DID - July 16, 2008 Issue

Vol. 7 No. 138

FDA, OHRP Working on Joint IRB Database

The HHS Office for Human Research Protections (OHRP) is working with the FDA on expanding institutional review board (IRB) registration to create a joint database that would have a unified esubmission form, OHRP Director Ivor Pritchard told DID.

“There has been considerable pressure on the FDA to register IRBs, just to know where they are,” Pritchard said. Currently there is no master list of IRBs, and nobody knows how many there are.

There is no timeline for development of the database, and it may not be universal when complete, Pritchard said. For example, it would include IRBs of federal agencies other than HHS that sponsor human subject research, such as the Department of Education, which receive “assurance” from OHRP. However,  a few agencies, such as the Department of Defense, do not participate in the OHRP assurance program, and their IRBs would not be included.

One benefit of the proposed database is that it would encourage federally funded research institutions that do not use external IRBs to do so, Pritchard said. The institutions’ reluctance stems from OHRP’s practice of contacting them if their IRBs are found to be out of compliance, Pritchard said. For example, if a board has inappropriate membership for the research it is reviewing and OHRP contacts the institution, it may make the institution appear to be noncompliant although that is not OHRP’s intention, he added.

With the database in place, OHRP could contact the external IRB directly to inform it about the problem, Pritchard said, which could be helpful in encouraging the use of a single external IRB in multi-site studies.

Separately, OHRP has solicited comments as to whether members of IRBs under its aegis should have education requirements imposed on them. The request for comments can be viewed at www.hhs.gov/ohrp/documents/fedreg20080701.htm. — Martin Gidron


Court Finds for Drugmakers in Hormone Replacement Cases

A New Jersey Superior Court judge has dismissed lawsuits against Wyeth and Pfizer that alleged the companies’ hormone replacement therapies caused breast cancer.

The court found that the plaintiffs in Bailey v. Wyeth, Inc., et al., and DeBoard v. Wyeth, Inc., et al., failed to provide evidence required by the state’s Product Liability Act (PLA) to overcome the presumption of adequacy afforded the FDA-approved labeling on Pfizer’s Provera (medroxyprogesterone acetate) and Wyeth’s Prempro (conjugated estrogens/medroxyprogesterone acetate) and Premarin (conjugated estrogens).

Lauren Handler, a partner with the law firm Porzio, Bromberg & Newman, which represented Wyeth in both cases, called the ruling “a proper application of New Jersey law” and “consistent with a growing body of law around the nation, rejecting challenges to FDA-approved labeling.”

To prove that the defendants had violated the act, the plaintiffs would have had to establish that there was “deliberate concealment or nondisclosure of after-acquired knowledge of harmful effects” or that there was “manipulation of the [postmarket] regulatory process,” according to court documents.

The court also dismissed the plaintiffs’ claims of fraudulent misrepresentation and negligent misrepresentation because they were found to be subsumed by the PLA.

Provera is a progestin product acquired by Pfizer in 2003 with the purchase of Pharmacia, the parent company of Pharmacia & Upjohn. Marketed since 1959, Provera is used to prevent abnormal cell growth in the uterus that can occur in women who use estrogen alone to treat menopausal symptoms.

Premarin and Prempro are used after menopause to reduce moderate-to-severe hot flashes; to help reduce the chances of osteoporosis and to treat moderate-to-severe dryness, itching and burning in and around the vagina.

Earlier this year, a jury in the U.S. District Court for the Eastern District of Arkansas found both Pfizer and Wyeth liable for a woman’s breast cancer and awarded her $2.75 million in compensatory damages (DID, Feb. 27). However, that court recently vacated the award of $19.3 million in punitive damages for the plaintiff, and Wyeth says it will appeal the compensatory damages award.

The Arkansas court’s ruling also vacates a $7.76 million punitive damages award against co-defendant Upjohn. The plaintiff in the case, Donna Scroggin, also is appealing the decision. — Elizabeth Jones


Avastin Sales Growth Aided by Journal Reprints

Despite some concerns over Avastin’s risk-benefit profile for metastatic HER2-negative breast cancer, Genentech reported a solid increase in the portion of oncologists prescribing the biologic for use against the disease.

Overall penetration in the first-line HER2-negative breast cancer market was 35 percent during the second quarter of 2008, up from 25 percent in the prior quarter, the company reported. Roughly 75 percent of Avastin (bevacizumab) use for the disease was at 10 mg/kg, the high dose for that indication, Genentech said.

Sales of the product amounted to $650 million for the quarter, $50 million more than the prior quarter.

Avastin was approved in late February by the FDA as a first-line treatment for metastatic HER2-negative breast cancer when used in combination with paclitaxel chemotherapy (DID, Feb. 25).

The uptake came as the company waits for the FDA’s Division of Drug Marketing, Advertising and Communications (DDMAC) to approve promotional materials for the new indication.

“We launched in breast cancer without the use of commercial material pending DDMAC review,” Ian Clark, vice president of Genentech Commercial Operations, said during the firm’s earnings call earlier this week.

“However, since June 30, our representatives used New England Journal of Medicine [NEJM] reprints of the pivotal E-2100 study when communicating with physicians. We will work through the DDMAC process to make additional promotional materials available to our representatives,” Clark said.

He noted that the NEJM study was comprehensive and the additional value of the DDMAC materials, when they are approved, will not be overwhelming.

Sales of Avastin did not meet RBC Capital Markets’ bullish expectations of $664 million for the second quarter. The investment house lowered its 2008 sales forecast for the biologic by $28 million to $2.78 billion but maintained an upbeat outlook.

“Longer-term, we maintain our positive thesis … based on our expectation for positive Phase III data for Avastin in adjuvant colorectal cancer, which would drive significant new accelerated growth … in 2009 and beyond,” RBC said in an analyst note.

Clark said there were some “residual concerns” regarding the biologic’s risk-benefit profile in breast cancer, stemming from a negative review from the FDA’s Oncologic Drugs Advisory Committee late last year. The committee voted 5–4 that data in the Avastin application did not demonstrate a net clinical benefit for use of the product against the disease (DID, Dec. 7, 2007).

“We are finding as we go around and discuss this with clinicians we can get the majority of folks much more comfortable with that equation,” Clark said. “Good progression to date, but I expect it to be gradual.”

The data in Genentech’s submission demonstrated a statistically significant increase in progression-free survival without a corresponding survival benefit. — Christopher Hollis


EC Gives Thumbs Up to Jerini’s HAE Treatment

The European Commission (EC) has granted marketing authorization to Jerini’s Firazyr to treat hereditary angioedema (HAE), a potentially life-threatening genetic disease characterized by spontaneous and recurring attacks of tissue swelling.

The decision makes Firazyr (icatibant) the first product to be approved in the EU to treat HAE and comes roughly two weeks after Shire announced it would acquire Berlin-based Jerini for roughly $520 million (DID, July 7).

According to Jerini, Shire is the best partner to pursue Firazyr’s EU launch and U.S. approval. Jerini received a not-approvable letter for the drug in April and said in June that it would submit a complete response to the letter in the next three to four months (DID, June 24).

Jerini regained North American development and marketing rights to Firazyr last September after its U.S. affiliate and Kos Life Sciences terminated a licensing agreement for the drug. The termination came after Abbott, which purchased Kos in December 2006, determined the drug did not fit its core areas of therapeutic expertise.

Firazyr has been granted orphan drug status by the European Medicines Agency and the FDA. — Elizabeth Jones


Association of the British Pharmaceutical Industry Suspends Roche

Inappropriate sales of Xenical to a proprietor of diet clinics and payments to fund the owner’s purchase of another clinic prompted the Association of the British Pharmaceutical Industry (ABPI) to suspend Roche’s membership for six months.

The allegations concerned activities that took place between 2003–2005, according to the Prescription Medicines Code of Practice Authority (PMCPA), a group that administers the trade group’s code of practice.

“The panel considered that the arrangements brought discredit upon the pharmacutical industry,” a PMCPA panel concluded.

Although the clinic supplied Roche with a valid general medical council number of a physician, Roche violated the ABPI code by supplying Xenical (orlistat) to the diet clinics’ owner, who sold the medication directly to patients. The owner of the clinics claimed to be a licensed pharmacist, but he was not.

“With regard to the supply of Xenical, the panel was extremely concerned about the circumstances, which had led to a prescription-only medicine, in effect, being supplied to a person who was not a health professional, and by that person to patients,” the panel said.

Xenical, sold as OTC weight-loss agent Alli by GlaxoSmithKline in the U.S., is a prescription medication in the UK.

Roche also agreed to give the owner payments totaling £55,000 — £20,000 in August 2004 and £35,000 in January 2005 — to fund the purchase of an additional clinic, for which the owner virtually guaranteed the sale of 2,000 packs of Xenical on a monthly basis once patients at the new clinic were switched to the drug, the panel said.

“The panel considered that the proposed payment of £55,000 for the new diet clinic was linked to the use of Xenical,” the PMCPA panel said. “It was difficult to see how providing £55,000 to an individual to purchase a private diet clinic was a medical and educational good or service that would enhance patient care or benefit the [National Health Service] as required by the code.”

The second payment was never made because the UK’s Medicines and Healthcare product Regulatory Agency (MHRA) contacted Roche regarding suspicions of fraudulent activity at the clinic, the company said.

In March 2005, the agency asked Roche to continue supplying medicine while MHRA investigated the clinic. The agency subsequently cleared Roche of wrongdoing.

Roche’s suspension from the ABPI was effective Monday. To be reinstated, the company must pass an audit scheduled in September.

As a result of the suspension, the company can no longer participate in ABPI forums and meetings, the company told DID.

Roche said it was committed to complying with the ABPI code of conduct and has revised its standard operating procedures to make them fit with that code. The company said it is rolling out a detailed training program for employees as well. — Christopher Hollis

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