Drug Industry Daily - May 9, 2011 Issue

Vol. 10 No. 91

FDA Approves Novartis’ Afinitor for Pancreatic Tumors

The FDA has approved Novartis’ Afinitor (everolimus) for the treatment of advanced pancreatic neuroendocrine tumors (PNET), making it the first approval of treatment for this disease since Upjohn’s Zanosar (streptozocin) in 1982.

Afinitor is already approved to treat patients with renal cell carcinoma who previously failed other treatments, and to treat subependymal giant cell astrocytoma in patients for whom surgery is not an option. Afinitor’s new indication is for progressive PNET “in patients with unresectable, locally advanced or metastatic disease,” Novartis said Thursday.

The safety and efficacy of Afinitor was established in the RADIANT-3 trial that showed progression-free survival in patients treated with Afinitor was 11 months, versus 4.6 months in patients who received placebo, the FDA says.

During an April 12 meeting of the FDA’s Oncologic Drug Advisory Committee Meeting, committee members voted unanimously to support Afinitor’s approval, in part because of the “unmet need” for additional PNET treatments. However, committee members did suggest patients with carcinoid tumors avoid the drug (DID, April 13).

The FDA determined that the safety and efficacy of Afinitor in patients with carcinoid tumors had not been established, Novartis says.

Novartis has submitted applications for the same indication to the European Medicines Agency and the Swiss Agency for Therapeutic Products, the company says.

PNET are slow-growing and rare, and it is estimated that there are fewer than 1,000 new cases every year in the United States, the FDA says.

Approximately 60 percent of PNET patients are diagnosed with an advanced form of the disease, which means the cancer has likely spread and is difficult to treat, Novartis says. The five-year survival rate for PNET patients with advanced disease is 27 percent.

Afinitor is associated with a variety of adverse events, the most common of which include stomatitis, rash, diarrhea, edema and headache.

“Patients with this cancer have few effective treatment options,” Richard Pazdur, director of CDER’s Office of Oncology Products, said. “Afinitor has demonstrated the ability to slow the growth and spread of neuroendocrine tumors of the pancreas.” — Kevin O’Rourke


Grassley: Make Drugmaker–Advocacy Group Financial Ties Transparent

Sen. Chuck Grassley, a strong advocate of increased transparency of drugmaker–physician relationships, is again calling on physician and disease advocacy groups to publicly disclose funding they receive from the pharmaceutical industry.

Starting in 2013, drugmakers must disclose any payment or transfer of value made to a physician under a provision of the Affordable Care Act passed last spring (DID, March, 31, 2010). Drug companies must tell HHS the amount and date of each payment as well as its nature.

But Grassley notes the Medicare Payment Advisory Commission (MedPAC) last week recommended the requirement be spread to patient advocacy organizations. Disclosing industry-physician ties has been an ongoing issue for MedPAC (DID, Oct. 13, 2008).

In letters sent Wednesday to 15 organizations including the American Heart Association and American Diabetes Association, Grassley recognizes the public posting of funding support. However, the senator states he’d like to see the purpose of that funding.

Grassley singles out 18 other groups, including the American Academy of Family Physicians, the American Medical Association, American Cancer Society and the American College of Surgeons, for posting no information on their websites about funding support.

“These organizations have a lot of influence over the way taxpayer dollars are spent,” Grassley said of the advocacy and professional organizations. “They work to sway the legislative debates in Congress and government agencies such as the Food and Drug Administration and the Centers for Medicare and Medicaid Services rely on guidance from the organizations in writing rules and regulations and determining how public dollars are spent.”

The senator has previously asked other groups such as the American Psychiatric Association to disclose such data (DID, July 15, 2008). An APA spokeswoman told DID at the time it was working on the request, but the organization is one that doesn’t list any such funding information on its website, according to Grassley.

In his letters, Grassley praises the National Alliance on Mental Illness for voluntarily disclosing details of its industry support after a 2009 report found drugmakers provided the majority of its donations.

A number of companies, including Cephalon and Merck, already disclose payments they make to physicians (DID, Feb. 3, 2010).

Grassley’s letter is available at grassley.senate.gov/news/Article.cfm?customel_dataPageID_1502=34350. — David Pittman


Jazz Drops Rekinla for Fibromyalgia Due to Additional Clinical Trials

Jazz Pharmaceuticals is abandoning Rekinla, under development to treat fibromyalgia, to avoid long and expensive clinical trials requested in an FDA complete response letter last year.

The company said it decided against proceeding with the additional clinical studies for Rekinla (sodium oxybate) for the fibromyalgia indication after an internal analysis of the cost, development time and likelihood of regulatory approval associated with further clinical development in its first-quarter earnings.

In October, the FDA issued a complete response letter, which requested additional clinical trials, more information on patient selection and revisions to the risk evaluation and mitigation strategy (DID, Oct. 12, 2010).

Jazz did not return a request for comment on what types of clinical trials the FDA requested, but CEO Bruce Cozadd called the decision a “disappointing outcome” and said the trials “would take years to complete, would require a significant investment and would not sufficiently reduce regulatory uncertainty,” during a Tuesday conference call.

Cozadd added the company still believes in Rekinla as a treatment option for fibromyalgia, but funding clinical work at this time would not be a good use of its resources, unless there is a significant change in the requirements for pre-approval clinical trials, or they are able to gain additional regulatory certainty.

Rekinla is already approved as a treatment for narcolepsy under the name Xyrem. Jazz’s net sales of the oral solution rose by 49 percent to $42.8 million in the first quarter compared to the prior-year period, the company reported. — Molly Cohen


CDER Updates Responding to Waiver Requests for Postmarket Safety Reporting

CDER has updated its postmarket safety reporting requirements to include examples of waiver requests that are granted and denied.

In its Manual of Policies and Procedures (MAPP), CDER outlines how it handles requests to waive certain postmarket safety reporting requirements for approved NDAs, BLAs and ANDAs.

Although the policy document was first introduced in late 1999, the agency updated it Friday. Examples of waivers CDER has routinely denied from companies include:

  • Discontinuing all postmarketing safety reporting for active applications;
  • Not submitting individual case safety reports (ICSRs) for serious adverse experiences or unlabeled adverse experiences; and
  • Submitting domestic ICSRs on the Council for International Organizations of Medical Sciences I form instead of FDA Form 3500A.

The FDA also listed four occasions in which drugmakers’ request for waivers are routinely granted by CDER:

  • Submitting a periodic safety update report in lieu of a periodic adverse (drug) experience report, with no proposed change in frequency of reporting;
  • Extending the 15-day time frame for the submission of expedited ICSRs (15-day “Alert reports”) from annual poison control center reports or medical examiner reports;
  • Electronically submitting non-expedited ICSRs on an ongoing, real-time basis, rather than in a single batch;
  • No longer submitting ICSRs for non-serious, labeled adverse experiences.

However, the FDA noted, the fourth request isn’t routinely granted for new molecular entities that have been approved for less than three years.

A consult’s report last year said the agency should better adhere to its polices for tracking and communicating the status of postmarketing requirements and commitments (DID, Nov. 11, 2010).

The updated document is available at www.fda.gov/downloads/AboutFDA/CentersOffices/CDER/ManualofPoliciesProcedures/UCM079937.pdf. —David Pittman


Jury Still Out on Cost-Effectiveness of IT in Medication Management

Despite high acquisition and implementation costs, medication management information technology (MMIT) offers the potential for improved processes and outcomes, but more economic and clinical research is needed to determine cost-effectiveness, a report by the Agency for Healthcare Research and Quality (AHRQ) concludes.

Only five of 31 economic articles reviewed for AHRQ were full economic evaluations with information on the incremental costs and effects associated with MMIT. The majority (84 percent) involved more limited cost analyses.

“The effectiveness of any given system is dependent on the system’s design, implementation, the users of the system, and the setting into which the system is being introduced. Adoption of newer technologies needs to be based on formal evaluation of whether the additional health benefit (effectiveness) is worth the additional cost,” the report says.

It adds: “Given the tension between the clinical benefits of integrated [computerized provider order entry] and [clinical decision support systems (CDSS)] systems and the high upfront costs, decisionmakers deciding whether to implement them need to better understand how and when financial benefits of such systems accrue (e.g., short-term compared with long-term benefits).”

Likewise, the report found inconclusive evidence on the impact of MMIT on clinical outcomes.

Of 76 articles that assessed clinical outcome, slightly more than half (54 percent) reported significant benefits, the report says. Studies that monitored patients with specific conditions or care needs in order to identify problems and intervene were generally more effective than CDSS interventions that focus on theoretical issues, such as the potential for adverse drug effects, the report says.

Studies with successful outcomes also tended to target high-risk patient populations with poor disease control, limited healthcare access or subgroups who had the financial wherewithal to respond to the CDSS approach.

However, critically ill patients are also more likely to be harmed, or even die, as the result of poorly performing technology and implementation strategies, which can cause delays in treatment, the report says.

The aim of the report was to review the evidence on health IT’s impact on all phases of the medical management process — prescribing and ordering, order communication, dispensing, administration, monitoring and education and reconciliation.

According to the report, U.S. prescription drug costs were about $246.3 billion in 2010. Use of MMIT has the potential for increased efficiencies in drug prescribing, control and recordkeeping.

The report includes data from 428 articles on seven key questions:

  • Effectiveness;
  • Gaps in knowledge or evidence;
  • Value proposition for implementers and users;
  • System characteristics;
  • Sustainability;
  • Two-way prescription electronic data interchange; and
  • Randomized controlled trials of CDSS.

Studies of prescribing and monitoring outnumbered studies on economic and clinical outcomes, and they also tended to use stronger comparative methods, the report says.

MMIT was associated with improvements in prescribing in 87 percent of hospital-based studies, compared with 68 percent in ambulatory-based studies. Sixty-eight percent of hospital-based studies also showed a decline in prescription and ordering errors, while errors were rarely studied in ambulatory settings.

MMIT also resulted in better adherence to treatment guidelines, reminders and recommended practice in hospitals (83 percent, 19 of 23 studies) and ambulatory care (64 percent, nine of 14 studies), AHRQ found.

The report, “Enabling Medication Management Through Health Information Technology (Health IT),” is available at www.ahrq.gov/downloads/pub/evidence/pdf/healthit/medmgt.pdf. — Meg Bryant

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Reporters: Virgil Dickson, Molly Cohen, David Pittman, Kevin O'Rourke, Sarah Karlin

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