pharmaceutical manufacturing by moving from empirically derived trial-and-error methods to rigorous mechanistically based and statistically controlled processes.
----------------
Biotech company IRX moves from NY to FL
AP – Thu, Oct 20, 2011
ST. PETERSBURG, Fla. (AP) — Biotechnology company IRX Therapeutics Inc., which makes treatments for cancer and infectious diseases, said Thursday that it is moving to St. Petersburg, Fla., eventually adding about 280 jobs.
IRX, which is relocating from New York City starting at the end of the year, has already licensed a broad patent portfolio from the University of South Florida, where early technology was developed. Under a letter of intent signed by the parties involved, IRX and the Florida High Tech Corridor Council will fund $2.5 million in research to be performed at USF for developing therapeutic vaccines and clinical trials.
"This is exactly what ought to be happening in St. Pete and in Florida," said Gov. Rick Scott, who attended the announcement. "Florida is second in the nation in biotech research facilities."
IRX has raised $90 million in capital for research, manufacturing and clinical development. The company's lead product, IRX-2, is an active immunotherapy designed to treat cancer by restoring the patient's immune system and enabling an immune attack on tumors.
IRX will initially employ 40 people and within five years intends to fill more than 280 positions with an anticipated average salary of more than $90,000 — more than double the average wage in Pinellas County. Those figures don't include additional jobs that will be created for commercial-scale manufacturing and a potential product launch.
The relocation package, approved at state and local levels, includes $600,000 from the state's innovation fund; $275,000 from Pinellas County Economic Development; a $275,000 credit toward land owned by the City of St. Petersburg; and $50,000 from the USF Research Foundation. All cash incentives will be repaid by IRX as the company meets specified revenue targets.
"It is a great day in St. Petersburg," said Rick Baker, a USF vice president who led the effort to bring IRX to Florida. The successful effort helps USF's stature as a major research facility as well as an asset to the local economy, he said.
John W. Hadden II, CEO of IRX, called USF "an outstanding partner" in his company's progress.
"It's not just jobs here," he said. "We lead the world in biotechnology, and we will continue to be competitive internationally."
