BioResearch Compliance Report

The Insider’s Guide to GCP and GLP Compliance & Enforcement

Online Update Page, August 8, 2007


Experimental drugs

Federal court rules against ‘Abigail,’ sees no constitutional right to unapproved drugs 

In a win for FDA’s existing regulatory requirements for access to experimental drugs, the U.S. Court of Appeals for the D.C. Circuit Aug. 7 ruled that terminally ill patients do not have a constitutional right to be treated with experimental drugs, even if they likely will be dead before the medicine is approved.

The ruling by the U.S. Court of Appeals for the District of Columbia Circuit overturned last year's decision by a smaller panel of the same court, which held that terminally ill patients may not be denied access to potentially lifesaving drugs.  That decision emanated from a suite filed against FDA in 2003 by the Abigail Alliance for Better Access to Developmental Drugs and the Washington Legal Foundation, seeking access for terminally ill patients to drugs that have undergone preliminary safety testing in as few as 20 people but have yet to be approved.

The appellate disagreed, saying in an 8-2 ruling that it would not create a constitutional right for patients to assume "any level of risk" without regard to medical testing.

"Terminally ill patients desperately need curative treatments," Judge Thomas Griffith wrote for the majority. But "their deaths can certainly be hastened by the use of a potentially toxic drug with no proven therapeutic benefit."

FDA spokeswoman Susan Cruzan said the agency was pleased with the decision, which she said considered the public's safety and the need for access to experimental drugs.

Abigail Alliance founder Frank Burroughs pledged an appeal to the Supreme Court. Burroughs' daughter, Abigail, was denied access to experimental cancer drugs and died in 2001. The drug she was seeking was approved years later.

"What the opinion by Judge Griffith is saying is, 'We don't want to risk one life or a few lives, even at the expense of the lives of hundreds or thousands of people,'" Burroughs said. "The logic of that escapes me."

In a sharply worded dissent, Judge Judith W. Rogers called the ruling "startling." She said courts have established the right "to marry, to fornicate, to have children, to control the education and upbringing of children, to perform varied sexual acts in private, and to control one's own body even if it results in one's own death or the death of a fetus."

"But the right to try to save one's life is left out in the cold despite its textual anchor in the right to life," Rogers wrote.

Rogers was joined by Chief Judge Douglas Ginsburg. The case cut across party lines, with conservative and liberal judges taking both sides of the dispute.

The court noted that there are government programs that provide access to experimental drugs in certain situations. It said the matter is not closed and said Congress might be a better venue than the courts to address the issue.

Burroughs said he expects such legislation to be introduced this session. Both the Senate and House have considered such legislation but it languished in committee.

Human subject protection

Death in gene therapy trial highlights weaknesses in patient safeguards

A close look at the events leading to the death of 36-year-old Jolee Mohr following her participation in a gene therapy trial reveals failures in procedures designed to protect people from the risks of medical experimentation and in particular, the risks of gene therapy, “The Washington Post” reported Aug. 6.

Mohr died from massive bleeding and organ failure July 24, three weeks after receiving the second injection of an experimental drug made of genetically engineered viruses designed to treat arthritis.

No one knows yet whether the treatment caused Mohr’s death, The Post noted. Of the dozens of other volunteers who got the injections, only Mohr suffered anything more than short-lived side effects, said officials at Targeted Genetics, the Seattle company that makes the product.  FDA and the company are investigating.

However, The Post stated, breaches of clinical research standards and a federal oversight system that allowed key decisions to be made behind closed doors may have helped draw Mohr into an experiment that was not, her husband says, what she thought it was.

“It was presented to her like this is going to make her knee better,” said Robb Mohr, an agronomist who lived with his wife of nine years in a modest vinyl-sided ranch home near Springfield, IL. “It was supposed to be just a simple thing.”

Company officials vigorously defend the study, saying they were upfront about risks, adhered to all regulations and were terribly saddened by the loss. “We’re human,” H. Stewart Parker, Targeted Genetics’ chief executive, told The Post. “This is not just a patient. This is a person, and this is a horrible tragedy.”

A two-sentence paragraph halfway through a 15-page consent document that Jolee Mohr signed warns of the possibility of “unknown side effects,” including, “in rare circumstances, death.”

Further in, after long descriptions of how the product may help, a single sentence states: “We do not expect you to receive any direct medical benefits from participation in this study.”

Mohr was in a Phase I study, the prime goal of which was to see whether the treatment was safe, not to provide a therapeutic benefit.

Her rheumatologist, Robert Trapp, whose Springfield clinic got payments from Targeted Genetics for each subject he recruited, also defended the study. “The theory behind it seemed good, and the science seemed good,” he said. “There’s nothing I knew of that could have predicted this.”

Targeted Genetics was testing tgAAC94, a virus engineered to have an extra gene. Injected into a joint, the virus infects cells and continuously produces proteins that sop up inflammatory molecules, according to the company.

Like other gene therapies -- hundreds of which have been tested since 1990 and all of which are still experimental -- the approach has the potential advantage of having the body crank out its own medicine for months or years after treatment, right where it is needed.

That sounded good to Mohr when Trapp, one of 20 U.S. doctors testing tgAAC94, invited her to join the study on Feb. 12, The Post reported.

Trapp said he thoroughly explained the risks to Mohr, according to The Post

The consent form was approved by a for-profit IRB, according to The Post.  Targeted Genetics noted that the review firm it used is accredited and accepted by FDA. But the use of private boards, as opposed to those run by universities or government agencies, has raised alarms among some medical ethicists since a for-profit review board risks losing repeat business if it is too tough on its clients, The Post stated.

Mohr’s first shot, administered on Feb. 26, had no noticeable effect, and she wondered whether she got the placebo. But she was excited that the next one would be the real thing, Robb Mohr said.

That happened on July 2.  The Post said he recorded her temperature at 99.6, then gave her the shot.

“The next day she woke up and didn’t feel good at all. By afternoon she started vomiting,” Robb Mohr recalled. “By evening her temperature had shot up to 101.”

She spent July 4 feverish and vomiting. Her family physician told her it was probably just a virus.

When her symptoms worsened and her temperature hit 104.1 on Saturday, she went to the emergency room. Things went downhill fast, with Mohr’s body showing signs of being ravaged by an infection. But tests for standard bacteria and viruses came up negative. With breathing problems and the possibility she might need a liver transplant, she was transferred to the University of Chicago hospital.

Suspecting a possible link to the experimental drug, the doctors in Chicago contacted FDA.

Federal regulations require a company to report any serious complications that are even “possibly” related to an experimental treatment “as soon as possible” and no later than seven days after learning of it. But Targeted Genetics and Trapp had at first classified the problems as not serious, and later classified them as serious but unrelated to the treatment. So no FDA report was made, and the study went on, with other volunteers unaware of the problems.

That reflects a widespread problem in clinical trials, said Adil Shamoo, a professor at the University of Maryland School of Medicine and editor-in-chief of the journal “Accountability in Research” and a member of the advisory committee of BioResearch Compliance Report.

“There are no uniform standards for adverse events reporting,” Shamoo said. “And there is no motivation to report them. . . . No one wants to show their dirty linen.”

Company officials said the drug does show promise by some measures. “We don’t know what the best indication of efficacy is yet,” Barrie Carter, the company's chief scientific officer, told The Post.

Finally, on July 20, a day after Mohr’s emergency transport to Chicago and four days before she died, the company sent a “serious adverse event” report to FDA and suspended the study, conceding that her life-threatening symptoms were “possibly” due to the treatment.

Three weeks after Mohr got the injection that she had hoped would cure her, she was unconscious and beyond hope of recovery. With family and friends gathered around, her life support was removed.

Tests on Jolee Mohr’s tissues may tell the story of what happened, but for now scientists say they are scratching their heads.

One reassuring aspect of tgAAC94’s engineering is that genes required for replication have been removed, so the viruses cannot make more of themselves. But animal studies conducted by the company have shown that the product can escape from the joint space and travel about the body, perhaps catching the attention of the immune system. In general, the immune system mounts much more robust -- sometimes dangerously robust -- responses after a second exposure. In fact, both shots Mohr got were the real thing, the company said.

Further complicating matters, Mohr was on three conventional but potent arthritis drugs, each of which can cause serious side effects.

Years ago, when Targeted Genetics first sought permission to test tgAAC94 in people, federal reviewers approved a single dose in patients who were not taking other drugs but said they would think twice about approving multiple shots or testing in people taking other arthritis medications, The Post reported. Some questioned whether the risk of even a single shot was worth it for a non-life-threatening disease such as arthritis, according to the minutes of meetings at the National Institutes of Health, which used to review, in public, every proposed human gene therapy experiment.

After completing its initial study of single shots, Targeted Genetics sought permission to start giving two -- and to patients taking other drugs. Whatever discussion led up to that approval is hidden from the public because of a federal rule change in 2000 that placed most such follow-on studies under confidential FDA review rather than a public NIH process.

 Conflict of interest

Bill calls for FDA to end all conflicts of interest

Rep. Maurice Hinchey (D-NY) attached language to an agriculture appropriations bill passed by the House that would require FDA to eliminate all conflicts of interest on outside advisory panels whose votes heavily guide the agency’s decision-making, the “Boston Globe” reported Aug. 7.

The funding measure next moves to the Senate, where the FDA conflicts section faces a tough fight; opponents include Sen. Edward Kennedy (D-MA.)

Regardless of the Hinchey proposal's fate, such congressional chatter might trigger FDA to act forcefully on its own, the Globe stated.

Under congressional pressure, the agency said earlier this year that it intends to bar advisers with financial ties to drug and medical device companies that exceed $50,000. Even researchers whose grants or consulting fees amount to less than $50,000 during the previous 12 months would be affected under the draft guidance; they would be allowed to serve as FDA advisers but could not vote on the meeting’s outcome. FDA is still sifting public comments and has not issued a final proposal.

The moves come amid unprecedented attention to the billions of dollars in drug industry funding that flow through academia and the nation’s top hospitals. Because so many leading researchers accept drug and device company funding, FDA has said it has a difficult time eliminating all traces of financial ties among its advisers, the Globe reported. Often it can’t find enough scientists free of conflicts within FDA or other federal health agencies, such as NIH and the CDC. FDA has argued that it must retain the latitude to grant waivers so the nation’s finest scientific talent will be able to serve on advisory panels.

That’s a viewpoint endorsed by Kennedy, who noted that doctors Craig Mello and Phillip Sharp, Nobel-Prize-winning Massachusetts scientists, would face limits on their participation on FDA panels if Senate proponents of the stricter rules were successful.

“Many of the nation’s best scientists wear both hats—working in an academic lab one day and consulting for a start-up biotech firm the next,” Kennedy said in May, rejecting a move to impose an “inflexible” cap on the number of waivers FDA can grant.

Last week, for example, five researchers on the 26-member panel that decided to keep the diabetes drug Avandia on the market had financial ties to GlaxoSmithKline, its manufacturer, or to rival companies.

John Teerlink, M.D., director of the heart-failure clinic at the San Francisco Veterans Affairs Medical Center, reported receiving the highest level of funding— between $10,001 and $50,000 as a reviewer for a drug company that competes with Glaxo and $50,001 to $100,000 in stock held in a health sector mutual fund. Teerlink, permitted to vote by FDA, agreed with the majority that Avandia’s emerging heart attack risks are real, but he also voted to keep the drug on the market.

Curt Furberg, M.D., who also served on the Avandia panel, expects congressional interest will lead FDA to further refine what it considers to be a conflict of interest. Furberg is paid $200 annually to consult for the NIH on a diabetes study that includes Avandia. FDA permitted him to serve as a temporary adviser for the Avandia panel but barred him from voting.

Furberg, a drug safety expert at Wake Forest University School of Medicine, and others have argued that FDA packs panels with clinicians more apt to keep questionable products on the market to help their patients but includes fewer drug safety proponents who argue for restrictions and market withdrawals.

“My assumption is it is going to be tougher to stack the committee with people who have conflicts,” Furberg said. “The first step is to limit the number of people with potential conflicts. The other is to define conflict more explicitly.”

Grassley calls for registry of drug firms paying doctors

Sen. Charles Grassley (R-IA) will propose legislation requiring drug makers to disclose the payments they make to doctors for services like consulting, lectures and attendance at seminars, “The New York Times” reported Aug. 3.

Grassley, the senior Republican on the Senate Finance Committee, cited as an example the case of a prominent child psychiatrist who he said made $180,000 over just two years from the maker of an anti-psychotic drug now widely prescribed for children.

Grassley is one of several lawmakers to propose a federal registry of such payments. Minnesota, Vermont and Maine already have similar registries, and other states are considering them.

The proposals are a response to growing concerns that payments from drug makers can affect doctors’ prescribing habits, increase the cost of health care and, in some cases, endanger patients’ health.

The drug industry opposes such registries, saying they would discourage doctors from receiving needed education. John Bentivoglio, a lawyer in Washington who represents drug makers, said the registries would be a burden for the companies and might be misinterpreted.

“One of the concerns is that these payments are seen as bribes,” Bentivoglio told The Times. “That’s not the case. The vast majority are lawful payments for services.”

In a speech on the Senate floor Aug. 2, Grassley said he had started an investigation into these practices. Noting that most universities require academic researchers to disclose such payments, he said, “I have sent letters to a handful of universities to understand how well such a reporting system actually works.”

These letters have uncovered several problems, Grassley said. First, universities do not verify the information filed by their professors, so “the only person who knows if the reported income is accurate and complete is the doctor who is receiving the money.”

Also, the universities generally keep this information secret from patients, who have no way of knowing whether their doctor is on a drug maker’s payroll, he said.

“So if there is a doctor getting thousands of dollars from a drug company — payments that might be affecting his or her objectivity — the only people outside the pharmaceutical industry who will probably ever know about this are the people at that very university,” he said.

Grassley said that he had asked how much the child psychiatrist, Melissa DelBello, M.D., at the University of Cincinnati, made from AstraZeneca, which manufactures the anti-psychotic Seroquel.

DelBello’s studies of Seroquel in children have helped to fuel the widespread pediatric use of anti-psychotic medicines. Those studies were inconclusive, but she has described them as demonstrating that Seroquel is effective in some children.

Asked in a past newspaper interview how much she was paid by AstraZeneca to help market Seroquel, she said: “Trust me, I don’t make very much.”

Grassley said this week that her disclosure forms at the University of Cincinnati show she received $100,000 from AstraZeneca in 2003 and $80,000 in 2004. DelBello consults for seven other drug makers as well. She did not respond to requests for comment this week, The Times reported.

Richard Puff, a university spokesman, said he did not know how much DelBello made in combined payments from all eight drug makers. Asked if the institution did anything to verify its professors’ financial disclosures, he replied, “We do trust our faculty when they’re making these disclosures.”

Grassley said he would propose that drug makers make public any payments made to doctors who bill the federal Medicare and Medicaid programs, which would include nearly all doctors.

Noting that voters can easily look up the contributions made to elected officials, he asked, “Shouldn’t we hold doctors to similar standards?”

Legislation

House approves prescription drug imports

The House of Representatives passed legislation Aug. 2 effectively permitting the importation of lower-cost prescription drugs from places such as Canada, Australia and Europe, The Associated Press reported.

The move came as lawmakers passed a $91 billion spending measure funding farm subsidies and nutrition programs for the budget year beginning Oct. 1.

The bill, passed by a 237-18 vote, faces a promised veto from President Bush over its price tag, and the administration also opposes the drug importation provision.

The sprawling measure is the final domestic spending bill to pass the House. It contains almost $1 billion more than requested by Bush. But the overall measure is more than $10 billion below comparable costs for the current budget year because it does not contain farm disaster aid and reflects lower crop subsidy costs due to the good farm economy.

The administration “strongly opposes” the drug provision, which would effectively permit individuals, wholesalers and pharmacists to import lower cost U.S.-made and FDA-approved prescription drugs from Canada and other countries.

The White House says there is no system in place to protect consumers from counterfeit or unsafe drugs, but an administration policy statement stops short of an outright veto threat.

“I understand the intention to lower drug prices to the seniors, that is critically important,” said Rep. Mike Rogers, (R-MI). “What we’re doing is throwing open the gates to every (drug) counterfeiter in the world.”

A move supported by drug companies to strike the drug importation provisions from the bill was defeated 283-146.

Supporters of the idea say it would save consumers great sums by allowing them to purchase U.S.-made medications from other countries where they often sell for much lower prices than in the U.S. Under current law, consumers are permitted to buy a 90-day supply in Canada.

Overseas, drugs can cost two-thirds less than they do in the United States, where prices for brand-name drugs are among the highest in the world. In many industrialized countries, prices are lower because they are either controlled or partially controlled by government regulation.

“I would prefer to stand up for my constituents in Missouri as opposed to the pharmaceutical companies keeping competition and low prices out of this country,” said Rep. Jo Ann Emerson (R-MO.)

Similar drug importation language has passed the House in recent years but has been forced out by GOP leaders and the White House during House-Senate negotiations.

CDC to provide investigational drug for severe malaria

The Centers for Disease Control and Prevention (CDC) has received permission from FDA to provide intravenous artesunate for emergency use in the United States for persons with severe malaria.

Artesunate, a derivative from the quing hao or sweet wormwood plant, has been used worldwide for more than 20 years for the treatment of malaria. FDA has not approved artesunate for marketing in this country. CDC's IND application limits the use of artesunate to the emergency treatment of severe malaria, and the drug can be provided only through CDC.

“The introduction of artesunate marks an important improvement in the way we are able to treat those with the most severe cases of malaria,” Paul Arguin, head of the domestic malaria unit at CDC, said in a statement released by the agency. “Intravenous drugs are the most effective way to treat those with severe malaria. Until now, quinidine was the only IV drug that could be used and it was often not readily available in hospitals. Artesunate is considered to be more effective and has fewer side effects than quinidine, and we’re hopeful that its use will cause a decrease in the number of deaths from malaria.”

Although eliminated from the United States in 1951, malaria can still affect U.S. residents who travel or work abroad. Approximately 1,400 cases of malaria are diagnosed in this country each year; approximately 10% of them are cases of severe malaria. The World Health Organization (WHO) has recommended artesunate in preference to quinidine for treatment of severe malaria since 2000.

The Walter Reed Army Institute for Research (WRAIR) within the U.S. Department of Defense collaborated with HHS and CDC on the development of the artesunate protocol as an IND to expedite its availability, and will now be providing a supply of the medication to CDC. Artesunate may be used to treat malaria patients who need IV treatment because of severe disease, who have high levels of malaria parasites in the blood, who are not able to take oral medications, who do not tolerate quinidine, who may have an adverse reaction to quinidine, or in those whom quinidine treatment has proven ineffective.

The CDC Drug Service or one of the CDC Quarantine Stations located around the country will provide the drug to hospitals upon request and on an emergency basis. Physicians who receive the drug will be requested to notify CDC of any adverse event following administration of the drug.

R&D

Pfizer builds Phase III pipeline, slows development of CETP drugs

Pfizer announced Aug. 6 that it is still studying a class of experimental drugs with potential to raise good cholesterol, but which also raised safety concerns. The two compounds remain in Phase I of development and aren’t being advanced for the time being, a spokesman told “The Wall Street Journal.”

The two early-stage drugs are known as inhibitors of cholesteryl ester transfer protein (CETP). Last year, Pfizer halted late-stage development of torcetrapib, also a CETP inhibitor, after a trial showed it was associated with an increased risk of death.

After torcetrapib’s failure, Pfizer had left open the possibility that it would still pursue two backup CETP compounds that were in early-stage development. Pfizer noted these compounds weren’t associated with increased blood pressure, as torcetrapib was.

In an update of its research pipeline, Pfizer said the two backup CETP inhibitors were still in Phase 1 development and haven't been advanced to the next phase.

Pfizer’s head of research, John LaMattina, noted that clinical data released in March showed that torcetrapib had no effect on arterial plaque buildup despite boosting levels of good cholesterol.

Merck and Roche have previously said they were developing their own CETP inhibitors.

Pfizer also said it substantially increased its number of mid-stage drug development programs. Pfizer now has 47 programs in Phase II, the largest in its history and up from the mid-30s as of last December. Pfizer said the increase would help it achieve its goal of tripling its Phase III pipeline by 2009.

Stem cell research/genetics

Within discredited stem cell research, a true scientific first

A team of Boston scientists has re-examined stocks of the purported embryonic stem cells that Korean scientist Hwang Woo Suk said he had derived from adult cells, and arrived at a surprising conclusion: His embryonic stem cells were the product of parthenogenesis, or virgin birth, meaning they were derived from an unfertilized egg.

A team led by Kitai Kim and George Daley of Children’s Hospital Boston reported this conclusion Aug. 3 in the journal “Stem Cell,” according to “The New York Times.”

Embryonic stem cells derived through parthenogenesis cannot develop normally, so they are free of ethical objections. The cells could perhaps help treat degenerative diseases in women capable of supplying eggs, should effective treatments ever be developed.

Other researchers have since developed embryonic stem cells from parthenogenetic eggs, but Hwang’s team would have been the first to do so had its members recognized what they had done. However, Hwang’s claim was discredited after parts of his research were found to have been faked.

“It could have been a seminal finding if they hadn’t had their blinders on,” said Kent Vrana, an expert on parthenogenesis at Pennsylvania State University, told The Times.

John Gearhart, a stem cell expert at Johns Hopkins University who had a ringside view of the Hwang affair as a member of the advisory board for the journal “Science” said parthenogenesis had always been a possibility.

“I’m delighted there was an explanation that didn’t involve fraud,” Gearhart said.

Hwang soared to prominence after asserting in a report in Science in 2004 that he had developed embryonic stem cells from a patient, the first hurdle in the idea of rebuilding patients’ tissues with their own cells.

He said he had removed the nucleus from an unfertilized human egg and inserted a new nucleus from the adult cell of the patient. The egg developed into an embryo, from which his team claimed to have developed embryonic stem cells.

The editors of Science later retracted the article because the Korean committee that investigated Hwang’s work found that the supporting data had been faked.

As to the source of Hwang’s embryonic stem cells, the Korean committee said parthenogenesis was possible. But this could not be proved with the methods then available.

Daley has been studying parthenogenesis in mice with new devices that can analyze DNA at up to 500,000 sites on the genome. Recognizing that parthenogenetic cells have a special and unexpected genetic signature, Daley realized he could resolve the origin of Hwang’s cells.

“It becomes an historic irony that Hwang was the first to produce the parthenogenetic stem cell but didn’t appreciate what he had,” Daley said.

New gene targeting aggressive lung cancer identified

Scientists from the University of North Carolina at Chapel Hill School of Medicine and Harvard Medical School announced that they have discovered a powerful, tumor-suppressing gene, which they call LKB1.

The research, published Aug. 5 in the online edition of the journal “Nature,” found that LKB1 is a mutation in almost one quarter of all lung cancers. And experiments with laboratory mice indicate that this type of lung cancer causes tumors that are more aggressive and more likely to spread throughout the body.

“Defects in this gene appear to result in a much nastier form of lung cancer, a disease that is bad to begin with,” said senior author Norman Sharpless, M.D., assistant professor of medicine and genetics at the UNC School of Medicine, in a university news release.

Identifying the gene can now give physicians a better chance of giving a better prognosis and targeting a more precise therapy for lung cancer patients.

“Based on this study and ones like it, we should be able to sort patients into groups based on exactly what genetic lesion is causing their cancer,” said UNC assistant professor of medicine Neil Hayes, M.D., co-author of the study, in the news release. “Then we can make better treatment decisions depending on which therapy is most likely to target that defect.”

 

International

Pfizer asks Nigerian court to quash report

Pfizer said Aug. 3 that it has asked a court to disallow a Nigerian government report from being considered in lawsuits alleging that a drug experiment led to deaths and disabilities among children over a decade ago.

The company said it filed its petition Thursday at the Federal High Court in the Nigerian capital, Abuja, asking judges to rule that the government's findings were "illegal and inaccurate and should therefore be quashed."

Government lawyers were not immediately available for comment. It was unclear when a ruling could be expected.

Pfizer treated 100 meningitis-infected children with an experimental antibiotic, Trovan, in a 1996 study. Another 100 children, who were control patients, received an approved antibiotic, though families lawyers' have claimed the dose was lower than recommended.

The government has charged that the company conducted the study without the full knowledge of parents or proper regulatory approval - contributing to deaths of some children and illness in others.

Eleven children died - five of those on Trovan and six in the control group, while others suffered physical disabilities and brain damage. Pfizer has insisted its records show none of the deaths was linked to Trovan or substandard treatment, noting that the study showed a better survival rate for the patients on Trovan than those on the standard drug, and that mental damage and other serious disabilities are known aftereffects of meningitis.

The government has filed four separate cases at the federal and local levels, seeking billions of dollars in damages from Pfizer.

Pfizer said in a statement Friday that it had not been allowed to cross-examine witnesses interviewed for the government report, which it said was the basis of all four suits. It also said officials involved in writing the report were biased.

Authorities in Kano state have blamed the Pfizer affair for widespread suspicion of government public health policies, particularly the global effort to vaccinate children against polio.

Islamic leaders in largely Muslim Kano had seized on the Pfizer controversy as evidence of a U.S.-led conspiracy. Rumors that polio vaccines spread AIDS or infertility spurred Kano and another heavily Muslim state, Zamfara, to boycott a polio vaccination campaign four years ago.

Vaccination programs restarted in Nigeria in 2004, after an 11-month boycott. But the delay set back global eradication. The boycott was blamed for causing an outbreak that spread the disease across Africa and into the Middle East.

 

Trial Briefs

Genzyme announced that its second Phase III trial of Mozobil (plerixafor) has successfully met its primary and secondary endpoints, demonstrating positive results in multiple myeloma (MM) similar to those reported in non-Hodgkin's lymphoma. The randomized, double-blind, placebo-controlled trial included 302 patients who were undergoing a hematopoietic stem cell transplant (HSCT) for multiple myeloma at medical centers in the United States, Canada and Europe. It examined the effectiveness of Mozobil in increasing the number of hematopoietic stem cells collected for a transplant, comparing the stem cell yield from patients treated with Mozobil following G- CSF to patients treated with placebo following G-CSF. In the primary efficacy endpoint, 72% of patients treated with Mozobil and G-CSF achieved the target threshold for collection of at least 6 million CD34+cells/kg from the peripheral blood with two days or fewer of apheresis sessions, compared with 34% of patients in the G-CSF/placebo group. This two-fold increase was statistically significant in favor of the Mozobil-treated patients. These results exceed the 20% absolute difference prospectively defined through FDA’s SPA as a successful result. Over half of patients treated with Mozobil and G-CSF reached the target cells in the first day of apheresis. By comparison, it took four days for a similar percentage of the G-CSF/placebo group to reach this threshold. Secondary outcomes were consistent with the primary endpoint, showing a statistically significant result in favor of Mozobil in the number of patients who reached the target threshold of at least 6 million CD34+cells/kg from the peripheral blood with four days of apheresis, and the number of patients who reached at least two million cells collected in four days. The trial also robustly met the primary endpoint specified by the European Agency for the Evaluation of Medicinal Products (EMEA) -- a composite of successful mobilization and engraftment. http://media.prnewswire.com/en/jsp/latest.jsp?resourceid=3528165&access=EH

Iomai announced that its patch-based vaccine for enterotoxigenic E. coli (ETEC) bacteria conferred statistically significant protection from travelers' diarrhea as compared to placebo, particularly for more severe cases, according to interim data from a double-blind Phase II field study. Vaccinated travelers were 75% less likely to suffer moderate or severe diarrhea from any cause and 84% less likely to be afflicted by severe diarrhea. No vaccine-related serious adverse events were reported. In addition to the protective effects, investigators found that the frequency and duration of diarrhea in vaccinated subjects who did contract disease was significantly lower than in their unvaccinated peers. The Trek Phase II field study followed 170 subjects, 111 who received a placebo and 59 who received two doses of Iomai's patch-based vaccine before traveling to Mexico or Guatemala. These efficacy results were particularly notable as the trial was conducted largely to gather information on the logistics of conducting such a study in the field. Iomai's vaccine uses the company's novel transcutaneous immunization (TCI) technology, which allows the vaccine to be delivered to the immune system via a simple patch affixed to the skin. The study met its primary endpoints, which were designed to evaluate the safety of the vaccine and the incidence of ETEC. The secondary objectives included evaluation of vaccine-preventable outcomes, immunogenicity and stool frequency. The study also gathered data on the protective efficacy of the vaccine. Iomai plans to submit the full dataset from the trial for publication as soon as possible. The company intends to launch a Phase III program for the vaccine in 2008. http://media.prnewswire.com/en/jsp/latest.jsp?resourceid=3526663&access=EH

Medicure announced that data from MR PCI (Multicenter Registry of High-Risk Percutaneous Coronary Intervention and Adequate Platelet Inhibition), a head-to-head study comparing the platelet inhibition effects of Aggrastat (tirofiban hydrochloride) and Integrilin (eptifibatide) indicates a higher degree of platelet inhibition with high-dose Aggrastat versus double-bolus Integrilin at 10 minutes and at six to eight hours in patients with acute coronary syndrome undergoing elective high-risk PCI. In addition, the study demonstrated that significantly more patients achieved >95% inhibition of platelet aggregation (IPA) with the high-dose Aggrastat regimen. Aggrastat, in combination with heparin, is indicated for the treatment of acute coronary syndrome, including patients who are to be medically managed and those undergoing percutaneous transluminal coronary angioplasty (PTCA) or atherectomy. In this setting Aggrastat has been shown to decrease the rate of a combined endpoint of death, new myocardial infarction or refractory ischemia/repeat cardiac procedure. http://www.therapeuticsdaily.com/news/article.cfm?contentvalue=462757&contenttype=newsarchive&channelID=26

MicroDose Technologies announced topline results from a glucose clamp study of the QDose inhaled insulin product. MicroDose, through its joint venture with Vectura Group has developed a highly efficient, rapid-acting, insulin inhaler based upon MicroDose’s proprietary electronic inhaler technology and Vectura’s dry powder insulin formulation. The QDose inhaled insulin product offers dose titration capability over a broad range of dose strengths, in a single inhalation. The inhaler also provides active dose feedbacks to the patient in an easy to use, pocket-sized device. The study employed the widely used and validated glucose clamp technique, and results demonstrated that the inhaled insulin formulation was safe and effective. Peak levels of insulin activity were achieved more quickly following the inhaled insulin than those from the subcutaneous insulin injection. Relative bioavailability of inhaled insulin was approximately 18% during the three-hour period following dosing. The study was a randomized, crossover, open-label glucose clamp study, designed to confirm the high relative bioavailability of the QDose insulin formulation previously observed, and to demonstrate the product's dose titration capability. The study was conducted in the United States at Profil Institute for Clinical Research in San Diego, with 14 healthy male volunteers, using a glucose clamp technique. http://media.prnewswire.com/en/jsp/latest.jsp?resourceid=3529948&access=EH

Pharmion announced topline results from the multi-institutional, international, randomized, Phase III controlled trial of Vidaza (azacitidine for injection) versus conventional care regimens (CCR) in the treatment of patients with higher-risk myelodysplastic syndromes (MDS). In the primary endpoint analysis, Vidaza treatment was associated with a median survival of 24.4 months versus 15 months for those receiving CCR treatment, an improvement of 9.4 months with a stratified log-rank p-value of 0.0001. The hazard ratio describing this treatment effect was 0.58 (95% confidence interval of 0.43 to 0.77). Two-year survival rates were 50.8% versus 26.2% for patients receiving Vidaza versus CCR. Median number of treatment cycles was nine for Vidaza. The survival benefits of Vidaza were consistent regardless of the CCR treatment option (best supportive care (BSC) alone, low-dose cytarabine plus BSC or standard chemotherapy plus BSC) utilized in the control arm. http://media.prnewswire.com/en/jsp/latest.jsp?resourceid=3528070&access=EH

Q-Med AB reported that a study shows that Deflux (non-animal stabilized hyaluronic acid/dextranomer gel) for the treatment of vesicoureteral reflux (VUR) in children reduced the incidence of recurrent urinary tract infections (UTIs) in children with VUR by 62%. Deflux also eliminated the need for prophylactic antibiotics in 87% of patients. VUR, a malformation of the ureter that causes a backflow of urine from the bladder toward the kidneys, is the most common abnormality of the urinary tract in children. In this prospective study, the charts of 100 children aged one to 17 years with VUR from Baystate Children's Hospital, Tufts University School of Medicine in Springfield, MA were reviewed. All patients were kept on prophylactic antibiotics for three months after Deflux injection. After treatment with Deflux, 13% had recurrent UTIs compared to 75% before Deflux treatment, with a five-fold reduction in the incidence of UTIs per year post-treatment. The overall success rate by ureter of Deflux treatment in resolving VUR was 77.4% after the first injection and 83.9% after a second injection. There were no major intraoperative or post-operative complications. http://media.prnewswire.com/en/jsp/latest.jsp?resourceid=3530966&access=EH

Trial Updates

Antisoma announced that it has started a randomized phase II trial of AS1411 in AML (acute myeloid leukemia). Around 70 patients will be recruited at major cancer centers in the U.S. to evaluate the addition of AS1411 to the current standard therapy, cytarabine (Ara-C), in patients with relapsed or refractory AML. Efficacy and safety will be compared to see whether patients receiving a cytarabine-AS1411 combination do better than those receiving cytarabine alone and whether the two doses of AS1411 have different effects. Initial results are expected in 2008. AS1411 was the first anti-cancer aptamer to start clinical trials and becomes the first to progress to Phase II. Pre-clinical data suggest that AS1411 has potential against various blood cancers and solid tumors. AML was selected as the lead blood-cancer indication because cancer cells from AML patients and AML cell lines show particularly high sensitivity to AS1411. There is also evidence for a synergistic effect when AS1411 is combined with cytarabine. http://www.therapeuticsdaily.com/news/article.cfm?contentvalue=1450955&contenttype=sentryarticle&channelID=28

Array BioPharma filed an IND application for ARRY-380 with FDA and is now able to proceed with a Phase  I clinical trial in cancer patients. ARRY-380, a selective, orally-active ErbB-2 inhibitor, has shown good efficacy in pre-clinical models of human breast cancer resulting in significant anti-tumor activity. The company believes the oral drug may broadly benefit HER2-positive cancer patients, including those who are Herceptin-resistant. Array plans to commence the Phase  I clinical trial this fall in the United States and Canada. The open-label, multiple dose study is designed to evaluate safety, tolerability and pharmacokinetics of ARRY-380 following daily oral administration to patients with advanced cancer. ARRY-380, a selective, orally-active inhibitor of ErbB-2, a receptor kinase target that has been found to be over-expressed in breast and other cancers. Herceptin, the intravenously-dosed protein therapeutic currently on the market, modulates ErbB-2. The company belies the advantages of ARRY-380 include patient preference for an orally-active drug as well as improved efficacy versus or in combination with standard of care in pre-clinical models of human breast cancer. http://www.therapeuticsdaily.com/news/article.cfm?contentvalue=464838&contenttype=newsarchive&channelID=28

BioChem Solutions announced it has now committed to proceeding with the Phase III trials for Arthromir and Alphamir drugs that have been developed and derived from trioxolane. This research is being conducted under FDA protocol guidelines at the Kenya Medical Institute (KEMRI) and is piggy-backed onto the favorable results seen in the Phase II trials conducted in 2004. In these trials, two groups of 200 people will be included within the test and control groups with the testing to be completed over a three-month period and then a subsequent two-month evaluation period. Testing will be done for the treatment of acute respiratory infections, rheumatoid arthritis and HIV. http://www.therapeuticsdaily.com/news/article.cfm?contentvalue=462145&contenttype=newsarchive&channelID=29

Bristol-Myers Squibb announced that FDA has accepted for filing and review, the sBLA for Orencia (abatacept) for the treatment of pediatric patients with juvenile idiopathic arthritis (JIA) who have had an inadequate response to one or more disease-modifying anti-rheumatic drugs (DMARDs) such as methotrexate (MTX) or tumor necrosis factor (TNF) antagonists. This sBLA is based on data from a double-blind, randomized trial in which all participants (6-17 years old) received Orencia and both clinical response and safety were assessed; a six-month randomized double-blind withdrawal phase in which responders received either Orencia or placebo and time to disease flare and safety were assessed (Period B); and an open-label phase in which all participants received Orencia order to assess long-term efficacy and safety (Period C). Orencia, which was discovered and developed by Bristol-Myers Squibb, is currently approved for use in adults with moderate to severe rheumatoid arthritis (RA) who have had an inadequate response to one or more DMARDs such as MTX or TNF antagonists. Orencia is a selective modulator of a co-stimulatory signal required for full T-cell activation. http://media.prnewswire.com/en/jsp/latest.jsp?resourceid=3531126&access=EH

Genaera reported that development partner MedImmune has initiated a multi-dose, Phase IIa clinical trial with its monoclonal antibody (MAb) targeting interleukin-9 (IL-9) in adults with mild, persistent asthma. The placebo-controlled, dose-escalation study is designed to evaluate the safety and tolerability of multiple doses of the antibody. This trial is the second Phase  IIa study currently underway with the MAb, known as MEDI-528. Genaera and MedImmune entered into a collaborative licensing agreement for this program in 2001. Two previous Phase I single-dose, dose-escalation studies have been conducted to evaluate the safety, tolerability and pharmacokinetics of the anti-IL-9 MAb in healthy volunteers. The antibody was well tolerated in both studies. MedImmune is also conducting an ongoing Phase IIa study, initiated in late 2006, to evaluate the efficacy of a single intravenous dose of MEDI-528 and its effect on disease mechanisms in adults with atopic asthma. Plans to initiate a third Phase IIa study to evaluate the ability of MEDI-528 to inhibit the biological activity of IL-9 in the bronchoalveolar lavage fluid of adult patients with atopic asthma are underway. http://media.prnewswire.com/en/jsp/latest.jsp?resourceid=3527131&access=EH

GlaxoSmithKline marked the start of the first pre-pandemic vaccine trials involving its proprietary adjuvanted H5N1 vaccine in North America. These U.S. studies are supported by a contract from BARDA/ASPR/HHS awarded in January for the advanced development of antigen-sparing pandemic influenza vaccines towards U.S. licensure with a commitment to U.S. production of 150 million doses of pandemic vaccine within six months of a pandemic onset. Data from earlier European studies, using a pre-pandemic vaccine produced at GSK's Dresden, Germany facility, showed that the influenza candidate vaccine may be able to induce immune responses that might protect against different strains of H5N1. GSK's first North American pre-pandemic vaccine trial will be a Phase I/II study that evaluates its H5N1 antigen alone and in combination with one of its proprietary Adjuvant Systems, in 675 subjects. This Phase I/II study is expected to lead into a larger, multi-center, Phase III trial - one of the largest in North America - which is expected to enroll approximately 4,400 subjects later in 2007. This Phase I/II study, which will be conducted in seven states in the United States and two provinces in Canada, is an observer-blind, randomized, active-controlled trial that will evaluate the safety and immunogenicity of two consecutive doses of H5N1 pre-pandemic vaccine. The vaccine containing H5N1 antigen alone will be evaluated against a vaccine containing H5N1 antigen in combination with the Adjuvant System, in 675 adult volunteers aged between 18 and 64 years. Results from this study will be available in early 2008.

Hana Biosciences announced the initiation of a multi-center, multi-national Phase  II clinical trial of Marqibo (vincristine sulfate injection, OPTISOME) in adult patients with relapsed acute lymphoblastic leukemia (ALL), also known as the rALLy study. Earlier this year, Marqibo was granted Orphan Drug Designation by FDA for the treatment of adult ALL. The primary objective of the rALLy study is to assess the efficacy and tolerability of weekly doses of Marqibo as a single agent without dose capping, measured by complete response (CR) rate or complete response without full platelet recovery (CRp). Secondary objectives include evaluation of safety, duration of CR/CRp and survival. The patient population is defined as Philadelphia chromosome-negative adult patients in second relapse, or those patients who relapsed following two lines of anti-leukemia chemotherapy, including those who have previously undergone stem cell transplantation. In this trial Hana expects to enroll up to 56 patients. The company also plans to initiate a Phase  III randomized, multi-center trial comparing Marqibo to vincristine in the induction, consolidation and maintenance phases of treatment in elderly patients with newly diagnosed ALL. http://www.therapeuticsdaily.com/news/article.cfm?contentvalue=464815&contenttype=newsarchive&channelID=28

ImmunoCellular Therapeutics announced that the first three patients have been enrolled in the recently commenced Phase I clinical trial of its lead brain tumor vaccine product candidate. The vaccine trial is being conducted at the Johnny L. Cochran, Jr. Brain Tumor Center at Cedars-Sinai Medical Center in Los Angeles. The IMUC vaccine is a dendritic cell-based vaccine that could potentially bolster the body's natural tendency through its immune system to defend itself against malignant brain tumors. Dendritic cells play a central role in the body's immune response. The IMUC vaccine is based on a proprietary technology that has been exclusively licensed to the company by Cedars-Sinai. http://www.therapeuticsdaily.com/news/article.cfm?contentvalue=464776&contenttype=newsarchive&channelID=28

Kosan Biosciences announced that Pfizer has initiated a Phase  I clinical trial of motilin receptor agonist PF-04548043, formerly KOS-2187, a selective and potent motilin receptor agonist being developed for the treatment of gastroesophageal reflux disease (GERD) and potentially other gastrointestinal (GI) disorders. The Phase  I clinical trial is designed to test the safety, tolerability and pharmacokinetics of PF-04548043 in healthy subjects. In December 2006, Kosan and Pfizer established a worldwide license agreement for Kosan's motilin agonist program, including KOS-2187 and related compounds. http://media.prnewswire.com/en/jsp/latest.jsp?resourceid=3529767&access=EH

Kosan Biosciences announced that the TIME-2 trial is open and enrolling patients. This marks the opening of Kosan's Tanespimycin in Myeloma Evaluation or TIME registration program for its lead Hsp90 inhibitor, tanespimycin (KOS-953). The TIME program includes two clinical trials. TIME-1 is a pivotal Phase  III trial to be conducted in a first-relapse patient population. TIME-2, which is designed to be supportive of the TIME-1 trial, is a Phase  II/III trial in patients with relapsed-refractory disease. TIME-2 also has the potential to support registration in a relapsed-refractory setting. The TIME program will use Kosan's new, proprietary injectable suspension formulation of tanespimycin. Tanespimycin is the first Hsp90 inhibitor to enter a registration program. A successful outcome in the TIME-2 trial, together with data from our TIME-1 trial, could potentially support an accelerated registration strategy for tanespimycin. The TIME clinical program will utilize Kosan's improved, proprietary injectable suspension formulation of tanespimycin injectable suspension. The formulation is designed to provide improved patient safety due to the elimination of Cremophor and the associated need for steroid premedication to prevent hypersensitivity reactions. Tanespimycin injectable suspension also has a potentially enhanced intellectual property position and permits easier drug preparation and administration compared to the prior formulation. The TIME-2 clinical trial is being conducted at clinical sites primarily in the US and in Europe and is anticipated to enroll approximately 130 patients. The primary endpoint of the trial is the dose response based on objective response rate after four cycles of treatment. Secondary endpoints include a comparison of response rate between the dose groups, progression-free survival, time to treatment failure and overall survival. http://media.prnewswire.com/en/jsp/latest.jsp?resourceid=3527879&access=EH

MacroGenics announced that its Protege trial is actively enrolling adults and children ages 8 to 35 with recent-onset Type 1 diabetes. The global Phase  II/III clinical trial will evaluate the safety and efficacy of three teplizumab dosing regimens administered at the start of the study and again at six months in individuals who are up to 12 weeks from their diagnosis of Type 1 diabetes. Specifically, the Protege study will assess the ability of teplizumab to inhibit the autoimmune attack that destroys insulin-producing pancreatic beta cells in individuals with Type 1 diabetes. If teplizumab is effective and has the ability to preserve or protect beta cells of the pancreas, patients may require less injected insulin and their blood glucose levels may be easier to control. Other research has shown that greater control of blood glucose levels can lead to better long-term health outcomes for patients with Type 1 diabetes. http://media.prnewswire.com/en/jsp/latest.jsp?resourceid=3527927&access=EH

Peregrine Pharmaceuticals announced that the first patient has been administered Cotara in a new clinical trial designed to evaluate the safety and efficacy of this novel tumor necrosis therapy being developed for the treatment of glioblastoma multiforme (GBM), a deadly form of brain cancer. This multi-center open label Phase II safety and efficacy study is designed to enroll up to 40 glioblastoma patients who have experienced a first relapse. The study's primary objective is to confirm the maximum tolerated dose of Cotara in these GBM patients. Secondary objectives include estimates of overall patient survival, progression-free survival and the proportion of patients alive at six months. Patients in the trial are receiving a single infusion of Cotara by convection-enhanced delivery (CED), an NIH-developed technique that delivers the agent to the tumor with great precision, achieving up to a 10,000-fold greater concentration in local therapy exposure than conventional intravenous drug administration, while minimizing unwanted exposure to healthy tissue. This delivery method is expected to further enhance the tumor-killing potential of Cotara, an experimental treatment for brain cancer that links a radioactive substance designed for medical uses--a radioactive isotope--to a targeted monoclonal antibody. This monoclonal antibody is designed to bind to a type of DNA that is exposed only on dead and dying cells. http://media.prnewswire.com/en/jsp/latest.jsp?resourceid=3527997&access=EH

POZEN and GlaxoSmithKline announced that FDA has issued a second approvable letter for Trexima (sumatriptan/naproxen sodium). In January, POZEN and GSK responded to FDA's first approvable letter, submitting additional safety data from clinical trials, data from GSK's database and additional in vitro preclinical data. In the second approvable letter, no additional information regarding the cardiovascular safety of Trexima was requested. The companies agreed to conduct a prospective study after approval to evaluate the effects on blood pressure during chronic, intermittent treatment. FDA has requested that POZEN further address the agency's concern, prior to approval, about the potential implications from one pre-clinical in vitro chromosomal aberration study in which genotoxicity was seen for the combination of naproxen sodium and sumatriptan, but not with either component alone. None of the other three standard genotoxicity studies demonstrated any genotoxicity for the combination of naproxen sodium and sumatriptan. The companies intend to request a meeting with FDA as quickly as possible to discuss the necessary steps to address the agency's concerns. FDA had previously determined that Trexima is effective as an acute treatment for migraine headaches. POZEN and GSK will continue to work with FDA on revisions to the proposed package insert and the proposed trade name. http://media.prnewswire.com/en/jsp/latest.jsp?resourceid=3528176&access=EH

TorreyPines Therapeutics announced that it has completed enrollment in its Phase IIb clinical trial of tezampanel for the treatment of acute migraine headache. Tezampanel is an AMPA/kainate (AK) receptor antagonist that offers a non-opioid, non-vascular and non-serotonergic approach to the management of pain and represents a potentially new and promising alternative to current migraine treatments. The clinical trial is a double-blind, placebo-controlled, multi-center trial that reached its targeted enrollment of 300 patients suffering a single migraine attack, with or without aura. The purpose of the trial is to identify a dose or a range of doses that could be used in a Phase III development program for tezampanel in acute migraine. The primary efficacy endpoint for the trial is headache pain relief at two hours post-dose. Secondary efficacy endpoints include pain-free status at two hours, sustained pain relief and sustained pain-free at 24 hours, and headache recurrence and relapse. Additional measures include assessments of functional disability and patient satisfaction, relief of migraine-associated symptoms such as nausea, vomiting, photophobia (sensitivity to light) and phonophobia (sensitivity to sound), as well as various assessments that characterize speed of treatment onset. Safety, tolerability and plasma pharmacokinetic data will also be evaluated. http://media.prnewswire.com/en/jsp/latest.jsp?resourceid=3529965&access=EH

Wyeth announced that FDA’s demand for further testing of Pristiq, a non-hormonal drug for menopause symptoms, should not delay approval of the same drug as a depression treatment. In a conference call to address concerns triggered by FDA’s decision to require a new study of the drug, officials at Wyeth said they will work closely with FDA to speed the drug's approval as the first non-hormonal treatment for menopause symptoms. FDA  wants more data on Pristiq's effects on the heart and liver, because a very small number of women in studies of the drug for menopause symptoms had serious heart or liver complications. In one of Wyeth's four studies in post-menopausal women, two women in the group taking Pristiq had heart attacks and three needed procedures to repair clogged arteries, compared with none in the group taking dummy pills. In that study, however, there were eight times as many women taking Pristiq as taking placebo. Eight additional factors were listed in Pristiq's defense, including that the five women with heart complications had long-standing heart disease. Still, FDA requested that Wyeth conduct a randomized, placebo-controlled clinical trial of one year or longer. FDA officials have reassured the company the additional safety data required to get approval as a menopause symptom treatment will not hold up approval of Pristiq as a depression treatment.

YM BioSciences announced that it has enrolled the first five patients within the 50-patient initial cohort of its Phase II trial with nimotuzumab in combination with irinotecan for the treatment of patients with colorectal cancer who have previously failed irinotecan-containing regimens. Recruitment of the first cohort is expected to be completed within approximately eight months, following which data on the primary endpoints, response rate and safety, will be reported. The single-arm trial will enroll approximately 100 patients in Canada in two 50-patient cohorts consecutively, with the first cohort receiving irinotecan on one of the conventional dosing schedules with weekly dosing of nimotuzumab and the second cohort receiving irinotecan on one of the conventional dosing schedules with nimotuzumab every two weeks. The first patient was enrolled into the study at the Southlake Regional Health Center in Ontario. Fourteen sites across Canada are expected to participate in the trial, of which two sites are currently open. http://www.therapeuticsdaily.com/news/article.cfm?contentvalue=1449213&contenttype=sentryarticle&channelID=28

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Upcoming ExpertBriefing - August 21, 2:00 - 3:00 pm (EDT)

Effective Responses to FDA Enforcement-The Legal and Regulatory Perspective

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FDA emphasizes a risk-based approach to inspections, but what do you do when an inspector walks into your facility and asks for pricing data, personnel data, or asks your employees to sign affidavits or initial observations on 483s?

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 About the Presenter

Alan G. Minsk, J.D., is a Partner and Chair of the Food & Drug Practice Team of Arnall Golden Gregory LLP in Atlanta. Mr. Minsk advises pharmaceutical, medical device, and food companies on all legal and regulatory matters relating to the U.S. Food and Drug Administration, the U.S. Department of Agriculture, the Federal Trade Commission, the Drug Enforcement Administration, the Consumer Product Safety Commission, and the Alcohol and Tobacco Tax and Trade Bureau. He counsels, speaks and writes on a wide variety of FDA-related issues, including regulatory strategy and lifecycle management, FDA enforcement, market exclusivity, FDA inspections, corporate compliance, promotion and advertising, product liability, imports and exports, and clinical trial issues. Mr. Minsk also conducts in-house training on a wide variety of FDA and fraud and abuse-related topics.

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Oncology Clinical Trials Summit, September 17-18. The Summit focuses on the latest strategies and new technology platforms available in order to address a new and growing problem in Oncology Clinical Trials. The challenge lies in efficiently managing issues associated with underpowered trials, altering therapeutic treatments within the course of a single trial, safety issues with specific emphasis in Cardiac Safety and applying dynamism to the context of an entire development portfolio. For more information and to register please visit www.cbinet.com/clinicaloncology, mention your special promo code of CYE254 to save $100 off of the registration price. 

Regulatory Affairs Professionals Society (RAPS) 2007 Annual Conference & Exhibition, September 23–26. Hynes Convention Center, Boston. Gain insights and perspectives that you’ll find nowhere else about the latest trends in regulatory affairs, across product lines and throughout the product lifecycle. Get proven business strategies and tactics that you can apply directly to your job no matter what your level, and learn about the newest, most innovative products you will want to use right away. Register today for RAPS 2007 Annual Conference & Exhibition. Hotel Reservation Cutoff: Aug. 22 Learning Levels: I, II, III, IV  RAC points: 12 Regulatory Affairs Professionals Society; 5635 Fishers Lane, Suite 550, Rockville, MD 20852; Main Phone: (301) 770-2920; Fax: (301)770-2924; RAPS Solutions Center: (301) 770-2920, ext. 200 Email: raps@raps.org; website: www.raps.org

Clinical Trial Agreements & Budgets Conference West, September 30 - October 3, 2007. San Diego, CA. This year’s West Coast conference features three tracks, over 50 speakers and five post-conference workshops.  Over 30 sessions will cover all of the ins-and-outs of negotiating and budgeting clinical trial agreements, whether your involvement is cross-border or purely domestic. Due to space limitations, this year's conference in San Diego is limited to only approximately 250. To Register NOW - Click here: Yes  To Learn more about the conference, review the agenda, check out our executive speaking faculty -- and more -- visit out website at: www.iibig.com/P0706

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