DID - Nov. 6, 2009 Issue

Vol. 8 No. 217

Republican Healthcare Bill Contains 12-Year Biologic Exclusivity Period

Manufacturers of brand biologics would receive a 12-year exclusivity period under healthcare overhaul legislation proposed by House Republicans.

The legislation’s exclusivity provision is for the same length of time as in the Affordable Health Care for America Act, H.R. 3962, which was proposed by House Democrats last week. It also is for the same length of time as the period in the Affordable Health Choices Act passed by the Senate Health, Education, Labor and Pensions (HELP) Committee in July (DID, July 15).

Unlike the House Democrats’ bill, however, the Republican bill does not have language that would enable innovator and generic biologics to be billed with the same payment code to Medicare and Medicaid.

The 12-year exclusivity period has met with resistance from the Generic Pharmaceutical Association (GPhA), which asked President Barack Obama to tell Congress to strike the language from healthcare overhaul legislation in a letter sent last week (DID, Oct. 29).

“An unprecedented exclusivity period would skew investment away from biogenerics and, thus, severely diminish the prospects for creating a robust biogeneric industry capable of injecting the competition needed to achieve optimal cost savings,” Kathleen Jaeger, GPhA president and CEO, says in the letter.

Innovator groups, such as the Biotechnology Industry Organization (BIO), have praised the 12-year exclusivity period. The time period “strikes the appropriate balance among ensuring patient safety, expanding competition, reducing costs and providing necessary and fair incentives that will provide for continued biomedical breakthroughs,” BIO President and CEO Jim Greenwood says in a statement following the Senate HELP Committee’s inclusion of the provision.

The Republican measure, which could be offered to the full House soon as a substitute for H.R. 3692, can be found at www.fdanews.com/ext/files/RepublicanAlternative3962_9.pdf. — David Belian


Prempro Court Cases Are Going Against the Drugmaker

A Philadelphia jury ruled against Pfizer in a lawsuit by a woman who claims that the hormone treatment Prempro, developed by the company’s Wyeth subsidiary, gave her breast cancer in the latest decision in a lawsuit over the drug’s alleged cancer risks.

The Court of Common Pleas in the First Judicial Circuit of Pennsylvania has sealed the amount of punitive damages the jury determined last week in Barton v. Wyeth Pharmaceuticals Inc., et al. until a final verdict is reached in another case the court is scheduled to hear, Kendall v. Wyeth, which also involves Prempro (conjugated estrogens/medroxyprogesterone acetate). Punitive damages in Barton v. Wyeth reportedly total $75 million.

When the second case is decided, a sealed verdict in a third case, Daniel v. Wyeth, also will be released.

“The company believes there is no basis in fact or law for the jury’s verdict in the Barton case,” Wyeth spokesman Christopher Loder told DID. “We plan to ask the judge to reject the compensatory and punitive awards. We anticipate that if the judge does not grant judgment notwithstanding the verdict, we will appeal.”

One of the law firms representing the plaintiff in Barton v. Wyeth, Janet, Jenner & Suggs, declined to comment.

In a separate Prempro case decided this week, the U.S. Court of Appeals for the Eighth Circuit upheld a jury verdict in Donna Scroggin v. Wyeth, et al. awarding Scroggin $2.7 million in compensatory damages for the breast cancer she developed after taking Prempro (DID, March 11, 2008).

However, the appeals court vacated the more than $27 million in punitive damages the jury levied against Wyeth and Pharmacia & Upjohn, a separate Pfizer unit that makes Provera (medroxyprogesterone acetate), one of the components of Prempro.

The court remanded the case to the U.S. District Court for the Eastern District of Arkansas for a new trial to determine the punitive damages. — Martin Berman-Gorvine


Abraxane Gets Recalled in UK, Orphan Status in US

Abraxis BioScience is recalling a batch of chemotherapy agent Abraxane in the UK after finding particulate matter in other batches made at the same time.

The precautionary recall of 5-mg/mL Abraxane (paclitaxel), an injectable suspension of protein-bound particles, is expected to create a shortage through the first quarter of 2010, the Medicines and Healthcare products Regulatory Agency says in a Thursday statement.

The company has not received reports of unusual or unexpected adverse reactions with affected lots, a company spokeswoman told DID. She could not comment on the root cause of the contamination.

The Class II recall comes as Abraxis received orphan drug status in the U.S. for the product, according to a company statement Thursday. It was approved by the FDA in 2005 to treat breast cancer after failure of combination chemotherapy for metastatic disease or relapse within six months of adjuvant chemotherapy, the statement says. The drug is in development to treat pancreatic cancer and stage IIB-IV melanoma.

Additionally, enrollment is ongoing in two Phase III studies:

  • Abraxane plus gemcitabine, versus gemcitabine alone, as a first-line therapy for advanced metastatic pancreatic cancer; and
  • Abraxane compared with dacarbazine to treat stage IV chemotherapy-naive melanoma patients.

Abraxis also is continuing to study the drug in a variety of tumor types, it says.

In 2006, the FDA warned Abraxis for distributing pharmaceuticals that could have been contaminated during manufacture as a result of several good manufacturing practice deviations (DID, Feb. 20, 2007). — April Hollis


Amgen’s Vectibix Misses Overall Survival Endpoint in Colorectal Cancer

Amgen’s Vectibix failed to improve overall survival in a Phase III clinical trial evaluating it as a first-line treatment in metastatic colorectal cancer, according to the company.

Overall survival was a secondary endpoint in the study, Amgen says in a statement Thursday. The company had earlier announced that the drug met the primary endpoint of significantly prolonging progression-free survival.

The trial evaluated Vectibix (panitumumab) in combination with Folfox, an oxaliplatin-based chemotherapy. Many of the 1,183 patients enrolled in the trial had the KRAS mutation.

Median overall survival was 23.9 months for those on the drug plus Folfox compared with 19.7 months for patients treated with Folfox alone. The median overall survival difference of 4.2 months in the Vectibix arm was not statistically significant, but Roger Perlmutter, Amgen’s executive vice president of R&D, said it is nevertheless encouraging.

Vectibix is approved to treat metastatic colorectal carcinoma with disease progression along with or following fluoropyrimidine, oxaliplatin and irinotecan chemotherapy regimens. In July, the FDA approved labeling revisions to ImClone Systems and Bristol-Myers Squibb’s Erbitux (cetuximab) and Vectibix, requiring the products to state that they are not recommended to treat colorectal cancer in patients with certain genetic mutations (DID, July 21).

The revisions followed release of guidelines last year by the American Society of Clinical Oncology and the National Comprehensive Cancer Network recommending that all metastatic colorectal cancer patients be tested for KRAS gene mutations prior to treatment with an anti-epidermal growth factor receptormonoclonal antibody therapy such as Erbitux or Vectibix, ImClone says in a statement at the time. — Martin Berman-Gorvine


Sunesis Gets Orphan Designation for AML Treatment Voreloxin

Sunesis Pharmaceuticals’ acute myeloid leukemia (AML) treatment voreloxin has been granted orphan drug status by the FDA.

The drug, a novel naphthyridine analog structurally related to quinolones, which is in Phase II clinical trials, will be eligible for a seven-year period of market exclusivity in the U.S. and an exemption from user fees if it is approved by the agency, Sunesis says in a statement Thursday.

The company is conducting two Phase II trials of voreloxin in patients with AML. The first study, REVEAL-1, is testing the drug in newly diagnosed elderly AML patients unlikely to benefit from standard induction chemotherapy. The other study is evaluating the drug in combination with cytarabine in relapsed/refractory AML.

Sunesis is finalizing a registration strategy for the drug in AML and anticipates launching a pivotal trial in 2010, Steven Ketchum, senior vice president of R&D at Sunesis, says in the statement.

The granting of orphan drug status to voreloxin follows a move by the FDA and the European Medicines Agency to grant the orphan designation to Antisoma’s drug candidate AS1411, also for the treatment of AML, last month (DID, Oct. 14). — David Belian


Investigator Cited for Failing to Report Patient’s Death

A cardiologist working as a clinical investigator failed to report serious adverse events, including a death, to the sponsor in a timely manner, according to an FDA warning letter.

Charles McKay of Torrance, Calif., was cited for his conduct of a drug trial based on an FDA inspection of his site Feb. 24 through March 6. The FDA redacted details about the drug and sponsor from the Oct. 23 warning letter that was posted online Nov. 3.

One of McKay’s patients suffered cardiac arrest, was hospitalized and died — events the site knew of at the time but did not report to the sponsor for about two months, the warning letter says. Another patient was hospitalized for congestive heart failure, which the site also failed to report to the sponsor in a timely manner.

These and other violations cited in the warning letter were traceable to McKay’s failure “to have adequate involvement in and oversight of the study to ensure data integrity and to protect the rights, safety and welfare of subjects,” the FDA says.

In a written affidavit McKay signed during the FDA inspection, he says he thought the training he and his study coordinators were getting from the study monitors was sufficient and that if there were problems, the monitors would let him know, the warning letter says.

In addition, McKay says he did not know he had to supervise the study and ensure that the coordinators were correctly completing source records and case report forms, filling out adverse event and hospitalization forms, and notifying the institutional review board (IRB) and sponsor on time.

He says he did not learn of the problems at the site and start trying to fix them until the fall of 2008. Most of the problems cited in the warning letter occurred in 2007.

The warning letter also cites McKay for:

  • Failure to do follow-up visits and lab tests;
  • Failure to notify the IRB about several protocol changes the sponsor requested until after the study was over;
  • Lack of documentation showing whether the site filed a report about a subject who was hospitalized several times during the course of the study;
  • Inadequate drug disposition records, such as one case in which the site had no information about how much of the study drug a subject had used; and
  • Significant delays in reviewing the results of four subjects’ screening laboratory samples, resulting in their enrolling in the study and receiving the additional drug or completing the entire study, before they were examined.

McKay did not respond to a request for comment by press time. The warning letter can be viewed at www.fda.gov/ICECI/EnforcementActions/WarningLetters/ucm188805.htm. — Martin Berman-Gorvine

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