WASHINGTON, May 12 — A cardiologist who chairs an FDA advisory panel joined a lineup of witnesses asking Congress to eliminate manufacturers’ blanket immunity from lawsuits over faulty medical devices that were preapproved by the FDA.

“Unanswered questions regarding device safety and effectiveness often remain at the time of FDA approval,” William Maisel, M.D., chairman of the agency’s Circulatory Devices Committee, testified on Tuesday.

Dr. Maisel, of Beth Israel Deaconess Medical Center in Boston, said FDA approval doesn’t mean a device won’t malfunction.

Noting that 10 million patients have these implanted devices, he said, “It is apparent additional consumer safeguards are needed.”

He testified before a House Energy and Commerce Subcommittee in favor of the Medical Devices Safety Act of 2009, which would provide patients with legal recourse if they are injured by a malfunctioning implanted device.

Under an odd twist of U.S. law, drug companies are liable for damages if their products cause harm, but many device makers are not.

In fact, if a medical device received premarket approval from the FDA, the manufacturer is protected from liability, thanks to a 2008 Supreme Court interpretation of a 30-year-old law making the FDA the final arbiter of device safety.

In that 8-1 decision (Reigel v. Medtronic), the Supreme Court ruled that if a device received premarket approval from the FDA, individuals injured by the device may not sue the manufacturer for damages.

As a result, lower courts threw out 1,400 lawsuits against device makers, according to Rep. Henry A. Waxman (D-Calif.), chairman of the full House Energy and Commerce committee.

“It is time for Congress to act properly to correct this clear judicial overreach,” added Rep. John D. Dingell (D-Mich.).

Drug companies do not enjoy the same immunity. In March, the Supreme Court ruled 6-3 in Wyeth v. Levine that FDA approval of a drug does not shield its maker from lawsuits brought by patients injured by use of the drug.

(See Supreme Court Tells Drugmakers ‘Label Is No Shield’)

The bill heard Tuesday, sponsored by Rep. Frank Pallone (D-N.J.), would put the two industries on a level liability playing field.

No representatives from the device industry were on the witness panel.

But Republicans on the committee and a representative from the Advanced Medical Technology Association (AdvaMed) said device companies do not have true “blanket immunity” from legal action.

They are still subject to criminal penalties in certain cases, Brett Loper, director of government affairs for AdvaMed, told MedPage Today after the hearing.

Rep. Nathan Deal (R-Ga.) argued that the majority of state claims are still allowed because the current law shields only device companies that received premarket approval. They account for just 2% of all devices on the market, he said.

Most devices are approved through a process known as 510(k), which grants approval if a device is “substantially similar” to one already on the market. Their manufacturers are not shielded from liability even if they are identical to products that are.

Although devices that are shielded from lawsuits represent only a small proportion of the total market, their 10 million owners deserve legal protection in the event a “manufacturer fails to produce a product that is as reliable as it should be,” said Dr. Maisel.

Democrats on the panel said legislation is necessary because without a risk of liability, makers of the highest-risk devices — the class III devices which require premarket approval — have no incentive to report device malfunctions to the FDA.

But Republicans on the panel said the bill would stifle innovation because device companies would operate in fear of lawsuits.

“No company would ever create a device if one error meant total ruin for the company,” said Rep. Michael Burgess, M.D. (R-Tex.), an obstetrician-gynecologist.

Related Article(s):

• Supreme Court Tells Drugmakers ‘Label Is No Shield’

WASHINGTON, May 12 — The FDA is investigating a possible link to heparin in the deaths of two Delaware residents who suffered cerebral hemorrhages following heparin treatment.

The deaths of a 71-year-old man and a 64-year-old woman occurred over the weekend. A third patient, a 68-year-old man, remains hospitalized. All three became ill after taking heparin last week, according to officials at Beebe Medical Center in Lewes, Delaware.

The Associated Press reported that the 71-year-old man died after being transferred to Christiana Hospital in Newark, Delaware, while the woman was transferred to the University of Maryland hospital in Baltimore, where she died.

The third patient remains hospitalized at Christiana Hospital. All three suffered cerebral hemorrhages.

Beebe Medical Center said the patients were treated with heparin supplied by Baxter International.

Baxter, which is the largest supplier of heparin in the U.S., was at the center of the worldwide heparin contamination, which caused hundreds of allergic reactions and a number of deaths in 2008.

In that investigation, the FDA traced the problem to oversulfated chondroitin sulfate in raw material from China.

Baxter said the heparin given the Delaware patients was made from raw material supplied by Pfizer, which gets its active pharmaceutical ingredients from a supplier in Ohio.

The Beebe Medical Center informed Baxter on Friday that three patients had become ill, and the company informed the FDA.

Both Baxter and the FDA have sent teams to Delaware to investigate the cases.

Related Article(s):

• Contaminated Heparin Confirmed as Cause of Allergic Reactions
  

Nearly one-third of cancer research published in high-impact journals disclosed a conflict of interest, according to a new study from researchers at the University of Michigan Comprehensive Cancer Center.

The most frequent type of conflict was industry funding of the study, which was seen in 17 percent of papers. Twelve percent of papers had a study author who was an industry employee. Randomized trials with reported conflicts of interest were more likely to have positive findings.

“Given the frequency we observed for conflicts of interest and the fact that conflicts were associated with study outcomes, I would suggest that merely disclosing conflicts is probably not enough. It’s becoming increasingly clear that we need to look more at how we can disentangle cancer research from industry ties,” says study author Reshma Jagsi, M.D., D.Phil., assistant professor of radiation oncology at the U-M Medical School.

The researchers looked at 1,534 cancer research studies published in prominent journals. Results of this current study appear online in the journal Cancer.

“A serious concern is individuals with conflicts of interest will either consciously or unconsciously be biased in their analyses. As researchers, we have an obligation to treat the data objectively and in an unbiased fashion. There may be some relationships that compromise a researcher’s ability to do that,” Jagsi says.

For example, she says, researchers might design industry-funded studies in a way that’s more likely to produce favorable results. They might also be more likely to publish positive outcomes than negative outcomes.

“In light of these findings, we as a society may wish to rethink how we want our research efforts to be funded and directed. It has been very hard to secure research funding, especially in recent years, so it’s been only natural for researchers to turn to industry. If we wish to minimize the potential for bias, we need to increase other sources of support. Medical research is ultimately a common endeavor that benefits all of society, so it seems only appropriate that we should be funding it through general revenues rather than expecting the market to provide,” Jagsi says.

Methodology: The researchers looked at all original clinical cancer research published in five top oncology journals and three top general medical journals in 2006. The journals included were the New England Journal of Medicine, The Journal of the American Medical Association, Lancet, The Journal of Clinical Oncology, The Journal of the National Cancer Institute, Lancet Oncology, Clinical Cancer Research and Cancer.

Articles were analyzed to determine declared funding sources and conflicts of interest. A conflict of interest was identified if it was explicitly declared by the authors, if an author was an employee of industry at the time of publication, or if the study had industry funding.

Additional authors: Nathan Sheets; Aleksandra Jankovic, M.S.; Amy R. Motomura; Sudha Amarnath; and Peter A. Ubel, M.D.

Reference: Cancer, published online May 11, 2009; scheduled for print publication June 15, 2009

Source:
Nicole Fawcett

University of Michigan Health System

Interim results of Abbott’s PROGRESS study showed that Kaletra® combined with raltegravir suggested a more rapid initial viral load decline when compared to a traditional triple-drug combination therapy of Kaletra and Truvada®.1 PROGRESS is an open-label, 96-week evaluation of the safety and efficacy of Abbott’s HIV protease inhibitor Kaletra (lopinavir/ritonavir) in combination with raltegravir, the integrase inhibitor manufactured by Merck, compared to Kaletra and the nucleoside reverse transcriptase inhibitor (NRTI) Truvada (tenofovir and emtricitabine) in antiretroviral-naive, HIV-1-infected patients. Abbott conducted an eight-week analysis to compare rates of viral decay between the two regimens. The study results were presented at the 15th Annual Conference of the British HIV Association (BHIVA).

“These interim results from the PROGRESS study are the first data to suggest that more rapid viral suppression may be possible with a dual regimen that includes Kaletra and raltegravir versus a standard triple-therapy regimen,” said Scott C. Brun, M.D., divisional vice president, infectious diseases and immunology development, Global Pharmaceutical Research and Development, Abbott. “Lowering a patient’s viral load to an undetectable level and maintaining viral load suppression are key success markers for patients beginning antiretroviral treatment.”

Other key findings of the study include:

A greater proportion of patients had HIV-1 RNA levels <40 copies/mL at weeks two, four and eight when treated with Kaletra and raltegravir compared with Kaletra and Truvada. Intent-to-treat results were similar to the observed data.

Both treatment groups had statistically significant mean increases from baseline in CD4+ T-cell count at weeks four and eight (p<0.001).

Overall, the incidences of treatment-emergent adverse events were similar between treatment groups. The most commonly-reported events in both treatment groups, regardless of severity or relationship to study drug, were gastrointestinal in nature, including diarrhoea, nausea and flatulence. Headache was also commonly reported and did not differ between groups.

Cholesterol elevations ?7.77 mmol/L were observed in 7 percent (seven out of 101 patients) of Kaletra and raltegravir patients and 3 percent (three out of 102 patients) of Kaletra and Truvada patients.

Triglyceride increases ?8.475 mmol/L were detected in 6 percent (six out of 101) of Kaletra and raltegravir patients, but were not observed in Kaletra and Truvada patients (p=.014).

Kaletra is a protease inhibitor and is always used in combination with other anti-HIV-1 medicines for the treatment of HIV-1 infection. Kaletra is indicated for adults and for children age two years and older.2 Raltegravir is an integrase inhibitor indicated for use in combination therapy in treatment-experienced adult patients who have HIV-1 that is resistant to multiple antiretroviral medications. The safety and efficacy of raltegravir have not been established in treatment-naïve adult patients or paediatric patients.3

The rapid viral suppression observed for Kaletra and raltegravir is consistent with the Merck 004 Study,4 in which raltegravir in combination with two NRTIs was shown to be as effective in suppressing viral load in treatment-naïve HIV-infected patients as efavirenz administered with two NRTIs in a triple-therapy regimen. In the study, viral decay rates were significantly higher for the raltegravir arm compared to the efavirenz arm.

“The initial PROGRESS results suggest that a nucleoside-free dual regimen may perform as well as the standard triple-therapy regimen,” said Jose Arribas, M.D., senior attending physician, HIV Unit, Hospital Universitario La Paz, Madrid, Spain.

About the PROGRESS Study

PROGRESS is an open-label 96-week evaluation of the safety and efficacy of Kaletra in combination with raltegravir, compared to Kaletra and Truvada in antiretroviral-naïve subjects.

The PROGRESS study combines Kaletra with raltegravir, an integrase inhibitor.

PROGRESS is a global, multicenter study of approximately 200 patients. The study is fully enrolled and 48-week data are planned for the first half of 2010.

Merck supplied raltegravir for the PROGRESS study.

The primary endpoints of the 96-week PROGRESS study evaluate the antiviral activity, safety and tolerability of the two regimens. Secondary endpoints include metabolic effects, fat distribution, time to loss of virologic response, incidence of resistance to each drug in the study and patient-reported outcomes.

More Information on Kaletra

Kaletra was studied for seven years in Abbott Study 720,5 one of the longest clinical trials for any antiretroviral agent, which was completed in April 2005.
The Kaletra tablet is the first and only co-formulated protease inhibitor tablet that does not require refrigeration and can be taken with or without food, two important factors in delivering HIV medicine, especially in developing countries.

More Information on Raltegravir

Raltegravir is the first medicine to be approved in a new class of antiretroviral drugs called integrase inhibitors.

Raltegravir is approved for use in combination with other antiretroviral agents for the treatment of HIV-1 infection in treatment-experienced adult patients who have evidence of viral replication and HIV-1 strains resistant to multiple antiretroviral agents.

The safety and efficacy of raltegravir have not been established in treatment-naïve adult patients or pediatric patients.

Raltegravir works by inhibiting the insertion of HIV-1 DNA into human DNA by the integrase enzyme. Inhibiting integrase from performing this essential function limits the ability of the virus to replicate and infect new cells. There are drugs in use that inhibit two other enzymes critical to the HIV-1 replication process - protease and reverse transcriptase - but raltegravir is the only drug approved that inhibits the integrase enzyme.

Abbott and HIV/AIDS

Abbott has been a leader in HIV/AIDS research since the early years of the epidemic. In 1985, the company developed the first licensed test to detect HIV antibodies in the blood and remains a leader in HIV diagnostics. Abbott retroviral and hepatitis tests are used to screen more than half of the world’s donated blood supply. Abbott has developed two protease inhibitors for the treatment of HIV.

Reference

1. Thomas Podsadecki, M.D., Min Tian, M.S., Linda Fredrick, M.S., Adebayo Lawal, M.D., Barry Bernstein, M.D. Lopinavir/Ritonavir (LPV/r) Combined With Raltegravir (RAL) Provides More Rapid Viral Decline Than LPV/r Combined With Tenofovir Disoproxil Fumarate/Emtricitabine (TDF/FTC) in Treatment-naïve HIV-1 Infected Subjects. 15th Annual Conference of the British HIV Association (BHIVA) • 1-3 April 2009 • Liverpool, UK

2. Kaletra Summary of Product Characteristics, 2007

3. Raltegravir Summary of Product Characteristics 2008

4. Martin Markowitz, MD,* Bach-Yen Nguyen, MD,† Eduardo Gotuzzo, MD,‡ Fernando Mendo, MD, et cal, Rapid and Durable Antiretroviral Effect of the HIV-1. Integrase Inhibitor Raltegravir as Part of Combination Therapy in Treatment-Naive Patients With HIV-1 Infection. Results of a 48-Week Controlled Study, J Acquir Immune Defic Syndr _ Volume 46, Number 2, October 1, 2007

5. R Murphy, B da Silva, F McMillan, C Hicks, J Eron, P Wolfe et al. Seven year follow-up of a lopinavir/ritonavir (LPV/r)-based regimen in antiretroviral-naïve subjects. Poster presentation at the 10th European AIDS Conference; Dublin, November 17-20, 2005 - Abstract #P7.9/3

Source
Abbott

View drug information on Kaletra Capsules and Oral Solution.

For men younger than 50 with prostate cancer, undergoing a radical prostatectomy can greatly increase their chances for long-term survival, according to a new study from Henry Ford Hospital.

Results from the study done on the National SEER database show that the surgical procedure improves the 5-, 10-, 15- and 20-year survival for younger patients, when compared with other standard treatments such as radiotherapy or watchful waiting.

“When given the choice between surgery, watchful waiting or external beam radiotherapy, patients younger than 50 with moderately and poorly differentiated prostate cancers have better long-term overall and cancer-specific survival when they opt for surgery,” says study author Naveen Pokala, M.D., an urologist with Henry Ford Hospital.

Based on findings from the study, Dr. Pokala and co-author Mani Menon, M.D., director of Henry Ford’s Vattikuti Urology Institute, strongly recommend retropubic radical prostatectomy - a surgical procedure that removes the entire prostate gland plus some of the tissue around it - as the treatment of choice for prostate cancer patients under the age of 50.

Prostate cancer affects one in six men in the United States during his lifetime, but according to the American Cancer Society only one in 35 will die of it.

Although the majority of all prostate cancer are diagnosed in men older than 65, its prevalence is growing among men younger than 50. In fact, about one in 10,000 men under the age of 40 will be diagnosed this year with prostate cancer.

To determine which treatment option offers the best chance for long-term survival for younger prostate cancer patients, Pokala and Menon studied more than 8,200 men under age 50 with prostate cancer.

Among the study group, 73 percent were white and about 22 percent were black. The mean age was 46, and over 70 percent had moderately and 22 percent had poorly differentiated cancers. Of the patients, 1,065 were managed with no definitive treatment (watchful waiting); 6,614 (79.9 percent) with radical retropubic prostatectomy; and 600 with external beam radiotherapy.

The cancer-specific survival in the NDT group was 78 percent at 16 years, in the radiation group was 63 percent at 17 years; and 94 percent in the radical prostatectomy at 21 years. On a subset analysis the outcome was significantly better after radical prostatectomy in patients with moderately and poorly differentiated prostate cancer.

Overall, the study shows the 5-year, 10-year, 15-year and 20-year overall survival and cancer specific survival is significantly increased in patients who were less than 50 years of age with moderately and poorly differentiated cancers in the surgery group.

The results were presented in Chicago at the recent American Urological Association’s annual meeting.

Source:
Dwight Angell

Henry Ford Health System

Arno Therapeutics, Inc., a clinical-stage biopharmaceutical company focused on oncology therapeutics, announced that the U.S.