DID - June 6, 2007 Issue

Vol. 6 No. 111

Industry Awaits Hearing on Patent Reform

The Senate Judiciary Committee will consider a patent law favored by the generic pharmaceutical industry this week.

The “Patent Reform Act of 2007,” S. 1145, was introduced in April by Judiciary Committee Chairman Patrick Leahy (D-Vt.) and Sen. Orrin Hatch (R-Utah). Its counterpart in the House, H.R. 1908, was introduced during the same month by Howard Berman (D-Calif.), chairman of the House Subcommittee on Courts, the Internet and Intellectual Property, and Rep. Lamar Smith (R-Texas).

This year’s version of the bill contains several significant changes from last year’s. Current legislation does not call for the elimination of the inequitable conduct defense, which is one of the ways generic companies can defend themselves in patent infringement suits. “Without this defense, brand companies would be allowed to preserve dubious patents that unreasonably prevent safe, effective and affordable generic drugs from reaching consumers,” the Generic Pharmaceutical Association (GPhA) said.

In addition, the bill does not seek to remove the “best mode” requirement, as had been previously proposed. This provision of patent law requires patent applications to contain a detailed description of the best way to produce the product. “Maintaining the best mode requirement is crucial to promoting efficient use of scientific resources,” GPhA noted.

Other industry groups have also taken interest in the bill. The Coalition for 21st Century Patent Reform — which counts among its members many brand pharmaceutical companies, including Pfizer, Merck and GlaxoSmithKline — supports the patent reform provisions outlined in the National Academy of Sciences’ (NAS) 2004 report, “A Patent System for the 21st Century.”

The report called for comprehensive changes to U.S. patent law to help mitigate the rising costs of acquiring and defending patents (DID, April 22, 2004). The recommendations included eliminating the best mode requirement and the inequitable conduct defense.

The ability to allege inequitable conduct on the part of the patent holder to argue that a patent is unenforceable results in excessive, expensive litigation, according to the coalition.

The coalition has also expressed disappointment that the current bill doesn’t repeal the best mode requirement. “Since inventors already must provide a full and exact description of how to make and use their inventions, this requirement does not add value for the public, but rather adds cost and unpredictability to patent lawsuits,” the group said.

The coalition recently joined other industry groups, including the Biotechnology Industry Organization (BIO), in sending a letter to congressional leaders expressing their concern with some parts of the bill, which they said would “fundamentally undermine patent certainty, discourage investment in innovative technologies and reduce publication and collaborative activities among academic scientists.”

The May 15 letter took issue with a provision that would limit damage awards in patent infringement suits. According to the bill, a court would have to consider the value of any prior art and deduct that value, so that the damages represent “the patent’s specific contribution over prior art.”

This would “devalue the contribution of many biotechnology patents,” BIO’s President and CEO Jim Greenwood said. “The right to fair compensation for infringement, and the right to fairly stop infringers from future infringing acts, are of paramount importance to the biotechnology industry and must be part of any legislation.”

Paul Michel, chief judge of the U.S. Court of Appeals for the Federal Circuit, also weighed in on the damages provision in a May 3 letter to Leahy and Hatch. Assessing the economic value of prior art is “a massive undertaking for which courts are ill-equipped,” he wrote.

The courts have recently played a major role in shaping patent policy, such as when the Supreme Court ruled that a patent licensee, MedImmune, did not have to terminate an agreement it made with Genentech in order to file for declaratory judgment (DID, Jan 10). GPhA commended the decision, saying it would remove obstacles to generic drug entry.

The administration has also shared its views on patent reform with members of Congress. In a May 16 letter to Berman, John Sullivan, general counsel of the Department of Commerce, wrote that the agency is in favor of revising the inequitable conduct defense, but that it believes the provision on damage awards is unnecessary.

The House Subcommittee on Courts, the Internet and Intellectual Property held two hearings on the bill in April, held a markup in May and forwarded the bill to the full Judiciary Committee.

The bill is available at thomas.loc.gov/cgi-bin/bdquery/z?d110:s.01145:. — Breda Lund


Study Finds Differences in FDA Review Times for Cancer, Alzheimer’s Drugs

The FDA approves HIV/AIDS and cancer treatments more quickly than treatments for other diseases such as Alzheimer’s, according to an analysis from Avalere Health.

While the agency met all of its mandated review timelines, cancer and HIV/AIDS treatments consistently exceeded the agency’s target goals and thus went to market more quickly than Alzheimer’s drugs, the study said. Eighty-eight percent of HIV/AIDS drugs received “priority reviews,” while 40 percent of Alzheimer’s treatments did, the analysis noted. Priority reviews last six months, while a standard review is 10 months.

In addition, 96 percent of HIV/AIDS treatments and 94 percent of selected cancer treatments received agency approval on the first cycle, while 60 percent of Alzheimer’s medications did. Approximately half of all FDA-reviewed products receive approval during the first cycle, which is consistent with the Alzheimer’s medications, the study found.

The analysis shows differences in the FDA’s review process and speed to market for Alzheimer’s products compared with other treatments, lead analysis author and Avalere Health Director Lauren Barnes said. She added that more research is necessary to understand the differences in reviews. Few Alzheimer’s treatments are currently on the market, so the sample size available to study is small, the analysis said.

The data came from product information from public and proprietary databases, Avalere said, adding that the analysis only looked at FDA review time for each product and did not consider the treatments’ clinical differences.

“This analysis shows that the federal government can make a positive difference in accelerating introduction of new medicines for the most daunting diseases Americans face,” Accelerate Cure/Treatments for Alzheimer’s Disease (ACT-AD) Coalition Chairman Daniel Perry said. ACT-AD, a group of nonprofit organizations, sponsored Avalere’s study. Wyeth also provided funding for the study.

Approximately 5 million people in the U.S. and 18 million people worldwide have Alzheimer’s, and the number is expected to grow, according to Avalere. — Emily Ethridge


HHS Buys 20 Million Doses of Smallpox Vaccine

HHS announced a contract for $500 million to Bavarian Nordic for 20 million doses of its modified vaccinia ankara (MVA) smallpox vaccine, Imvamune.

The total value of the deal is $1.6 billion, which includes funding for additional vaccine R&D, according to Bavarian Nordic. The contract also supports funding for clinical and nonclinical studies so the company can submit Imvamune to the FDA for review.

The vaccine will be added to the Strategic National Stockpile, HHS Secretary Mike Leavitt said, and would be used in the event of a smallpox outbreak to protect those with weakened immune systems.

The Strategic National Stockpile already contains enough smallpox vaccine courses for every U.S. citizen, but the vaccines were produced using vaccinia virus, a relative of smallpox virus. A live, replicating virus, vaccinia can cause side effects that can be potentially life-threatening, HHS said. People with compromised immune systems cannot receive that vaccine, but Imvamune contains a weakened form of the vaccinia virus that cannot replicate in humans, so it is safe.

This is the first Project BioShield contract awarded under the Pandemic and All-Hazards Preparedness Act of 2006, HHS noted. Under the act, the company can receive advance payments as it reaches certain milestones in product development, before the delivery of its product to the Strategic National Stockpile.

Under the contract, Bavarian Nordic will receive advance and milestone payments amounting to $150 million in 2007 and $125 million in 2008, the company said. The contract also includes an optional portion, worth $1.1 billion, to fund further clinical studies in children, elderly patients and patients infected with HIV, as well as funding for up to an additional 60 million doses of Imvamune.

“From the very first presentation of Imvamune for the U.S. government in 2001, we have had a constructive and trusting collaboration with the U.S. authorities,” Peter Wulff, president and CEO of Bavarian Nordic, said. “Therefore we do not consider this contract to be a single transaction, but rather the beginning of a long-term partnership with the U.S. government.” — Breda Lund


Industry-Funded Trials Biased Towards Sponsors’ Drugs, Study Says

Sponsors of clinical trials comparing two drugs head-to-head can affect which drug is deemed superior, according to a study analyzing 192 drug comparison clinical studies.

Clinical trials comparing statins with other drugs were more likely to report results and conclusions favoring the sponsor’s drug instead of the comparator drug, the analysis found. The study, conducted by three researchers at the University of California, San Francisco, and one from the University of Leiden, the Netherlands, was published in the June 7 edition of PloS Medicine.

Trials were approximately 20 times more likely to have results favoring the sponsor’s drug, and approximately 34 times more likely to have conclusions or interpretations favoring the sponsor’s drug, according to the study.

The study looked at results of 192 published randomized controlled trials from 1999-2005, involving seven different statins overall. Ninety-five of the trials were funded by industry, the study said, and approximately one-third did not disclose a funding source. The trials that did not disclose a funding source were less likely to have conclusions favoring the test drug, according to the analysis. 

There are several reasons why a trial could favor a sponsor’s drug, the researchers said. For example, drugmakers could only fund trials that are likely to produce a statistically significant result and could use nonequivalent doses of drugs for testing. In addition, sponsors could not report the results of studies that do not favor their drugs, the study noted.

Consumers need to be aware of the potential biases and financial conflicts of interests in comparison studies, the analysis noted. In particular, consumers choosing drugs for a formulary or insurance plan need to be skeptical of industry-funded comparison trials. 

Nearly half of the trials did not have adequate blinding in place to ensure the scientists did not know which drug patients were taking, according to the analysis. Studies with adequate blinding were less likely to report results favoring the sponsor’s drug, the study found. 

Industry group PhRMA criticized the study, saying it suggested the FDA did not regulate how companies used clinical trial results. Companies cannot use clinical trial information in marketing their products unless the FDA has approved it, and those who do not follow the agency’s rules will face enforcement action, PhRMA Senior Vice President Ken Johnson said. “It is simply not accurate to imply that the FDA would turn a blind eye to biased clinical trial data,” he added. 

The study can be seen at medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0040184. — Emily Ethridge


IRB Sanctioned for Continuing Violations

The St. Elizabeth Medical Center Institutional Review Board (IRB), Utica, N.Y., has been barred from allowing new subjects to be enrolled into ongoing clinical trials under its purview. Also, the FDA may withhold approval of any new studies the board has reviewed due to its repeated and continuing violations of its own written procedures and federal regulations, according to an FDA warning letter.

The IRB inappropriately approved clinical trials under an expedited review process and violated its own procedures by not holding meetings with the required frequency and allowing proxy voting, according to the May 8 warning letter, which was recently posted to the FDA website.

The IRB’s infringement of continuing review, expedited review, recordkeeping and written procedure requirements was repeated and continued since an April 2004 inspection that generated a November 2004 warning letter, according to the recent warning letter. Therefore, the agency will not lift its sanctions against the IRB until it receives evidence of adequate corrective actions.

The IRB inappropriately used expedited review, which is intended for “research involving no more than minimal risk or [to] review minor changes in previously approved research,” and in several instances, IRB members were notified of expedited review actions weeks or months after the fact, and not within one week as required, the warning letter said.

Moreover, the IRB secretary “was allowed expedited review authority to grant approval for significant study changes and annual renewal of significant risk studies,” although, being a nonscientific member of the board, this person may not have been qualified to act as a reviewer in all situations, especially those touching on medical concerns and risks to human subjects, the letter said.

The IRB membership roster has listed only 12 members since Oct. 12, 2005, one short of the full complement, the warning letter said. The IRB was also cited for:

  • Approving a clinical trial by proxy vote (e.g., mail-in paper ballots), even though no member is ever supposed to vote by proxy;
  • Meeting less than once every three months on four occasions since August 2004;
  • Not taking action against a member who attended only one IRB meeting out of nine since August 2004, although members are required to show up for at least half of all meetings;
  • Granting approval for use of a significant risk device for 16 months, instead of reviewing it after a year as required by regulations;
  • Failure to provide documentation of any action taken against a clinical investigator who submitted a required progress report two months late, and then only in rough draft form; and
  • Documentation failures, such as not maintaining copies of all research proposals and keeping inaccurate or incomplete meeting minutes.

IRB Secretary Martha Kodzy told DID that the warning letter contained “mostly administrative findings” and that the IRB has sent a response to the FDA.

The warning letter can be accessed at www.fda.gov/foi/warning_letters/s6359c.htm. — Martin Gidron

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