BioResearch Compliance Report

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

Online Update Page, November 8, 2006


Legislation

Return of Dingell-Waxman-Kennedy FDA oversight expected with Democratic control of Congress; drug safety legislation to advance, Von Eschenbach confirmation seen soon

By Ken Reid, Editor

Until the Republicans took control of the House and Senate in 1994, the two most-feared investigators of FDA issues, Rep. John Dingell (D-MI) and Henry Waxman (D-CA) were in charge of key committees in the House, and their Senate counterpart, Edward Kennedy (D-MA), ruled over the Health and Human Resources Committtee.

As Chairman of the House Energy & Commerce Committee, and its Oversight and Investigations Subcommittee, Dingell was responsible for unearthing the generic drugs payoff scandal at FDA in 1988-89, preparing a blistering report criticizing the agency’s regulation of medical devices in 1993 and assorted investigations into seafood safety, pacemakers, anesthesia machines and of course, drug pricing.

Waxman also investigated FDA at length as chairman of the Energy & Commerce Committee’s Health and Environment Subcommittee. He is responsible for generic drugs legislation in 1984 and the Safe Medical Devices Act of 1990, and also investigated the drug and device industries.

Now, with the Democratic takeover of the House and Senate in the Nov. 7 elections, Dingell is poised to again chair the Energy & Commerce Committee, and Waxman the Government Reform Committee, which also has substantial power in overseeing federal agencies, including FDA. Waxman is also second to Dingell on the Commerce Committee in terms of seniority, and he could chair the Oversight & Investigations Subcommittee, according to an industry source. 

Late tonight (Nov. 8), the Senate went to Democratic control, thus assuring that Kennedy will take the reigns of the Health, Education, Labor and Pensions (HELP) Committee, the successor of the Health and Human Resources Committee.

For the three senior Democrats, FDA is ripe for investigation. Since 2001, when President Bush came into office and the GOP controlled both houses, oversight of the agency has been lax.  The prospects for getting legislation through Congress to reform drug safety and clinical trials oversight have been poor.  Virtually the only oversight of FDA has come from Sen. Charles Grassley (R-IA), regarding drug safety, but he chairs the Finance Committee, which has no say over the Food, Drug & Cosmetic Act or Public Health Service Act. 

Now, the Enzi-Kennedy drug safety bill in the Senate —The Enhancing Drug Safety and Innovation Act of 2006—has new meaning, and oversight of FDA could happen quite quickly.  That bill was introduced in August: See http://www.fdainfo.com/bicoonlinepages/bicoonline080706.htm.

According to Reuters, there is discussion of making changes in the Medicare Rx drug program as part of budget legislation or the renewal of user fees paid to FDA, which is forthcoming. There also will be pressure to allow greater importation of prescription drugs from Canada.

The user fee bill poses the biggest risk for drug makers because it could give Democrats an opportunity to pass tougher post-approval regulation of medicines, importation of cheaper drugs and possibly a limit on consumer-directed advertising, one analyst told Reuters.

Key Democrats also have promised aggressive congressional oversight of drug pricing and other issues.

“You have to ask what [the Democrats] don't like. They don't like Big Pharma. They're going to have a big target on their backs,” Patton Boggs lobbyist John Jonas said.

But WBB Securities analyst Steve Brozak, who made an unsuccessful bid for Congress as a Democrat in 2004, said he did not believe drug makers would become Democrats' favorite whipping boys if they regain power. Instead, he sees the hammer coming down on the FDA and other agencies. “It doesn't do (Democrats) any good to criticize an industry they've got to turn to find the new drugs to deal with the aging baby boomers,” Brozak said.

Whether the Senate is taken over by the Democrats still remains in doubt, as races in Virginia and Montana are so close that recounts are possible.  One industry source, however, expected that the GOP-controlled Senate will confirm Andrew von Eschenbach as commissioner of FDA during the lame duck session, which will begin mid-November.

According to an AP story, “the long-term outlook for companies in the biotechnology and homeland security businesses may benefit, analysts said, from anticipated Democratic efforts to promote stem-cell research and inspect more cargo containers at ports. But the heightened scrutiny of other sectors, ranging from drugs to defense to energy, could cast a shadow that darkens their prospects on Wall Street.”

“The drug industry is on the top of the list of industries that would be uncomfortable if Democrats are successful in the elections,” Ira Loss, an analyst at Washington Analysis, told AP. That’s because House Speaker-presumptive Nancy Pelosi (D-CA) has promised legislation that would allow the government to negotiate directly with drug companies to purchase medicines for Medicare. The drug industry equates the concept to price controls.

Ahead of the voting, drug makers are giving more campaign cash to Republicans. The pharmaceutical and health products industries have contributed more than $9 million to Republican congressional candidates and $4 million to Democrats, according to the nonpartisan Center for Responsive Politics.

Generally speaking, Democrats have said they will differ from Republicans by being tougher watchdogs of corporate wrongdoing and government spending and bigger defenders of consumers and labor unions, according to the AP story.  Dingell, the oldest serving member of the House, has a reputation for being particularly gruff and tough with witnesses.

Dingell told the Detroit News on Nov. 3 that he will use his regained authority on the wide-ranging committee to press for more Medicaid assistance to states, allow the federal government to buy drugs in volume to get discounts for Medicare Part D and push for universal health care. FDA oversight was not listed.

According to the Capitol Hill-oriented newspaper “Roll Call,” leadership of the House will fall to Democrats, with Pelosi becoming the first female House Speaker.  House Minority Whip Steny Hoyer (MD) issued a statement confirming that he will make a bid for Majority Leader.  Like Dingell, Hoyer comes from a state with a drug-device industry presence, but their districts do not have much pharmaceutical, device or biotech employment.

 

“As part of the leadership team that helped regain the House Majority, I would like to continue to serve House Democrats as their Majority Leader,” Hoyer said. “Over the past several months, I have talked with almost every one of my House colleagues and Members-elect, and am grateful for the depth of support I have received.”

 

House Democratic Caucus Chairman James Clyburn (SC) also issued a letter to fellow Democrats on Wednesday confirming his intentions to seek the Majority Whip’s office in the next Congress.  “The Majority Whip is the third-ranking elected leadership position. This will be consistent with my rank as Chairman of the Democratic Caucus, our current third-ranking position,” wrote Clyburn, who cited his leadership experience, including a former Congressional Black Caucus chairmanship and three years as the Caucus vice chairman.

 

While no other contenders for the Whip’s office had announced Wednesday morning, it is possible that House Democratic Congressional Campaign Committee Chairman Rahm Emanuel (D-IL), who has said he will not serve a second term in his current post, could make a bid for the office, although a spokeswoman declined to confirm his interest.  Chief Deputy Minority Whip Diana DeGette (D-CO) is expected to make a bid for the office if Emanuel does not enter the race.  DeGette was co-sponsor of bills in prior years to boost federal rules regarding human subject protections.

 

The Caucus is scheduled to hold its leadership elections Nov. 16, Roll Call reported. 

 

Although more oversight can be expected, it may take time, too.  Many of the investigators and staff on the Dingell committees were cut back when the GOP took control of Congress.  So, a lot of new hires would have to be in place first before the Dingell-Waxman-Kennedy triumvirate gets revved up again.

 

PhRMA defends import bans, Medicare prescription drug program; AdvaMed sees benefits

Despite the prognosis of more oversight and efforts to reign in drug prices and restrictions on prescription drug imports from Canada, the Pharmaceutical Research & Manufacturers of America was upbeat in its official statement regarding the Democratic takeover of the House in the Nov. 7 elections.

“We look forward to working with all members of the new Congress to solve the difficult and challenging health care problems that confront America. As always, we will work with lawmakers from both political parties as we seek to increase patient access to safe and affordable medicines,” said PhRmA President Billy Tauzin, who once served with John Dingell on the Commerce Committee as both a Republican and Democrat before chairing the panel.

But PhRMA also was quick to criticize any efforts to weaken the Medicare prescription drug program, or to relax rules on importing drugs from Canada.  PhRMA Senior VP Ken Johnson stated: “The FDA has the world's best drug safety record. It is widely recognized as the ‘gold standard’.  But importation schemes undermine the U.S. government’s ability to assure us that our drug supply is safe and secure, and can expose Americans to counterfeit drugs and undermine the very system which protects us.”

Regarding drug pricing and the Medicare prescription drug benefit, Johnson said, “Critics infer that there are no negotiations in how prices for medicines are set. That’s simply not true. The negotiations are occurring – as they should be – between prescription drug plans, several of which already purchase medicines on behalf of tens of million of Americans, and pharmaceutical companies. That’s the marketplace in action and that’s how America’s seniors will see true savings without compromising the search for future cures.”    

He added:  “The non-interference clause of the Medicare Act protects against the federal government limiting patients’ access to medicines they need. These protections do not compromise affordability.  Even the Congressional Budget Office has said that government interference ‘would have a negligible effect on federal spending’ and that the government probably could not negotiate lower costs than the powerful private sector purchasers already negotiating for lower costs.” 

 

AdvaMed spokeswoman Barbara Ware said in an email that Dingell “was behind the first iteration of MDUFMA and is expected to be cooperative when it comes up for renewal in 2007.”  She was referring to the medical device user fee law, passed in 2002.  And, she noted: “Dingell also has first-hand experience with devices as he has had stents implanted and got a hip replaced.”

 

Ethics

 

ORI asks for comments on research misconduct policy

 

The Office of Research Integrity (ORI) is inviting public comments on its “Model Policy for Responding to Allegations of Research Misconduct.” The policy has been revised to comply with the Public Health Service Policies on Research Misconduct (42 C.F.R. Part 93). Under that policy, research misconduct is defined as:

  • Fabrication—making up data or results and recording or reporting them;
  • Falsification—manipulating research materials, equipment or processes, or changing or omitting data or results such that the research is not accurately represented in the research record; and/or
  • Plagiarism—the appropriation of another person's ideas, processes, results or words without giving appropriate credit.

The policy specifically states, “Research misconduct does not include honest error or differences of opinion.”

ORI’s Model Policy “… was designed primarily for use by institutions that are developing or refining their policies for handling scientific misconduct cases where ORI has jurisdiction.” It is, the agency noted, “non-binding and…has been developed to provide suggestions to institutions” to ensure that their own research misconduct policies are consistent with 42 CFR Part 93.

Further, the policy states that “institutions may adopt additional standards of conduct that go beyond the PHS standards in 42 CFR Part 93. These additional standards may be included in the same policy document as the PHS standards, but if an institution chooses that option, it should make certain that the two sets of standards and actions under them are easily distinguishable. These additional institutional standards will apply only to the internal decisions at the institution.”

The Model Policy can be read in full at http://www.ori.dhhs.gov/policies/model_policy.shtml. Comments should be sent to Brenda.Harrington@hhs.gov by Dec. 29.

Stem cell research

Proven stem cell cures being thwarted by politics, says advocate for the blind

RP International, a Los Angeles-based organization dedicated to raising funds for research into the causes of and treatments for blindness, will establish a new and separate fund-raising campaign to aid development of adult stem cell treatments for blindness and other disorders, its founder and president announced.

Helen J. Harris said in a release issued by the company that proven cures for blindness using adult stem cells are already available but are being stymied by politics. Although the main political controversy revolves around the use of embryonic stem cells, politics has infected the entire scientific field and has stalled adult stem cell applications as well, she stated.

Acrimonious political campaigns have spread misunderstanding and discouraged funding of all stem cell research in the United States, Harris said. She pointed to an adult stem cell transplant program at a Louisiana State University hospital that was quietly discontinued in the midst of public political rancor, even though it did not involve embryonic cells and had already led to a successful degenerative blindness cure back in 1984. Harris had been personally involved with the project.

Harris and two of her sons are blind due to retinitis pigmentosa. Her organization's 2006 Vision Awards took special note of adult stem cell research by honoring a patient who was able to regain sight thanks to the LSU technique after more than 20 years of blindness.

The chilling effect on stem cell research has not been limited to the LSU program, Harris said, but is a factor holding back research all around, including money that could go to adult stem cell applications. She cited the example of California, where billions of dollars for stem cell research approved by the voters in a 2004 ballot initiative are still being held back by two major lawsuits against the state. 

Clinical Trials

Links to depression, anxiety may delay U.S. introduction of anti-obesity drug

Sanofi-Aventis may face delays in introducing its anti-obesity drug Acomplia in the United States, the company announced, according to a report in the Oct. 31 “International Herald Tribune.”

Sanofi executive Hanspeter Spek told the newspaper that Sanofi submitted new information to FDA, but he could not offer a timeline for approval. FDA has not required more clinical trials, but some analysts have speculated that U.S. approval may be delayed because of data gathered in clinical trials that links Acomplia with anxiety and depression.

Sanofi, the world's third-largest drug company by sales after Pfizer and GlaxoSmithKline, said in February that U.S. approval for Acomplia could come by the end of 2006. Now, the more likely date for release of Acomplia in the United States is mid-2007.

Acomplia works by reducing the patient's urge to overeat and by adjusting the body's metabolism of fats and sugars, according to Sanofi. The drug helps to reduce body weight as well as levels of blood sugars and bad fats, while boosting good cholesterol.

Marketing of Acomplia was first approved by EMEA in June. Since then, Sanofi has introduced the drug in Britain, Denmark, Finland, Ireland, Germany and Austria, as well as Norway and Argentina.

Vaccines

Bavarian Nordic reports progress in new smallpox vaccine program

Bavarian Nordic reported that it is in continuing dialogue with Department of Health and Human Services (HHS) officials on its proposal to supply the government with its Imvamune smallpox vaccine under the Project BioShield program.

While the timing of an award decision is not known, intensive efforts are underway to conclude the process, according to information the company has received from government officials. Earlier in the year, the government announced plans to acquire a new smallpox vaccine for persons who are immune-compromised and at risk for developing serious complications from the smallpox vaccine currently stockpiled.

Bavarian Nordic’s Imvamune smallpox vaccine is being developed for immune-compromised persons who may experience serious side effects from the traditional vaccine currently stockpiled by the U.S. government. This group includes children and the elderly, persons with eczema, and those with compromised immune systems from HIV/AIDS and other conditions.

Bavarian Nordic stated that more than 1,200 persons, including healthy volunteers, people with atopic dermatitis and those with HIV infection, have been vaccinated in three additional Phase II trials with Imvamune without serious or unexpected side effects. Safety data generated from these studies are a key requirement for filing and receiving an Emergency Use Authorization for Imvamune in the USA. A separate Phase II study with Imvamune in 151 HIV-infected persons has also been completed. Data from the main study will be reported at year-end 2006 and follow-up data in mid-2007.

The company's research facility in Germany has been granted Good Laboratory Practice (GLP) status by European authorities. Bavarian Nordic is now able to commence pivotal animal studies to further support the registration of Imvamune. Bavarian Nordic's manufacturing facility in Kvistgaard, Denmark, has also been approved by European authorities for the manufacture of sterile vaccines for use in clinical trials and emergency use in accordance with EU cGMP requirements. Bavarian Nordic is now able to manufacture smallpox vaccines for any order placed by the U.S. government or other governments for emergency use.

Researchers hope to kill many flus with one shot

 

At least 28 bird flu vaccines are under development by 13 different companies worldwide, according to the International Federation of Pharmaceutical Manufacturers & Associations. But while most drug companies design flu vaccines to generate antibodies that neutralize hemagglutinin and neuraminidase, which are likely to mutate, Dynavax Technologies in Berkeley, CA, has developed an influenza vaccine that targets two common flu proteins, the nucleoprotein and matrix protein, which tend to remain stable.

According to an article in the “San Mateo Times,” Dynavax believes that if some bird flu virus proteins mutate, their vaccine still would be effective against the proteins that do not change.

The Dynavax vaccine, like all bird flu vaccines, is in an early stage of development. But on Oct. 20, the company presented data at the Second International Conference on Influenza Vaccines for the World in Vienna that showed it was effective in mice and baboons. If the vaccine proves effective in people, it could be used for bird flu or seasonal flu. However, Dynavax plans to give both its vaccine and a standard vaccine that targets the mutating proteins as a safeguard.

Scientists at Vical Inc. in San Diego have reported progress with a similar vaccine, and researchers at the University of Bath in England are trying to develop mutation-resistant versions of anti-viral drugs, such as Tamiflu, which would be used to treat people already infected with bird flu.

Most people have at least a degree of immunity to seasonal flu, because they have been exposed to the virus at some time in their lives. But because bird flu is new, no such previously developed immunity exists. As a result, fairly large dosages of bird flu vaccine would be required to provide protection against the virus.

Novartis AG, which acquired Chiron and its Emeryville, CA, vaccine research facilities earlier this year, is adding boosters called adjuvants to its bird flu vaccines to initiate greater immune response. But even with boosters, some bird flu vaccines tested so far require high doses to generate an adequate immune response. However, GlaxoSmithKline Plc of England announced in July that its adjuvant-boosted vaccine triggered a strong immune reaction in about 80% of the 400 people who received it in a study.

Yet another concern is how to manufacture enough doses of bird flu vaccine quickly for the billions of people around the world who might need it. The typical method of making flu vaccines, which partly involves growing the virus in fertilized chicken eggs, would require vaccine manufacturers to obtain millions of eggs on short notice. However, the virus could kill many of the chickens counted on to produce those eggs, and greatly increased egg production requires substantial advance notice to farmers.

To avoid that problem, federal authorities have awarded Novartis and MedImmune a total of nearly $400 million over the next five years to make vaccines from a process using mammal cell cultures. The ingredients for such cultures can be stored in freezers and be instantly available in the event of a health emergency. They also tend to be less bulky than eggs.  Cell-based vaccines also seem to work as well as those derived from eggs, according to data Novartis presented Oct. 19 at the Vienna flu conference.

 

FDA management

 

Stephen Mason to join FDA’s Office of Legislation

 

Stephen Mason, a former Director of Government Relations at the Generic Pharmaceutical Association (GPhA) is joining FDA as a Senior Advisor in the agency’s Office of Legislation, effective Nov. 13.

 

In this role, Mason will work closely with David Boyer, Assistant Commissioner for Legislation, on a wide variety of issues pending before Congress, most notably generic drug legislation.

 

Mason comes to FDA after a diverse career in both regulated industry and on Capitol Hill. Prior to joining GPhA, Mason held several other positions, including Legislative Aide to Congressman John Ensign.  In this position he directed legislative issue management and fostered policy development on an array of issues, including health care. He earned a Bachelor of Science, Business Administration-Finance at Oakland University in Rochester, MI.

 

People

 

Renowned genetics team moves from Duke to University of Miami

Genetics researchers Jeffery Vance and Margaret Pericak-Vance will be moving from Duke University to the University of Miami. The husband-and-wife team discovered genes associated with diseases such as Alzheimer's, Parkinson's and macular degeneration while running Duke's Center for Human Genetics. They plan to continue searching for genetic risk factors for a wide range of common diseases.

A group of about 20 researchers will be moving with the Vances, and is expected to bring with it millions of dollars in annual funding from NIH.

R&D

 

Melior announces research collaboration with Merck

Melior Discovery announced on Nov. 7 that it has signed a research collaboration with Merck & Co. to evaluate the activity of select Merck neuroscience compounds utilizing elements of Melior's in vivo Indication Discovery platform. Under the terms of the agreement Merck will pay undisclosed fees for priority access to aspects of Melior's exclusively licensed platform.

Melior Discovery is using its Indication Discovery platform of multiplexed in vivo models to both build an internal pipeline of development candidates and to share this capability with pharma and biotechnology company partners. In the former case, the Company is identifying “privileged” compounds that have been discontinued by other firIn its partnered arrangements, Melior offers pharmaceutical partners an approach to expand their late-stage pipelines with high-quality drug candidates that originated from internal R&D efforts.

Avalon Pharmaceuticals initiate drug discovery program for the survivin pathway

Avalon Pharmaceuticals, a biopharmaceutical company focused on the discovery and development of small molecule therapeutics, has announced the initiation of a drug discovery program for the survivin pathway, an important and intractable cancer pathway. Survivin is overexpressed in multiple tumor types, including breast, lung, prostate, pancreatic and colon cancers. Survivin is cancer selective, as it is broadly expressed in most tumor types but undetectable in most normal adult cells.

The company’s AvalonRx technology identifies potential therapeutics based upon their ability to modulate pathways or targets within living cells.  Avalon's pipeline now includes AVN944, an IMPDH inhibitor in Phase I clinical trials for hematological malignancies; Beta-catenin and Aurora pathway inhibitor programs, which are in late-stage lead candidate optimization; and the new discovery program for survivin.  

Trial Updates

Adolor and partner GlaxoSmithKline said FDA has asked for more safety data, including an analysis of "serious cardiovascular events," from an ongoing clinical trial of Entereg, an experimental drug for treatment of postoperative ileus. FDA issued a second “approvable” letter for Entereg, but requested 12-month safety data, as well as a risk management plan to monitor the drug for serious side effects, if approved. FDA issues approvable letters when the agency wants more information on drugs it believes can be approved. For more details see: http://www.therapeuticsdaily.com/news/article.cfm?contentValue=388444&contentType=newsarchive&channelID=29

AstraZeneca announced its intention to expand the development plan for CytoFab, a treatment for severe sepsis, with the addition of a 480-patient Phase II study program. Consultations with regulators in the U.S. and EU confirmed that a single Phase III study could be sufficient for regulatory approval. To meet the regulatory needs of both agencies, AstraZeneca must implement a Phase II study program to support the single global Phase III study.  Data from Phase II will be used to more accurately estimate the number of patients required and confirm the appropriate dose for the Phase III study, as well as providing further supporting efficacy and safety data. The Phase II program will start in the second half of 2007 and should last up to 21 months. It will be immediately followed by the initiation of the Phase III study in the US, EU and Japan. For more details see: http://www.therapeuticsdaily.com/news/article.cfm?contentvalue=1142730&contenttype=sentryarticle&channelID=31

Elbit Medical Imaging announced that its subsidiary, Gamida Cell, developer of stem cell therapeutics, has reached an agreement under a Special Protocol Assessment (SPA) with FDA on the design of the global, pivotal, historical controlled, registration study of StemEx for the treatment of hematological malignancies. Gamida Cell is developing StemEx in a Joint Venture with Teva Pharmaceutical Industries Ltd. In response to the SPA application, FDA responded that the design and planned analysis of the study sufficiently address the study's objectives and that this study is adequately designed to provide the necessary data that, depending upon outcome, could support a license application submission. StemEx may provide an alternative source of stem cells for these patients by enabling the use of cord blood for transplantation. StemEx is composed of ex-vivo expanded cord blood stem/progenitor cells, which are transplanted in combination with non-expanded cells from the same cord blood unit. The Phase I/II study of StemEx conducted at the M. D. Anderson Cancer Center in Texas, showed safety and trends of efficacy. StemEx was granted an FDA Orphan Drug designation in March 2005. For more details see: http://media.prnewswire.com/en/jsp/latest.jsp?beat=BEAT_HEALTHCARE&view=LATEST&resourceid=3333191

FlowCardia announced the enrollment of the first patient into the 10-hospital, 85-patient PATRIOT (Peripheral Approach To Recanalization In Occluded Totals) U.S. pivotal study. This study is designed to determine the safety and efficacy of the Crosser 14 and Crosser 18 Catheters for CTO recanalization in the upper and lower legs, which use high frequency vibration to quickly cross CTOs, allowing for subsequent plaque debulking, balloon angioplasty and stent placement. For many patients with chronic occlusions in the legs, this approach to CTO recanalization could eliminate the need for potentially traumatic bypass surgery or amputation. FlowCardia also announced FDA 510(k) submission for the Crosser 14 coronary platform. The data used to support the coronary submission came from FlowCardia's 19-hospital, 125-patient U.S. FACTOR (FlowCardia's Approach to Chronic Total Occlusion Recanalization) pivotal study. The FACTOR Study was designed to assess the safety and efficacy of the Crosser catheter for chronically occluded coronary artery recanalization. For more details see: http://media.prnewswire.com/en/jsp/latest.jsp?resourceid=3331027&access=EH

Morphotek announced that FDA has granted orphan drug status to MORAb-009, a monoclonal antibody, for the indication of pancreatic cancer. MORAb-009 is an antibody that recognizes mesothelin, a cell surface glycoprotein overexpressed in a number of cancers. Researchers at the National Cancer Institute (NCI) and Johns Hopkins University have independently validated the association of this protein in cancer and the therapeutic potential of drugs that can specifically target it. Studies have demonstrated a high correlation of mesothelin expression with pancreatic, mesothelioma, ovarian and non-small cell lung carcinomas, as well as several epithelial-based cancers. For more details see: http://media.prnewswire.com/en/jsp/latest.jsp?beat=BEAT_HEALTHCARE&view=LATEST&resourceid=3334581

Scientific Intake announced on Nov. 7 that it has completed enrollment of 190 subjects for its multi-site clinical trial of a new weight loss device, and will seek FDA market clearance for the device. Scientific Intake's device simulates a physical condition linked with thinness called Torus Palatinus. The device contains a wireless microsensor linking patients and providers for remote monitoring of compliance, behavior change and progress. The mode of action of the investigative product physically increases savoring, reduces bolus size, slows intake and allows the body's built-in defense mechanism, the satiety response, to trigger. Device users in earlier studies reported feeling satisfied while food intake was reduced by 23%. Study completion is scheduled for spring of 2007, Longley said, and will be followed by 510(k) de novo submission to FDA. For more details see: http://media.prnewswire.com/en/jsp/latest.jsp?resourceid=3334952&access=EH

VaxGen announced that FDA has notified the biopharmaceutical company that its second round of Phase II trials for an investigational anthrax vaccine must be postponed. Brisbane-based VaxGen said CBER issued a “hold” notice because the company's data is insufficient to show the product is stable enough to resume clinical testing. In the notification, the agency expressed concerns that the vaccine's potency could decline during the immunization phase of the trial. VaxGen said it will meet with FDA to discuss ways to satisfy requirements and resume testing. The company earlier won an $877.5 million contract by the U.S. Department of Health and Human Services to provide 75 million doses of a modern anthrax vaccine for civilian biodefense. For more details see: http://www.therapeuticsdaily.com/news/article.cfm?contentvalue=1143000&contenttype=sentryarticle&channelID=31

Trial Briefs

Allos Therapeutics announced the presentation of updated results from its Phase II multi-center study of Efaproxyn (efaproxiral) in patients with unresectable non-small cell lung cancer (NSCLC) receiving sequential chemoradiotherapy (S-CRT). Results of a five-year survival analysis indicated that patients in the Efaproxyn study exhibited superior survival to patients with similar characteristics in the RTOG 94-10 study. Median survival of patients treated in the Efaproxyn study was 20.6 months as compared to a median survival of 13.3 months for matched cases in the S-CRT arm of the RTOG 94-10 study and 16.9 months in the concurrent chemoradiotherapy (C-CRT) arm of the RTOG 94-10 study. The Kaplan- Meier estimates of five-year survival rates for matched cases were 19% in the Efaproxyn study and 10% in both the S-CRT and C-CRT arms of the RTOG 94-10 study. Allos is currently conducting a Phase I study of Efaproxyn in patients with locally advanced, unresectable (Stage III) NSCLC receiving C-CRT. Efaproxyn is the first synthetic small molecule designed to sensitize hypoxic areas of tumors during radiation therapy by facilitating the release of oxygen from hemoglobin and increasing the level of oxygen in tumors, an essential element for the effectiveness of radiation therapy. For more details see: http://media.prnewswire.com/en/jsp/latest.jsp?resourceid=3333598&access=EH

Bayer reported findings of a new study showing that when persons with diabetes use miscoded blood glucose meters to determine how much insulin to take, significant errors in insulin dose can result, leading potentially to short- and long-term health complications. The results were presented at the Sixth Annual Diabetes Technology Meeting in Atlanta, GA. In this study, for certain miscoded meters, the probability of insulin error of plus or minus two units of insulin was 50% as compared to 8% for correctly, manually coded meters. The probability of insulin dose error of plus or minus three units of insulin was 23% for the miscoded meters but only 0.5% for the manually correctly coded meters. Coding is the process by which a blood glucose meter is matched to each new box of test strips being used, either by inserting a code strip or code chip into the meter, or by entering a code number into the meter. If this step is not performed, the meter may give inaccurate results. The study findings also showed that auto-coded meters gave more accurate blood glucose values than meters that had been correctly coded manually. The probability of plus or minus one unit and plus or minus two units of insulin could be as high as 35.4% and 1.4% respectively. However, with the auto-coded meters, there were no calculated insulin dose errors above plus or minus two units. For more details see:

http://media.prnewswire.com/en/jsp/latest.jsp?beat=BEAT_HEALTHCARE&view=LATEST&resourceid=3333413

 

Biopure announced that the independent Data and Safety Monitoring Board (DSMB) for the company's Phase II clinical trial of Hemopure [hemoglobin glutamer - 250 (bovine)] in trauma patients has completed its first scheduled interim analysis of blinded study data and recommended that the trial continue without modification. The DSMB reviewed mortality and other safety data from the first 21 patients enrolled in this single-center trial at Johannesburg Hospital Trauma Unit in South Africa. The 50-patient, single-blind Phase II trial is designed to assess the safety and tolerability of Hemopure in a hospital setting for emergency treatment of unstable patients who have significant blood loss as a result of blunt or penetrating trauma. For more details see:

http://media.prnewswire.com/en/jsp/latest.jsp?beat=BEAT_HEALTHCARE&view=LATEST&resourceid=3334263

 

Boston Scientific presented a four-year update of its key randomized, controlled clinical trials (TAXUS II, IV, V and VI) in 3,445 patients, including 840 diabetic patients, comparing the Taxus stent to bare-metal control stents.  The diabetic patient subset accounts for more than one-quarter of all coronary interventional procedures in the United States. Although diabetic patients generally have more long-term complications than interventional cardiology patients as a whole, in this meta-analysis the diabetic patients assigned to receive the Taxus stent had equal or lower all-cause mortality at four years compared to patients assigned to receive a bare-metal control stent. The Taxus stent diabetic patients also experienced a 50% relative decrease in the need for repeat procedures to treat restenosis within the stent. In addition, an analysis of 10 studies with a total of 4,187 diabetic patients showed that patients who received the Taxus stent experienced a 25% relative reduction in the need for repeat procedures to treat restenosis, compared to those who received the Cypher stent sold by Johnson & Johnson's Cordis unit. The company is currently sponsoring the collection of clinical data to support an application to FDA to expand the Taxus stent's labeled indications for use in the United States to include diabetic patients. http://media.prnewswire.com/en/jsp/latest.jsp?beat=BEAT_HEALTHCARE&view=LATEST&resourceid=3333267

Callisto Pharmaceuticals announced the first dosing of patients in a multi-center, open-label Phase II clinical trial of Atiprimod to treat low- to intermediate-grade neuroendocrine carcinomas, including advanced carcinoid cancers. The primary objective of the trial is to evaluate efficacy of Atiprimod in patients with metastatic or unresectable cancer and who have either symptoms, despite standard therapy (octreotide) or progression of neuroendocrine tumors. Patients are required to complete two weeks of a symptoms diary to establish their symptoms baseline before commencing Atiprimod dosing. A maximum of 40 evaluable patients will be enrolled in this trial. Efficacy evaluations will include the measure of target lesions (per RECIST), and the quantization of symptom relief. Further details of this trial can be found at www.clinicaltrials.gov  For more details also see: http://media.prnewswire.com/en/jsp/latest.jsp?beat=BEAT_HEALTHCARE&view=LATEST&resourceid=3334550

CardioDynamics announced the publication of a study in the Fall 2006 edition of the “American Heart Hospital Journal” showing that use of impedance cardiography (ICG) was cost-effective in both the short- and long-term when compared to standard care treatment of patients with uncontrolled hypertension.  In the previously published CONTROL trial, use of ICG in the treatment of uncontrolled hypertension resulted in an 8mm Hg greater systolic blood pressure reduction and a 7mm Hg greater diastolic blood pressure reduction than standard care. The short-term cost-effectiveness analysis demonstrated that ICG care’s incremental cost per mm Hg reduced was $20 for systolic blood pressure (44% less than standard care's $36 cost per mm Hg reduced) and $23 for diastolic blood pressure (71% less than standard care's $79 cost per mm Hg reduced). The long-term cost-effectiveness analysis showed that even if only a fraction of the short-term blood pressure advantages with ICG were sustained, patients treated with ICG would likely experience fewer cardiovascular events. To obtain copies of the publication, please access the following link: http://www.lejacq.com/downloads/3rdPartyLinkOut/CrdDyn-HH5728-Ferrario.pdf  For more details see: http://media.prnewswire.com/en/jsp/latest.jsp?beat=BEAT_HEALTHCARE&view=LATEST&resourceid=3333749

Cellgate announced the initiation of a Phase II clinical trial of its lead compound, CGC-11047, a polyamine analog designed to halt cell growth and induce apoptosis. The Phase II clinical trial will enroll approximately 40 patients with metastatic hormone refractory prostate cancer who have not received prior chemotherapy. The primary endpoint for the study is efficacy based on PSA response. Safety, tolerability and time to progression will also be evaluated as part of the Phase II study. CGC-11047 will be administered intravenously as a single-agent by infusion once weekly for three weeks over a four-week cycle at a dose of 200 mg. In two separate Phase I clinical trials, a total of 20 patients (with a variety of advanced solid tumors) have been treated with CGC-11047 to date. CGC-11047 has been well tolerated with no dose-limiting toxicities reported. Preclinical in vitro studies have shown that CGC-11047 is cytotoxic to several standard tumor cell lines. For more details see:

http://www.therapeuticsdaily.com/news/article.cfm?contentValue=1135299&contentType=sentryarticle&channelID=28

 

Cordis announced that studies support the long-term safety and efficacy of the Cypher Sirolimus-eluting coronary stent in a variety of coronary conditions, including those with diabetes.  Data from the ARTS II trial, which compared the use of the Cypher stent to bypass surgery, showed comparable mortality rates among diabetic patients treated with either bare metal stents or the Cypher stent. For more details see:

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Digene reported that a Danish Cancer Society study has found that for women age 40 and older, testing for human papillomavirus (HPV) is more effective in predicting cervical cancer risk than the traditionally used Pap smear. The study, which followed more than 10,000 women for 10 years, was published in the Nov. 1 issue of “Cancer Research.” Researchers used Digene’s Hybrid Capture 2 (hc2) High-Risk HPV DNA Test, the only FDA-approved test for potentially cancer-causing types of HPV.  The study revealed that while HPV infection in younger women is more frequent, it is usually transient, while HPV infection in women age 40 or older is less common but more persistent, putting them at higher risk of developing abnormal cells. As many as 21% of older women whose Pap smears were initially normal but who were found to have HPV later developed significant abnormal cells on their cervix. In contrast, only 1.7% of women whose HPV and Pap tests were normal later developed abnormalities. For more details see:

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EntreMed announced commencement of a multi-center, Phase II clinical trial with its clinical-stage drug candidate, Panzem NCD (2ME2 or 2-methoxyestradiol), in patients with recurrent or resistant epithelial ovarian cancer. The Hoosier Oncology Group, headquartered in Indianapolis, will conduct the study. Primary objectives for this single-agent study will be to assess the safety, pharmacokinetics, tumor response rate and progression-free survival (PFS) in ovarian cancer patients receiving orally administered Panzem NCD. Patients with recurrent or resistant epithelial ovarian cancer will be treated. EntreMed received orphan drug designation for 2ME2 from FDA for treatment of ovarian cancer. For more details see: http://www.therapeuticsdaily.com/news/article.cfm?contentValue=1135198&contentType=sentryarticle&channelID=28

 

Hana Biosciences announced the initiation of a multi-center Phase II clinical trial with Talvesta (talotrexin) for injection in adult patients with relapsed or refractory acute lymphoblastic leukemia (ALL). The primary objective of this portion of an ongoing Phase I/II open-label study is to evaluate the complete remission rate (CR/CRp) of Talvesta in relapsed or refractory ALL patients. Secondary objectives are to evaluate the safety and tolerability of Talvesta in this setting as well as duration of complete remission and overall survival. Talvesta is a novel, nonpolyglutamable antifolate drug that targets DHFR. Talvesta has demonstrated enhanced anti-tumor activity in a broad spectrum of preclinical studies by targeting the enzyme DHFR to prevent DNA synthesis in tumor cells and inhibit tumor growth. In May 2006, FDA granted orphan drug designation for Talvesta in patients with ALL. Talvesta is also being studied in a Phase I trial in solid tumors and a Phase I/II trial in non-small cell lung cancer (NSCLC). For more details see:  http://www.therapeuticsdaily.com/news/article.cfm?contentvalue=1134367&contenttype=sentryarticle&channelID=28

ImClone Systems and Bristol-Myers Squibb reported mixed results from a pair of randomized Phase III trials of Erbitux (cetuximab) in 572 patients with metastatic colorectal cancer. A randomized, multi-center, Phase III trial of Erbitux and best supportive care versus best supportive care alone met its primary efficacy endpoint by showing a statistically significant improvement in overall survival in metastatic colorectal cancer whose disease was refractory to all available chemotherapy. But a second Phase III trial of Erbitux plus irinotecan versus irinotecan alone did not meet its primary endpoint of overall survival, though secondary endpoints of progression-free survival and response rate “strongly favored” the Erbitux combination. The study was conducted by the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) in collaboration with the Australasian Gastro-Intestinal Trials Group (AGITG).  A second Phase III, randomized study, known as the Erbitux Plus Irinotecan in Colorectal Cancer (EPIC), compared irinotecan to irinotecan plus Erbitux in approximately 1,300 patients whose disease was not responding to first-line oxaliplatin-based chemotherapy. Secondary efficacy endpoints (progression free survival, response rate) strongly favored the combination of Erbitux plus irinotecan over irinotecan alone; however, the primary endpoint (overall survival) was not met. Efforts to interpret these confounded results are ongoing. For more details see:

http://www.therapeuticsdaily.com/news/article.cfm?contentValue=1144247&contentType=sentryarticle&channelID=26

 

Infinity Pharmaceuticals announced preliminary results from an open-label Phase I clinical study of IPI-504 in patients with Gleevec-resistant metastatic gastrointestinal stromal tumors (GIST). IPI-504, Infinity's lead oncology drug candidate, is a proprietary small molecule inhibitor of Heat Shock Protein 90 (Hsp90) that is being jointly developed by Infinity and MedImmune. This trial is being conducted at the Dana-Farber Cancer Institute in Boston, MA. To date, 20 GIST patients have received IPI-504 at dose levels ranging from 90 to 400 mg/m2. Patients included in the study were heavily pre-treated and nearly all had failed prior therapy with Sutent as well as Gleevec, two approved therapies for the treatment of GIST. IPI-504 has been well tolerated to date at all dose levels tested, and a maximum tolerated dose has not yet been identified. Investigators have observed evidence of biological activity for IPI-504 using positron emission tomography imaging, or PET. For more details see:

http://www.therapeuticsdaily.com/news/article.cfm?contenttype=sentryarticle&contentvalue=1144541&channelID=28#

 

Kaiser Permanente reported that its study of 24,600 patients in Northern California revealed that cholesterol-lowering drugs might reduce the risk of death and hospitalization for some people with heart failure. Heart failure patients who took statins were 24% less likely to die and 21% less likely to be hospitalized than patients not given statins, according to the study, which appeared in the “Journal of the American Medical Association.” The study involved 24,600 heart failure patients in Northern California Kaiser facilities from 1996 through 2004. None had used statins before; half initiated statin therapy. The median length of statin therapy was 2.5 years. The study showed that patients on statins did better than those who did not take the drug, even after adjusting for other factors, such as complementary drugs. The Kaiser study was funded with a grant from Amgen, a pharmaceutical company. For more details see:

http://www.therapeuticsdaily.com/news/article.cfm?contenttype=sentryarticle&contentvalue=1136067&channelID=26#

 

Karolinska Institute in Stockholm announced that a study of seven years of patient data in the United Kingdom general practice database indicates that the use of drugs that reduce stomach acid, such as H2 blockers (Zantac, Tagamet) and proton pump inhibitors (Prilosec), do not increase the risk of cancer of the esophagus or stomach. The study reported was reported in the November 2006 issue of the journal “Gut.” The research team compared 287 patients with esophageal cancer and 522 with stomach cancer with 10,000 randomly selected subjects without cancer. The authors found some conditions such as acid reflux disease, hiatal hernia and Barrett’s esophagus were associated with an increased risk of stomach and esophagus cancer. However, no apparent cancer risk was seen with other conditions, including peptic ulcer, gastritis and indigestion. They found no evidence that the drugs themselves increased the risk. For more details see:

http://today.reuters.com/news/articlenews.aspx?type=healthNews&storyID=2006-11-02T031023Z_01_KNE211361_RTRUKOC_0_US-STOMACH-ACID.xml&WTmodLoc=HealthNewsHome_C2_healthNews-6

 

Maxygen announced that Roche has initiated a Phase Ia clinical trial in New Zealand to evaluate the safety, tolerability, pharmacokinetic and pharmacodynamic profile of Maxy-alpha, a next-generation interferon alpha for the treatment of hepatitis C virus infection. The trial is a double-blind, dose-escalation, controlled study of a single subcutaneous administration of Maxy-alpha in healthy volunteers with both placebo and Pegasys (peginterferon alfa-2a (40KD)) control groups. Maxy-alpha, also known as R7025, is a novel PEGylated interferon alpha variant created through the use of Maxygen's proprietary MolecularBreeding directed molecular evolution technologies. Maxy-alpha has been designed to have more anti-viral activity against the hepatitis C virus and be more effective in stimulating immune responses to help combat the infection. For more details see:

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MedImmune announced preliminary results from a Phase III pivotal study showing that Numax met its primary endpoint of non-inferiority by reducing the incidence of hospitalizations caused by respiratory syncytial virus (RSV) in infants at high risk for serious RSV disease by 26% when compared to Synagis (palivizumab). The data also indicate that Numax showed superiority over Synagis in a secondary endpoint by reducing the incidence of RSV-specific medically attended outpatient lower respiratory infections (LRI) by approximately