DID - Dec. 21, 2009 Issue

Vol. 8 No. 246

AAHRPP Lengthens Reaccreditations, Tightens Compliance Policies

The Association for the Accreditation of Human Research Protection Programs (AAHRPP) is extending its reaccreditation period for drug sponsors and IRBs while tightening some of its other compliance policies.

AAHRPP’s board of directors voted last week to lengthen the current reaccreditation period from three years to five, beginning Jan. 1, to improve efficiency for members and the association itself. However, the initial accreditation period will remain at three years.

“We want to reduce the burden on organizations, so they can spend more time doing what they have to do in order to remain accredited,” AAHRPP spokesman David Ward told DID Friday.

The directors also voted to approve the use of status reports and limited site visits to resolve noncompliance issues between annual reports, Ward said. Under the new policy, the directors can ask members for status updates at any time and request site visits to verify compliance.

“This isn’t meant to be punitive in any way,” Ward said, adding that the new policies will help AAHRPP address compliance issues more efficiently.

Another new policy calls for more specific information in annual reports. Starting in January, annual reports must include information about catastrophic events and changes in a member’s organization, resources, program scope and program delivery, according to the association.

Previously, the reports contained general information, such as a summary or table of major problems or deficiencies identified in the past year and their resolution, Ward said.

The association revised its accreditation standards for the first time in October, adding new standards for transnational research and conflicts of interest. It also added or tightened standards on community-based research and data and safety monitoring (DID, Oct. 1).

The group accredits large research institutions, institutional review boards and industry sponsors with in-house research programs. It recently accredited its 200th member.

“We’re very happy with the 200,” Ward said. “I think as we get more of a critical mass, then more organizations will probably want to join.” — Owen Skoler


Report: CDC Advisory Committees Not Vetted for Conflicts of Interest

The U.S. Centers for Disease Control and Prevention (CDC) failed to adequately oversee the ethics program for members of committees like the one that recommended routine vaccination with Merck’s Gardasil to prevent cervical cancer, a report says.

The CDC failed to identify or resolve conflicts of interest for 64 percent of special government employees (SGE) who sat on its advisory committees in 2007, according to an HHS Office of Inspector General (OIG) report issued Friday. Some SGEs didn’t report stock ownership in companies whose products they reviewed or failed to acknowledge that they received consulting fees, honoraria or speaking fees from the companies, the report says.

Such unresolved conflicts could compromise the integrity of the committees’ work, the report says, adding that CDC committees have made recommendations for several top-selling drugs in recent years, including the influenza A (H1N1) vaccine.

The CDC agreed with the report’s recommendations — such as ensuring SGEs’ confidential financial disclosure reports are complete before certifying them and identifying and resolving SGE conflicts of interest before permitting the employees to participate in committees — and has begun implementing them, it says in a response to the report.

Vetting advisory committee members can be a resource-intensive task for government agencies. CDER policy, for example, requires that most new medical entity NDAs and original BLAs be discussed by advisory committees, whose increased use is creating a strain on FDA resources, according to John Jenkins, director of the FDA’s Office of New Drugs.

The number of FDA advisory committee meetings increased to 43 in fiscal 2009 from 27 in fiscal 2008 and the number of advisors screened for potential conflicts of interest increased to 875 from 489. The number of advisors cleared also increased to 663 from 380. Impaneling committees with appropriate experts without significant conflicts of interest is difficult, according to Jenkins (DID, Dec. 11).

Bringing such conflicts to light is also a priority for Congress. Transparency provisions are in both the House and Senate healthcare overhaul bills, as section 1451 in the House’s Affordable Healthcare for America Act (H.R. 3962) and as section 6002 of the Senate’s Patient Protection and Affordable Care Act (H.R. 3590).

The FDA and CDC declined to comment on the OIG report Friday.

The OIG report, “CDC’s Ethics Programs for Special Government Employees on Federal Advisory Committees,” can be found at oig.hhs.gov/oei/reports/oei-04-07-00260.pdf. — David Belian


Spiriva Wins Expanded Indication for COPD

The FDA has approved a new indication for Boehringer Ingelheim’s Spiriva HandiHaler to reduce exacerbations of chronic obstructive pulmonary disease (COPD).

Spiriva (tiotropium bromide monohydrate) inhalation powder is the first nonsteroid maintenance therapy shown to reduce worsening of COPD, the company said Friday. The new indication was supported by two clinical trials, one lasting six months and one long-term study.

The inhaled drug has approval for long-term, once-daily maintenance treatment of bronchospasm associated with COPD and is marketed with Pfizer, Boehringer said.

Boehringer reported 2008 global Spiriva sales of about $3 billion in its annual report. — Meg Bryant


US PTO Upholds Merck’s Patent on Singulair

The U.S. PTO, which upheld Merck’s patent on its Singulair asthma and allergy drug, will send the drugmaker a certificate of reexamination within two to three months.

The certificate “essentially grants our claims,” Ron Rogers, a spokesman for Merck, told DID Friday. The PTO has “now said that they agree with our arguments, they’ve issued their response indicating they’re going to terminate the reexamination at this time, and the procedural step is to issue this grant of certificate.”

The patent office withdrew an earlier ruling that the ’473 patent on Singulair (montelukast sodium) was not valid due in part to a doctor’s declaration submitted to show the process involved in the patent would not have been obvious to someone “of ordinary skill,” the office says.

The PTO decided to reexamine the patent covering Singulair in August as a result of an investigation by Article One Partners, which looks for evidence that can legitimize or invalidate selected patents, according to the global online group’s website (DID, June 1).

The decision by the PTO to uphold the patent follows a ruling from the U.S. District Court for the District of New Jersey in August that Teva Pharmaceuticals USA had infringed Merck’s patent by filing an ANDA for a generic version of Singulair (DID, Aug. 20).

The court rejected Teva’s argument that the ’473 patent, which has pediatric exclusivity until Aug. 3, 2012, is obvious in light of prior art, saying the drugmaker hadn’t provided “clear and convincing evidence,” according to court documents.

The Singulair franchise had worldwide sales of about $2.32 billion during the first half of the year, according to a Merck financial statement. — David Belian


New Verelan PM Label Calls Attention to Interactions

The FDA has approved labeling revisions to Elan’s hypertension drug Verelan PM that add the drug’s interactions with clonidine, a treatment for high blood pressure, and telithromycin, a drug to treat certain types of pneumonia caused by bacteria.

The FDA has required labeling changes for Verelan PM (verapamil HCl) and all drugs containing that active ingredient to include the interaction with clonidine, Carl Bauman, director of product safety and labeling for Elan, told DID.

Sinus bradycardia resulting in hospitalization and pacemaker insertion has been reported in association with concurrent use of clonidine and verapamil, the new label says. It suggests physicians monitor the heart rate of patients receiving both drugs.

Hypotension and bradyarrhythmias also have been observed in patients receiving both telethromycin and verapamil, the new label says.

Elan submitted revisions to the drug’s label before the FDA’s requirement to include interactions between verapamil and clonidine, Bauman said, adding that the inclusion of the interaction was coincidental.

Revenue from Verelan was $16.9 million for the first three quarters of 2009, according to Elan’s third-quarter financial report. — Owen Skoler


Amgen’s Bone-Loss Drug Prolia Gets CHMP Nod

The European Medicine Agency’s (EMEA) Committee for Medicinal Products for Human Use (CHMP) recommended approval of Amgen’s human monoclonal antibody drug Prolia to treat postmenopausal osteoporosis in women and male bone loss associated with hormone ablation treatment for prostate cancer.

Prolia (denosumab) is a first-in-kind drug designed to block proteins that trigger bone-destroying cells. Initial indications are for 60 mg/mL injections, administered twice yearly, in adults at risk of fractures due to treatment-related hormone loss, CHMP said Friday.

The drug has the ability to significantly reduce the risk of vertebral, hip and nonvertebral fractures and increase bone mineral density in postmenopausal women and men with prostate cancer, the committee said.

Positive opinions on marketing authorizations by CHMP are generally green-lighted by the EMEA within several months, meaning the drug could reach the European market by early next year. The drug will compete in the osteoporosis market with a class of drugs called bisphosphonates, including Merck’s Fosamax (alendronate sodium), Procter & Gamble’s Actonel (risedronate sodium), GlaxoSmithKline’s (GSK) Boniva (ibandronate sodium) and Novartis’ Zometa (zoledronic acid).

CHMP based its opinion on six Phase III clinical trials, including two pivotal studies, according to Amgen. Common side effects from the drug include urinary tract infection, upper respiratory tract infection, cataract, constipation, rash, sciatica and arm and leg pain, CHMP said.

Under a July agreement, Amgen will market the drug jointly in the EU with GSK. The arrangement also gives GSK a share in commercializing the drug in Australia, New Zealand and Mexico, and control of sales in emerging markets such as China, India and South Korea where Amgen does not have a presence. Amgen retains full rights to Prolia in the U.S. and Canada and for potential cancer indications in Europe.

Amgen also has a deal with Daiichi Sankyo aimed at developing and commercializing denosumab in Japan (DID, July 16, 2007).

Prolia is still awaiting a go-ahead from the FDA, which has requested additional information on Amgen’s postmarket monitoring plan for the drug (DID, Oct. 20). — Meg Bryant

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