DID - Nov. 19, 2009 Issue

Vol. 8. No. 226

Senate Healthcare Bill Preserves Biologics Exclusivity, Drugmaker Fees

The Senate’s $849 billion healthcare overhaul legislation, like the House version, gives biologics innovators 12 years of exclusivity and requires a 50 percent discount on negotiated prices for brand drugs in Medicare formularies when beneficiaries fall into a coverage gap, but unlike the House bill, it would charge brand-drug makers $2.3 billion in annual fees.

The Patient Protection and Affordable Care Act, H.R. 3590, released Wednesday evening, must get 60 votes to open debate on it before the full Senate votes whether to approve it. If the full Senate approves it, the bill then must be reconciled with the House version, The Affordable Health Care for America Act, H.R. 3962 (DID, Nov. 9).

The reconciliation of the two bills could prove difficult because they do not share important provisions. For example, the House bill would allow the government to negotiate prices for Medicare Part D drugs directly with pharmaceutical companies (Section 1181 of the bill) and would ban pay-for-delay agreements between brand-drug and generic-drug makers (Section 2573). The Senate version does not include either provision, but it includes $2.3 billion in annual fees the industry agreed to pay (Section 9008) (DID, Sept. 10).

Both bills contain a provision to reduce the Medicare Part D coverage gap, which is expected to cost the drug industry $80 billion over 10 years (DID, June 23). They both also would allow Medicare Advantage prescription drug plans to waive copayments for first fills of generic prescription drugs as an incentive for beneficiaries to try less expensive formulations (Section 6402 in the Senate bill).

Both bills also contain provisions to fund comparative-effectiveness research. The Senate legislation would create a nonprofit Patient-Centered Outcomes Research Institute to study comparative-effectiveness research, including the health outcomes, clinical effectiveness, and appropriateness of medical treatments and services, the bill says in Section 6302.

The two bills also contain provisions that effectively would expand discounts from drugs purchased through the 340B Drug Discount Program by including drugs bought by children’s hospitals and cancer hospitals among other institutions (DID, Oct. 8). The minimum rebate percentage for single-source and innovator multiple-source drugs covered under Medicaid would be set at 23.1 percent under the Senate bill (Section 2501) — the House version sets the minimum at 22.1 percent (Section 1742) — and sets 13 percent as the minimum for other drugs.

The Congressional Budget Office and the Joint Committee on Taxation released a preliminary analysis of the bill Wednesday, which estimates that the legislation would result in a net reduction in federal budget deficits of $130 billion from 2010 to 2019.

The Patient Protection and Affordable Care Act can be found at www.democrats.senate.gov/reform/patient-protection-affordable-care-act.pdf. H.R. 3962 is available at www.fdanews.com/ext/files/HR3962PatientProtection.pdf. — David Belian


OIG Finds Flaws in NIH Oversight of Conflicts of Interest

Institutions and researchers given NIH grants could be subject to new rules for increased transparency and oversight of potential financial conflicts of interest, as recommended by an HHS Office of Inspector General (OIG) report.

Ninety percent of institutions that receive NIH funds allow researchers to decide which significant financial interests are related to their research and must be reported, the OIG report, released Wednesday, says. The same institutions rarely reduce or eliminate the conflicts of interest, the report adds.

The OIG report recommends that NIH require institutions to collect information on all significant financial interests and not just those that researchers decide are applicable, and develop guidance on verifying researchers’ financial interests. It also suggests NIH regularly request details from grantees on how they are managing, reducing or eliminating conflicts of interest.

The report follows closely on the heels of other public and private actions calling for greater transparency in researchers’ financial affiliations. It was released soon after a group of 100 researchers asked NIH to finance studies on conflicts of interest in medicine and research (DID, Nov. 18). It also comes a day after Sen. Chuck Grassley (R-Iowa) wrote to 10 academic institutions asking for their policies on ghostwriting (DID, Nov. 19).

The most common type of financial conflict of interest among NIH-funded researchers is equity ownership in companies, the report says. Grantee institutions frequently disclose these conflicts in publications or presentations as a way to mitigate them, the report adds.

The OIG recommends that NIH’s stricter oversight include requesting that institutions provide specific amounts of equity and compensation and how the financial conflicts are managed, reduced or eliminated.

The OIG report found that:

  • Institutions receiving NIH grants are not required to report any financial interests they have with outside companies;
  • Conflicts were not uniformly reported by institutions;
  • Most of the grantee institutions do not have policies to address compliance with federal conflict regulations in individuals or groups who receive part of the grant;
  • Institutions lack documentation to support their oversight of conflicts;
  • The specific financial interests of researchers are often unknown; and
  • Grantee institutions do not routinely verify information submitted by researchers.

The NIH reply included in the report says the institutes would consider developing the verification guidance but that their ability to make regular requests for details of grantees’ management could require a new rule.

The OIG says the current regulation does not prohibit NIH from requesting follow-up information from grantee institutions on reported conflicts. It also advises that, where necessary, NIH amend its regulations to enhance its oversight. The OIG requests that NIH’s final management decision indicate whether it concurs with the recommendations overall and what steps, it any, it will take to implement them.

The NIH also noted that many of the OIG’s observations are addressed in a recent advanced notice of proposed rulemaking to be considered by NIH and HHS (DID, May 18).

The OIG report, “How Grantees Manage Financial Conflicts of Interest in Research Funded by the National Institutes of Health,” is available at oig.hhs.gov/oei/reports/oei-03-07-00700.pdf. — April Hollis


FDA Issues Complete Response for Use of Rituxan for Leukemia

The FDA has sent Genentech and Biogen Idec a complete response letter about their applications to use Rituxan plus chemotherapy for patients with untreated chronic lymphocytic leukemia (CLL).

The companies will continue to discuss labeling with the FDA for the new indications, which include previously treated patients, according to the companies’ statement Nov. 18.  Rituxan (rituximab) is approved for CLL in Europe under the brand name MabThera. The product is a therapeutic antibody that binds to a protein called CD20 on the surface of cancerous and normal B-cells, helping the immune system eliminate CD20-positive B-cells.

The FDA based its decision on two trials comparing Rituxan in combination with fludarabine and cyclophosphamide and chemotherapy alone (DID, Dec. 9, 2008). The CLL8 study enrolled 817 patients at 191 sites in 11 countries. Sponsored by Roche, which owns Genentech, the study showed that after two years, 76.6 percent of previously untreated patients given Rituxan and chemotherapy survived without further advance of their disease, compared with 63.3 percent of those receiving chemotherapy alone.

In the REACH study sponsored by Genentech and Biogen Idec, patients who had relapsed and were given Rituxan plus chemotherapy lived an average of 10 months longer without further disease progression than patients getting chemotherapy only (30.6 months versus 20.6 months). That study involved 552 patients at 88 sites in 17 countries.

Rituxan was discovered by Biogen Idec and first approved by the FDA in November 1997 for the treatment of relapsed or refractory, low-grade or follicular, CD20-positive, B-cell non-Hodgkin’s lymphoma. It is co-distributed in the U.S. by Genentech and Biogen.

In February 2006, the FDA approved Rituxan in combination with methotrexate for the treatment of adults with moderate-to-severe rheumatoid arthritis who did not respond to one or more tumor necrosis factor antagonist therapies. Genentech reported net U.S. sales of Rituxan of $2.6 billion in 2008, and Biogen reported $1.1 billion in sales of the drug, according to the companies’ annual reports. — Meg Bryant


FDA Warns 22 Internet Pharmacies About Illegal Drugs

Internet sites that sell pharmaceuticals to U.S. consumers received a strong warning as the FDA sent warning letters to 22 website operators selling drugs illegally.

The FDA’s Office of Criminal Investigations (OCI), CDER, Office of Regulatory Affairs and Office of Enforcement focused on 136 websites allegedly selling unapproved or misbranded drugs to U.S. consumers, the FDA says in a statement Thursday.

“These drugs are often counterfeit, contaminated or unapproved products, or contain an inconsistent amount of the active ingredient,” FDA Commissioner Margaret Hamburg says in the statement. The FDA notes none of the sites are run by pharmacies in the U.S. or Canada.

The enforcement effort, called the International Internet Week of Action (IIWA), is sponsored by the World Health Organization’s International Medical Products Anti-Counterfeiting Task Force, International Criminal Police Organization, Permanent Forum on International Pharmaceutical Crime, and health and law enforcement agencies from 26 countries, the statement says.

The IIWA’s goal is to protect public health by increasing public awareness of the dangers of purchasing medical products online, identifying producers and distributors of counterfeit medical products, seizing violative products to remove them from the supply chain, and targeting individuals and businesses with civil or criminal action.

As part of its effort, the FDA also notified internet service providers and domain name registrars that the sites were selling products in violation of U.S. law. In many cases, these violations give service providers and registrars grounds to terminate the websites and suspend the use of the domain names, the agency says.

FDA import specialists, with OCI and several other U.S. government agencies, are targeting violative drug products moving through certain international mail facilities and express courier hubs, the statement says.

The warning letters, which cite violations such as selling unapproved and misbranded drugs, were sent to:

  • Andrey Petroff;
  • Antonio Mendez;
  • Buzz;
  • Chen-Yu Ou;
  • Chris Walsh;
  • D Hunter;
  • Eugene Lefter;
  • Forrest Media;
  • Krest Holdings;
  • Lorna Hillier;
  • Med Light;
  • New Horizons;
  • Onlinepharmacyy.com@proxy.dreamhost.com;
  • Orion Star & Associates;
  • Panama SA;
  • Pro West Marketing;
  • Randek I-warez;
  • Ric Deleon;
  • Sinan Akyuz, who received two letters;
  • Tvforever;
  • William Wynne; and
  • Xanos Holdings.

Despite a lack of guidelines specifically for internet promotions, the FDA’s Division of Drug Marketing, Advertising and Communications has devoted increased staff and resources to internet monitoring and enforcement over the past year (DID, Sept. 23).

Pro West Marketing, Chris Walsh and Ric Deleon, three of the warning letter recipients, did not respond to a request for comment by press time. Many of the other websites already are shut down. The warning letters can be seen at www.fda.gov/ICECI/EnforcementActions/WarningLetters/2009/default.htm. — April Hollis


Zavesca Given Priority Review for Niemann-Pick Disease

The FDA is slated to begin reviewing Actelion’s supplemental NDA (sNDA) for Zavesca to treat progressive neurological manifestations in adults and children with Niemann-Pick type C disease (NP-C) early next year.

Zavesca (miglustat) is indicated for oral treatment of adults with mild-to-moderate Type 1 Gaucher’s disease when enzyme replacement therapy is not an option, the company says in a statement Thursday. The Endocrinologic and Metabolic Drugs Advisory Committee is scheduled to consider the sNDA Jan. 12, 2010.

Actelion based its sNDA on a clinical trial, OGT 918-007, and two multicenter retrospective cohort studies in patients with NP-C, the company says.

“Miglustat could become the first treatment for NP-C in the USA,” Jean-Paul Clozel, CEO of the Swiss company, says in a release.

The FDA granted miglustat for NP-C orphan status in 2008. Zavesca accounted for $37.8 million in worldwide sales in the first nine months of 2009, according to the company’s earnings report. — Meg Bryant


AstraZeneca Files NDA for Acute Coronary Syndrome Drug

AstraZeneca is seeking FDA approval for its Brilinta treatment to reduce heart attacks and other adverse cardiac events in patients with acute coronary syndrome.

Brilinta (ticagrelor), an oral antiplatelet treatment, has not received a Prescription Drug User Fee Act review date, Neil McCrae, a spokesman for AstraZeneca, told DID Thursday.

AstraZeneca submitted the results from a Phase III head-to-head trial in support of the NDA. The trial compared Brilinta plus aspirin with Sanofi-Aventis and Bristol-Myers Squibb’s (BMS) anti-blood-clotting drug Plavix (clopidogrel bisulfate) plus aspirin, the company says in a statement.

If approved, Brilinta would be the first reversibly binding oral P2Y12 adenosine diphosphate (ADP) receptor antagonist, AstraZeneca says. ADP receptor antagonists help prevent platelets from sticking together, reducing recurrent thrombotic events.

The drug would face competition from Plavix, which had worldwide sales of $9.4 billion in 2008, according to BMS’ and Sanofi’s SEC filings. — David Belian

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