Dow AgroSciences receives first country registration for Sulfoxaflor from Korea

Singapore, Nov 23, 2011: Dow AgroSciences, a wholly owned subsidiary of The Dow Chemical Company, announced that it has received the first country registration for the sulfoxaflor molecule. Consistent with the outcome of the recent scientific review of sulfoxaflor at the Joint FAO/WHO Meeting on Pesticide Residues (JMPR), the Korean regulatory agency has announced its decision to register the product for use on apples, pears, and red peppers. This important first registration keeps the global sulfoxaflor molecule on-track for launch during the first half of 2012. “Sulfoxaflor will provide farmers an effective solution against sap-feeding insects that are destructive to a wide range of crops including cotton, tree fruits, vegetables and rice,” said Mr Tim Hassinger, Global Leader, Agricultural Chemicals, Dow AgroSciences. “This first registration of sulfoxaflor is an important step in the regulatory journey for this molecule and a critical element of our company’s growth strategy.” Sulfoxaflor is the first molecule to be commercialized from the new sulfoximine class of insecticides developed by Dow AgroSciences. Effective at low use rates with fast-acting control, sulfoxaflor addresses a $2 billion global market segment where needs are currently unmet with existing technologies. Sulfoxaflor is not yet registered with the U.S. Environmental Protection Agency. Federal registration is pending.

Transgene Biotek to sell technology for Recombinant Human Erythropoietin for $5 million

Mumbai, Nov 23, 2011: Transgene Biotek, has announced the sale of technology for recombinant human Erythropoietin (rh-EPO) to TSS EXPORT GmbH FZE, one of the group companies of the TSS Group for US$5.0 million. The technology transfer and sale of this technology is expected to be completed during a period of approximately 5-6 months. Transgene Biotek Ltd has made headlines in recent years for having out-licensed two of its technologies - including a recombinant Hepatitis B Vaccine to one of the largest vaccine producers in the world, and more recently Orlistat to one of the biggest Indian pharma companies with a significant presence on the global arena. Speaking about the transaction Dr K.K.Rao, Managing Director, Transgene Biotek Limited said “This transaction fulfills the pledge we made earlier this year to focus on revenue generation whilst monetizing the sale of underutilized Bio-generic drug assets; those developed by the company during the last 7-8 years but which we now feel do not fit into our new agenda for sustained growth” The company recently commenced commercial manufacturing operations of DHA, an Omega-3 Fatty acid which in recent years has witnessed explosive growth in the nutraceuticals and health supplements market. Whilst currently manufacturing in leased facilities, Transgene is also in the process of expanding its own in-house infrastructure to augment production capacities for this and other APIs coming into production. Within weeks Transgene also expects to begin the commercial manufacturing of a second API, Tacrolimus. Both APIs are being aimed at non-regulated markets. At the same time the company’s management is in talks with a number of manufacturers in Europe and North America for strategic partnerships (or JV’s) to manufacture and distribute these products into regulated markets. Founded in 1991 by Dr Koteswara Rao, Transgene Biotek Ltd was one of the first pure bred Biotechnology companies in India.. The company’s first major success came in 1999 when Transgene sold its proprietary genetically engineered recombinant Hepatitis B vaccine technology to the Serum Institute in Pune who continue to sell vaccines based on the same technology even today.

First Dogs Came from East Asia, Genetic Study Confirms

Dr Peter Savolainen, KTH researcher in evolutionary genetics, says a new study released Nov. 23 confirms that an Asian region south of the Yangtze River was the principal and probably sole region where wolves were domesticated by humans.

Data on genetics, morphology and behaviour show clearly that dogs are descended from wolves, but there's never been scientific consensus on where in the world the domestication process began. "Our analysis of Y-chromosomal DNA now confirms that wolves were first domesticated in Asia south of Yangtze River -- we call it the ASY region -- in southern China or Southeast Asia," Savolainen says.

The Y data supports previous evidence from mitochondrial DNA. "Taken together, the two studies provide very strong evidence that dogs originated in the ASY region," Savolainen says.

Archaeological data and a genetic study recently published in Nature suggest that dogs originate from the Middle East. But Savolainen rejects that view. "Because none of these studies included samples from the ASY region, evidence from ASY has been overlooked," he says.

Peter Savolainen and PhD student Mattias Oskarsson worked with Chinese colleagues to analyse DNA from male dogs around the world. Their study was published in the scientific journal Heredity.

Approximately half of the gene pool was universally shared everywhere in the world, while only the ASY region had the entire range of genetic diversity. "This shows that gene pools in all other regions of the world most probably originate from the ASY region," Savolainen says.

"Our results confirm that Asia south of the Yangtze River was the most important -- and probably the only -- region for wolf domestication, and that a large number of wolves were domesticated," says Savolainen.

In separate research published recently in Ecology and Evolution, Savolainen, PhD student Arman Ardalan and Iranian and Turkish scientists conducted a comprehensive study of mitochondrial DNA , with a particular focus on the Middle East. Because mitochondrial DNA is inherited only from the mother in most species, it is especially useful in studying evolutionary relationships.

"Since other studies have indicated that wolves were domesticated in the Middle East, we wanted to be sure nothing had been missed. We find no signs whatsoever that dogs originated there," says Savolainen.

In their studies, the researchers also found minor genetic contributions from crossbreeding between dogs and wolves in other geographic regions, including the Middle East.

"This subsequent dog/wolf hybridisation contributed only modestly to the dog gene pool," Savolainen explains.

FDA Review On Transgenic Salmon Too Narrow, Experts Say

The salmon, whose genome contains inserted genes from two other fish species, could become the first genetically modified animal approved for human consumption in the United States.

The FDA held two days of hearings in September to assess the fish's human and environmental health risks. The period for public comment ends this month. A final FDA decision could be imminent.

The concern, Duke economist Martin D. Smith says, is that the new animal drug application process FDA is using to review the transgenic salmon evaluates its safety only by comparing its nutritional profile to an equivalent portion of nonmodified salmon, and screening it for known toxins and allergens.

Smith said such a process ignores the potential health and environmental effects of salmon production and consumption -- both positive and negative -- that might stem from the fish's faster growth and less need for feed.

"These market impacts could dwarf any small differences in nutritional content," says Smith, associate professor of environmental economics at Duke's Nicholas School of the Environment.

A smarter approach, Smith and his coauthors argue, would be for FDA -- or if necessary, Congress -- to broaden the interpretation of the terms "safe" and "health" in FDA statutes so its review process can include an evaluation of the overall safety of the new fish compared to other protein sources that it might replace, such as beef.

"Instead of focusing on the safety of a food taken one portion at a time or whether it was produced through genetic modifications or through classic breeding, a more useful approach would be to evaluate whether society is better off overall with the new product on the market than without it," says Jonathan B. Wiener, William R. and Thomas L. Perkins Professor of Law at Duke Law School.

This fuller assessment would require FDA regulators to take into consideration factors currently unaccounted for, such as public health impacts that could occur if, as is likely, increased production of transgenic farmed salmon leads to lower retail prices and increased consumption.

"Lower prices for salmon would have significant public health benefits," Smith explained. "Consumers would have access to a less expensive source of healthy protein and omega-3 fatty acids, which have well-documented health benefits."

A broader review would also allow a fuller assessment of potential environmental impacts, such as pollution from farmed salmon waste; disease; increased harvesting of the wild fish used to feed farmed salmon; and the escape of genetically modified salmon into the wild, where they could affect wild salmon stocks through gene transfer or increased competition for resources.

The National Environmental Policy Act mandates FDA to assess significant environmental impacts from market expansion of the products it approves, yet the narrow scope of the current review process for new animal drugs presents "an incomplete picture" of these risks and benefits for transgenic salmon, the researchers write in their analysis.

"The approval of genetically modified salmon will set an important precedent for other transgenic animals intended for human consumption," Smith says. "It's essential that FDA establishes an approval process that assesses the full portfolio of impacts to ensure that such decisions serve society's best interests." FDA administrators need to weigh the benefits of such assessments against the costs and delays they likely would incur, he says.

If conducting a full assessment of transgenic salmon would take too long, a reasonable compromise would be to use existing studies to develop scenarios of market growth and the broader impacts to human and environmental health that may occur as a result.

Frank Asche of the University of Stavanger, Norway, and Atle G. Guttormsen of the Norwegian University of Life Sciences co-authored the Science paper with Smith and Wiener.

Risks Involved With Transgenic Fish

One of the locations where Fredrik Sundström's studies were conducted was in an artificial stream where microchips were used to documented the movements of the fish. (Credit: Photo courtesy of Lars-Erik Sundström)

"Until further notice transgenic fish should be bred in closed systems on land," says Fredrik Sundström at the Department of Zoology, University of Gothenburg, Sweden.

By furnishing fish with genes from other organisms, so-called transgenes, researchers have succeeded in producing fish that grow considerably faster or are more resistant to diseases. Fish can also be modified to cope better with cold, which facilitates breeding in colder conditions. There are major benefits for commercial fish farming as transgenic fish are expected to deliver higher production and better yields. However, transgenic fish can also entail risks and undesirable effects on the natural environment.

More resistant to toxins

For example, transgenic fish can be more resistant to environmental toxins, which could entail the accumulation of toxins that ultimately end up in consumers. There are also misgivings that the higher level of growth hormone in the fish can affect people. Researchers at the University of Gothenburg have therefore been commissioned by the EU to study the environmental effects of GMO (genetically modified organisms) within fish farming. The results of the studies show that the genetically modified fish should be treated with great care.

Simulated escapes

Sundström, PhD at the Department of Zoology, has studied transgenic salmon and rainbow trout to ascertain what ecological risks they might constitute for the natural environment. The study, which simulated escapes in a laboratory environment, shows that transgenic fish have a considerably greater effect on the natural environment than hatchery-reared non-transgenic fish when they escape. For example, genetically modified fish survive better when there is a shortage of food, and benefit more than non-transgenic fish from increasing water temperatures.

"It is probably due to the fact that genetically modified fish have a greater ability to compete and are better at converting food," says Sundström.

Natural breeds are under threat

If transgenic fish become established in natural stocks they would be able to outcompete the natural breeds. However, conducting studies in a laboratory environment that imitates nature is complicated, which makes it difficult to predict how escaped transgenic fish affect the natural environment. Sundström's conclusion is that international consensus is required before commercial farming can be permitted, and that a precautionary principle must be applied.

"One option is to farm the transgenic fish on land, which would make escape impossible. At least fertile fish should be kept in a closed system," says Sundström.

As of yet no country has permitted commercial farming of transgenic fish, but several applications for such operations are under consideration by authorities in both the USA and the EU

Mutants With Heterozygote Disadvantage Can Prevent Spread of Transgenic Animals

These new findings may help to achieve greater safety when conducting release experiments involving genetically modified animals.

Genetically modified organisms must not be allowed to spread uncontrollably. Scientists are therefore keen to take advantage of a mechanism that will localise the spread of mutants. Mutants with a heterozygote disadvantage, as it is known, reduce the evolutionary fitness of their carriers to varying degrees if they are only available to one gene copy (heterozygote) or exist in both gene copies (homozygote). In their study, the Max Planck scientists assumed a fitness loss of 50 percent (compared to wildtypes) for mutant heterozygotes and a 10 percent fitness loss for mutant homozygotes.

A mutant with a heterozygote disadvantage can be maintained in a population if it occurs frequently enough for sufficient homozygote offspring to be produced. Above this value, it can suppress the non-mutated gene variant completely and the mutated form becomes extinct. Populations containing mutants with heterozygote disadvantage develop into one of two stable states. These mutant types therefore seem to be well-suited for the safe release of genetically modified organisms. After all, as soon as sufficient numbers of mutants exist in the environment, these replace the natural variant in a local population. If such genes are joined to resistance genes to combat pathogens, mosquito populations could be rendered resistant to Malaria, for example. By releasing the wildtype at a later stage, the transgenic animals can therefore also be removed again more easily from the environment. In population genetics this is known as underdominance.

The researchers then analyzed computer-based simulations showing the effect of mutants with heterozygote disadvantage on two populations of equal size, which, as in nature, are subject to statistical fluctuations. In doing so, they paid particular attention to the gene flow arising from the mobility of the individuals. At times, such a mutation can survive in a stable state in a population. However, this only happens if the migration rate is less than 5 percent. "Our calculations have also shown that mutants are best released into both populations even if the goal is to establish the new genetic variant in only one of them in the long term. If, for example, 75 percent of transgenic animals are distributed to the target population and the remaining 25 percent to a neighbouring population, the transgenic individuals may find it easier to gain traction on a long-term basis in the target population," explains Philipp Altrock from the Max Planck Institute for Evolutionary Biology.

Scientists in the USA, Brazil, Malaysia and the Cayman Islands have been conducting field experiments on the use of genetically modified animals for several years. These include, for example, experiments involving genetically modified mosquitoes, to protect against infectious diseases such as malaria or dengue fever, and transgenic plant pests. Similar experiments are planned in another nine countries. To date, the males from various insect species, which are generally infertile, are released. In this way, the effective size of the wild population is limited. "One of the disadvantages of this method is that it needs to be repeated very frequently as the transgenic animals cannot reproduce," says Arne Traulsen from the Max Planck Institute in Plön. In addition, in the case of mosquitoes, a few parent individuals can already have a large share of the next generation.

In contrast, mutants with heterozygote disadvantage can survive for many generations. Resistance genes linked to such mutants would therefore be more efficient. The safety aspect also increases, as proliferation across a target population is very unlikely. "Nevertheless, the fitness of the transgenic animals, the population sizes, and the migration rates must be known. These factors can most likely be determined for release experiments on maritime islands," says Arne Traulsen.

A Proposal To Expand Accelerated Approval

Looks like BIO has been reading my previous post.

From Pharmalot, a post describing BIO's lobbying efforts with the Senate and FDA to expand the use of accelerated review in the FDA for drugs to diseases that do not have any approved cures. This would be applied not only to drugs for Orphan conditions but likely to cancers or AIDs drugs as well.

Under accelerated approval, a drugmaker can conduct shorter trials based on the measured effect of the drug rather than on an actual clinical outcome.  Sen. Kay Hagan (NC-Dem) would also ask that Phase II data could be used for drugs where data can't be "ethically, feasibly or practicably generated."

Presumably, this lobbying effort is being done in part as a consequence of criticism that the FDA's approval process has become too unpredictable in these type of clinical areas.  The FDA responded that the agency has approved 85 rare-disease treatments since 2006, and that 75 percent were based on limited clinical trials.

That observation would tend to undermine industry's claims and make them sound as if they are sounding a "false alarm".  Notwithstanding, I would still tend to favor expedited approval on drugs meeting the criteria above if there is also strong post-approval surveilance.  Based on analysis of that data, all parties involved should be willing and prepared to pull drugs from the market that do not live up to their pre-approval performance predictions when exposed to larger patient groups.