Chemotalk Newsletter

Chemotalk Newsletter, Vol. 50: June 1, 2012

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Hi, Everybody ...

I found this almost accidentally, but it's worth reading. From Science News ...


Australian researchers are calling for the open sharing of clinical trial data in the medical research community, saying it would be instrumental in eliminating bottlenecks and duplication, and lead to faster and more trustworthy evidence for many of our most pressing health problems. Moreover, hackers should be role models for freeing up access to the "source code" of clinical trials -- patient-level data -- the researchers from the University of New South Wales (UNSW) argue in a commentary published in the journal Science Translational Medicine.

Hackers revolutionized the software industry by countering the economic and cultural motivations that drove closed source software and disengagement from user needs. "Similar roadblocks plague the clinical evidence domain where, despite a rapid increase in the volume of published research, physicians still make decisions without access to the synthesized evidence they need," said paper co-author, UNSW Australian Institute of Health Innovation Research Fellow, Dr Adam Dunn.

The call follows a wider push for free, open access to academic publications and intellectual property rights designed to turn more university research into real-world applications. Open source communities often out-perform their closed source counterparts, most notably in the software community where millions of programmers contribute code that can be used for free, by anyone.

"If the same principles were applied to medical research, bottlenecks, biases and self-interest would be largely removed," said Professor Enrico Coiera, a co-author on the paper along with UNSW Professor Rick Day, and Professor Kenneth Mandl from Harvard Medical School.

"Clinical trial data is a potential goldmine. If researchers, doctors and patients were able to re-analyse and pool this data, there would be a host of questions that could start to be answered. But these meta-analyses are very uncommon because researchers and companies don't like to share data," Professor Coiera said. "One solution, which has no support, is for data to be pirated. No one would win in that scenario. But everyone could be a winner if clinical research data went open source."

While there are technical challenges around building an open source community for clinical trials, including important considerations around privacy and data quality, "these could be easily overcome," Dr Dunn said.

Less easy to overcome are the social and financial barriers. "Most researchers want to hold their data as long as they can as the basis for publications," Dr Dunn said. "And unfortunately, pharmaceutical companies want to control the messages that are delivered to doctors and maximize profits rather than facilitate the cost-effective delivery of care."

The research was supported by Australia's National Health and Medical Research Council and the US-based National Library of Medicine.

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Last month's (Vol. 49) Newsletter had some promising information about nanoparticles. Here's another, slightly different application that's working, at least in lab settings (raising the burning question: How long before it gets to us?)


Researchers at Northwestern University are touting some positive results for an inventive drug delivery method: Gold-crafted, star-shaped nanoparticles that get deep into CANCER cells to unload treatment.

Here's how it works: The gold nanostars are loaded with the DNA aptamer AS1411 and injected into the body. Once there, they bind with nucleolin, a protein found on the surface of cancer cells. Then, as the cell draws the needed nucleolin toward its nucleus, the nanostars essentially trick the cancerous cells into letting them in, and, with a burst of light delivered by the researchers, the particles break up to deliver the aptamer and harm the cell.

The researchers studied the method's effectiveness on human CERVICAL and OVARIAN cancer cells, and they found the method contributes to a deformation of cancer cells' nuclei. The process can lead to cells dying and failing to reproduce.

Other nano cancer treatments have to deal with penetrating tumor cells, which requires passing through the nuclear membrane and thus crafting nanoparticles of certain size and shape. This Trojan Horse method does away with all that, and because Northwestern's nanostars get a nuclear welcome mat, they can be fairly large (for nanoparticles, that is) and loaded with a bigger drug payload.

After the initial tests, researchers have put their method up against 12 other cancer cell lines, finding similar results all around. "All cancer cells seem to respond similarly," lead researcher Teri Odom explained, as quoted by 'Futurity'. "This suggests that the shuttling capabilities of the nucleolin protein for functionalized nanoparticles could be a general strategy for nuclear-targeted drug delivery."

The scientists believe that as the method is developed, it will be particularly handy in fighting cancers close to the skin's surface. These would include SKIN and some BREAST cancers.

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Later this week (week of May 13) the cancer drug research crowd will examine a tsunami of abstracts filed ahead of the ASCO meeting in early June in the hopes of finding a few new gems in the mountain of data being readied for the confab. ASCO is the place where anyone who's doing anything in cancer tries to make a splash in the spotlight. And with CLOSE TO A THOUSAND CANCER DRUGS IN THE PIPELINE, that's no easy task.

Pfizer and Eli Lilly were both out bright and early this morning touting their work in the cancer arena. Pfizer's best hope at drawing attention to its pipeline prospects lies in axitinib, a prospect for RENAL CELL CARCINOMA. And Lilly clearly hopes to impress analysts with ramucirumab, which is in 6 late-stage cancer studies. Digging deeper, recent take on the top 10 cancer drugs in late-stage studies includes some of the closest watched therapies likely to elbow their way to center stage. Aveo will be working hard to distinguish tivozanib--its KIDNEY CANCER drug with so-so head-to-head data with Nexavar--as it takes a monumentally important run at an approval later this year. Anything new on Roche's T-DM1 for BREAST CANCER, which has racked up positive late-stage data on breast cancer on its way to an odds-on approval at the FDA, will be studied closely. Onyx has the promising carfilzomib to tout, which is already at the FDA for review, while regorafenib is also in the media mix. One savvy biotech scribe assesses 8 drugs likely to make it into the center ring at ASCO.

In addition to the drugs already mentioned, the list includes abiraterone from Johnson & Johnson and Exelixis's cabozantinib, a promising cancer drug that has earned Exelixis CEO Mike Morrissey both acclaim and exceptionally harsh criticism. The development program for cabo has been raked over the coals by a number of analysts. Medivation's enzalutamide, meanwhile, could wind up stealing the thunder for PROSTATE CANCER. And there's follow-up data from Ariad on ponatinib.

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Pfizer took one step closer to an FDA approval of a potential blockbuster. An FDA advisory committee on Thursday endorsed the company's drug, tofacitinib, as a safe and effective treatment for patients with RHEUMATOID ARTHRITIS.

Yet there are plenty of doubts about whether the agency will take the recommendation. The Arthritis Drug Advisory Committee voted 8-2 in favor of approval of the experimental arthritis pill, which could become the first disease-modifying oral drug against the autoimmune disorder in more than a decade and the first JAK inhibitor to hit the U.S. market for this disease, according to Pfizer. The company has asked for approval for the drug as a second option for the thousands of RA patients who don't respond to existing injectable meds such as Humira and Enbrel.

The FDA action date for the application is in August. Pfizer has a lot riding on the approval of tofacitinib. The U.S. drug giant has lost exclusivity for the mega-blockbuster Lipitor, U.S. sales of which fell by 71% in the first quarter. Tofacitinib is among a handful of prospects in the company's pipeline that could bring more than $1 billion in annual sales and help replace declines in Lipitor revenue. Several analysts estimate sales of the drug to hit $1 billion or more by 2015 if approved this year.

Yet the FDA could spoil Pfizer's blockbuster plans for the drug. The agency's staff reported this week that there were more cases of CANCER and infections in patients who took the drug in studies, and they noted that the X-ray method used to measure the impact of the drug on patients' disease wasn't sufficient for the agency to judge the efficacy of the treatment. However, the arthritis panel of non-agency experts voted unanimously that the efficacy of the drug was sufficient for approval.

"The committee ultimately viewed the safety profile of tofacitinib as acceptable; however, several panelists suggested that tofacitinib should be approved for use in patients who have failed other available treatment options, including anti-TNF inhibitors," said analysts at Cowen. "We continue to expect tofacitinib to be approved in aTNF-refractory patients for whom there is still a great unmet medical need."

Pfizer has plenty of opponents in race to develop new oral RA meds. Behind Pfizer, Eli Lilly and Incyte are developing a rival JAK inhibitor for treating RA, and AstraZeneca and Rigel are in late-stage development of an oral med to combat the disease.

Pfizer was predictably upbeat about its own program after the panel's nod. "We are pleased with the Committee's positive evaluation of the tofacitinib data and its decision to recommend approval," Dr. Yvonne Greenstreet, senior vice president and the head of Medicines Development Group for Pfizer Specialty Care, said in a statement. "The RA patient population needs additional treatment options, and Pfizer looks forward to working with the FDA on next steps as it completes its review of the tofacitinib application."

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By Donald G. McNeil, Jr.

A month after his 2000 graduation from Yale Law School, Seun Adebiyi learned he had not one nut two lethal blood CANCERS and began an odyssey to find a bone-marrow donor. Mr Adebiyi, 28, who came to this country from Nigeria as a child, made appeals through Yale, on radio stations, in YouTube video and even on a trip to Nigeria to ask law students to volunteer.

But finally, his doctor called, saying that a Nigerian woman in this country had donated her baby's umbilical cord blood to a "cord-blood bank" and that the stem cells in it were a close enough match. After his own marrow -- the source of his cancers -- was wiped out, those cells were infused into him at Memorial Sloan Kettering Cancer Center. He has been in remission since.

Now he is trying to repay that debt, with an effort that experts say may save the lives of both Nigerians and black Americans. In February, he helped start Nigeria's national bone-marrow registry, the first in Africa outside South Africa. He is now raising money to start a cord-blood bank there.

Millions of Nigerians have blood cancers like LEUKEMIA or LYPHOMA, and about 4,000 black Americans die annually of them. Less than 20% of black Americans now find the perfect donor matches that could save their lives, while more than 70% of whites do. Without a registry and cord-blood bank, no Nigerians do. "This is a slam-dunk, from my point of view," Mr Adebiyi said. "The U.S. registries are trying to figure out how to increase the population of minority donors; this is a solution they should be interested in."

Becoming a donor is relatively simple nowadays; only a cheek swab is needed to test for a match. Donating rarely requires the painful hip punctures that used to be routine Instead, an intravenous blood line runs through a cell separator after the donor takes drugs to push the stem cells into the bloodstream The process is no more burdensome than dialysis, experts say.

But for African-Americans like Mr. Adebiyi, finding matches is particularly difficult. Blacks are less likely to register as donors; while blacks are 12.6% of the population, only 8% of registered donors are black.

"It's lack of education about it, and mistrust of the medical system after scandals like Tuskegee," said Shauna Melius, co-founder of Preserve Our Legacy, citing the Tuskegee, Ala., experiment in which government doctors recruited black farmers for research and let those with syphilis go untreated to decades. Her organization recruits donors at Harlem Hospital and through dries featuring black celebrities.

"Plus," she added, "people are skeptical because you're collecting DNA."

Complicating the problem, blacks are more genetically diverse than whites. Anatomically modern Homo sapiens existed in Africa for 200,000 years before migrating north to Europe a little over 40,000 years ago, so all Europeans descend from the shallower end of the gene pool.

Although no expert would predict 4exactly how many American lives could be saved, because there are so many variables, several suggested that dozens of cancer patients would benefit -- and some of the 1,000 Americans a year who face life-threatening sickle-cell disease could potentially be cured as well. "It could be useful to everybody to have a lot more people lined up as donors, " said Dr Harold Varmus, director of the National Cancer Institute. "And it could help recruit minority Americans if you could point out that folks in Africa are signing up too."

Dr. Willis Navarro, medical director for the National Marrow Donor Program, called Mr. Adebiyi's plan "amazing." Susan L. Solomon, chief executive of the New York Stem Cell Foundation, said it was "a really big deal."

Because most African-Americans are descended from slaves from West Africa, a donor pool there will help, said Dr. Pablo Rubinstein, co-founder of the national cord-blood program at the New York Blood Center.

Nigeria has 154 million people and more than 400 ethnic groups

It will particularly help those with more African genes. Most black Americans have some white ancestors and, on average, 35% European genes, but individuals vary widely.

Umbilical cord blood is even more useful than bone marrow, because its stem cells are "more tolerant," Dr. Rubenstein said. They have survived fewer bacterial and viral assaults and are less likely to counterattack with graft-versus-host disease.

Before cord blood became common in the 1990s, blacks almost never found matches. "In 1990, we only found six matches for African-Americans, and all of them had typical European genes," Dr. Rubenstein said

Mr. Adebiyi found out he had both lymphoblastic lymphoma and stem cell leukemia when he was working at Goldman Sachs. He had no full siblings to donate marrow and as his search for a matching donor in the United States led nowhere, he said, "I realized that my only chance was within my own ethnic group in Nigeria." He flew there and spoke to 300 law students. Most agreed to have their cheeks swabbed, "and I carried the saliva back with me on the plane," he said.

But before the testing was done, the cord match turned up.

Back in 2003, he missed making Nigeria's 2004 Olympic swim team by 0.12 seconds. Now, while on temporary disability retirement from Goldman because of the neurological effects of his CHEMOTHERAPY, he is trying for the 2014 Winter Games in the skeleton luge, which flings competitors headfirst down an icy track. He has no Nigerian rivals, but he still has to make minimum qualifying times to compete. (And yes, he said, one of his coaches did train Jamaica's famous bobsled team.)

He has spent $32,000 of his own Goldman money on computers and software for Nigeria's donor registry. The University of Nigeria's medical school does the DNA testing. He is now trying to raise enough to start the cord-blood bank. It needs liquid nitrogen storage and backup generators. Ideally, the operation would also have at least two apheresis machines, which extract stem cells from blood, so Nigerians would not have to travel to South Africa or London to donate. All together, he estimates, it could be started for $75,000 and in total would cost less than $300,000.

Nigeria's national bone marrow registry officially opened February 24 with donations from several hundred medical, nursing and laboratory science students. Two University of Nigeria medical professors are donating their time as administrators.

Ultimately, the program should be able to support itself easily, Mr. Adebiyi argued, because American insurers commonly reimburse registries up to $35,000 for the costs of finding the donor and extracting the cells.

Direct payments to donors are illegal under American law, there is no Nigerian law yet. Mr. Afdebiyi said he would not mind donors being paid modest fees.

Dr. Ifeoma Okoye, a radiologist and one of the administrators, said cord blood should be easy to get, given Nigeria's high birthrate. "There used to be cultural superstition around the cord, and families would demand it be buried," she said. "But that practice is no longer held on to. We dispose of cords as medical waste every day in our hospital."

The administrators are aware that large reimbursements from Western insurance companies could make cord-blood banking a tempting target for corruption, which is endemic in Nigeria. To reduce that temptation, said Dr. Sunday Ocheni, another administrator, the bank will be registered as a nonprofit organization.

Mr Adebiyi said he did not intend to ask for even a salary. "I personally don't plan to accept a penny from this; I've already been paid," he said referring to the donation that saved his life.

"It's unfortunate that someone just as deserving of life as me might die when the cure might be in the woman sitting next to them on the bus."

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Finally, a bit of politics.

If this is happening in California, it's happening everywhere. There's a proposition on the primary ballet in California, to gather extra taxes from smokers and use it for cancer research. The majority of political ads in the Los Angeles market are about this measure, and most of them are against it. Their ad argues that somehow, the passage of this proposition would support jobs out of state -- as though cancer patients - or anyone else, for that matter - cares which state comes up with a cure. In case you haven't figured it out who wants to kill this legislation, it's the tobacco companies. They have the megabucks to buy an ad schedule on every channel (and probably radio, too) that dominates the conversation. So beware, if they're not working against cancer research in your state at the moment, Big Tobacco will be there as soon as taxing smokers become an issue.

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Until next month ...

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And if you have any thoughts of how this newsletter could be improved, please email me directly, at

Elaine Jesmer

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