Washington Editor

WASHINGTON - The National Institute of Allergy and Infectious Diseases (NIAID) has scrapped a large-scale HIV vaccine study, known as PAVE 100, and has opted instead to conduct a smaller, more focused trial of the agency's investigational vaccine.

PAVE 100, which planned to enroll 8,500 volunteers in the U.S., South America, the Caribbean and Africa, was set originally to begin last October but was postponed after a Phase IIb study testing Merck & Co.'s MRKAd5 trivalent was halted because it could not be shown to prevent HIV infection or affect the course of the disease in infected patients.

Later analyses of the multinational, multisite 3,000-patient Merck trial, known as STEP, found increased numbers of HIV infections among those volunteers who received the vaccine.

The highest risk of HIV infection among vaccinated volunteers in STEP appeared to be among men who were uncircumcised and had preexisting neutralizing antibodies to adenovirus type 5 (Ad5), the cold virus used in the vaccine as a carrier for the HIV genes.

After the Merck vaccine failure, NIAID had redesigned PAVE 100 to include only 2,400 U.S.-based, circumcised men who have sex with men and who lack preexisting neutralizing antibodies to Ad5.

The revised study would have tested the vaccine's effect on viral load, provided additional safety information about the product and examined in detail immune responses to the vaccine and their impact on viral load.

But after receiving input from the scientific and HIV advocacy communities, the agency said it determined that its vaccine regimen did not warrant a large trial and decided to move forward instead with a leaner, more focused trial, for which it has yet to provide details.

NIAID hosted a public meeting of HIV/AIDS experts in March to determine a path forward for its trial and research and spending for HIV infection. At that meeting, NIAID Director Anthony Fauci said his agency planned to make adjustments to its vaccine research efforts, including shifting more of its funding to laboratory rather than clinical research activities. (See BioWorld Today, March 26, 2008.)

"An HIV vaccine continues to be our best hope for ending the HIV pandemic," NIAID officials said in a statement.

Seth Berkley, CEO of the International AIDS Vaccine Initiative, called NIAID's decision to abandon the PAVE 100 trial design "bold," stating that it "bears in mind the lessons offered by the STEP study."

"That is the way good scientific endeavors work," Berkley said in a statement. "The decision by NIAID does not reflect paralysis in the AIDS vaccine field or a lack of direction forward. In fact, it reflects the opposite. It reflects the dynamic learning that is the scientific process that is pharmaceutical product development."

In the wake of STEP, he said, smaller studies "should become the norm to test for a sign of promise before proceeding to large efficacy trials."

Washington Strongman to Advise Insmed

Former California lawmaker Bill Thomas, who chaired the powerful House Ways and Means Committee from 2001 to 2007, has hooked up with Richmond, Va.-based Insmed Inc. to help the firm navigate Washington and the brewing follow-on biologics (FOBs) legislation.

Thomas, a Republican member of the House for 28 years before retiring in 2007, was known in Washington during his tenure as a workhorse. He played a strategic role in getting the Medicare Prescription Drug, Improvement and Modernization Act of 2003 passed. In addition, Thomas claimed he was instrumental in laying the groundwork for the FOBs debate.

Insmed CEO Geoffrey Allan said the former lawmaker is someone who "knows the arguments inside out on both sides of the table."

"Mr. Thomas is a very passionate believer in the need for follow-on biologics," he told BioWorld Today. "He's obviously been around the scene for quite sometime, and he recognizes the need to break down these monopolies and to allow these products to be manufactured and provided to consumers at a fairly cheaper price."

Allan said his firm was not actively searching for a Washington insider to "shake the corridors of power." Rather, he said he met Thomas at a Washington function hosted by the conservative think tank the American Enterprise Institute, where the former California congressman is a fellow. "We caught his attention by being able to demonstrate that we knew what we were doing," Allan said, noting that his firm is developing INS-19, a recombinant human granulocyte colony stimulating factor (G-CSF), to treat neutropenia.

The compound is a FOBs version of Thousand Oaks, Calif.-based Amgen Inc.'s Neupogen (filgrastim), which had 2007 sales of about $1 billion. Insmed earlier this month reported that INS-19 demonstrated bioequivalence to Neupogen in a randomized, double-blind Phase I trial.

"We showed perfect bioequivalence," Allan said. "The data were just extremely pristine."

The company claimed to be the first U.S. firm to report human bioequivalence data for a follow-on biologic product.

The firm plans to seek permission from the FDA to begin a Phase III trial of INS-19.

Allan said that Thomas was attracted to his company's success with INS-19 and the fact that has successfully gained FDA approval of a biologic product, Iplex, a complex of recombinant human insulin-like growth factor and its predominant binding protein IGFBP-3.

The drug was approved in 2005 for the treatment of children with growth failure due to severe primary IGF-I deficiency. It also is being investigated in myotonic muscular dystrophy and amyotrophic lateral sclerosis.

Insmed's successful approval of Iplex and its pioneering work in FOBs has made Thomas an advocate for the firm and willing to "fight the fight that deserves to be fought" for enactment of legislation that would create a pathway for approval of FOBs, Allan said.

Published  July 21, 2008