DID - May 15, 2009 Issue

Vol. 8 No. 95

Sanofi Gets Untitled Letter for Taxotere Journal Reprint Carrier

The FDA cited Sanofi-Aventis for making unsubstantiated superiority claims for its breast cancer chemotherapy Taxotere in a professional journal reprint carrier distributed at the American Society of Clinical Oncology annual meeting last June.

The claims made by the company referenced a reprint from the Journal of Clinical Oncology. The reprint detailed an open-label, randomized, 449-patient trial comparing Taxotere (docetaxel) with paclitaxel, another chemotherapy. The primary endpoint for the study was an objective response, with the secondary endpoints of overall survival, duration of response and time to disease progression.

The journal reprint carrier made multiple claims based on the study — including one that Taxotere was superior to paclitaxel in metastatic breast cancer based on the overall survival, response duration and time-to-disease-progression endpoints, the untitled letter says.

But the study referenced for the product claims did not meet its primary endpoint — statistically significant objective response rates for Taxotere compared with paclitaxel. “In the absence of a finding of statistical significance for the primary endpoint, any further analysis conducted on this study, including secondary endpoints and subpopulations, are all considered exploratory and do not generally constitute substantial evidence,” the FDA says in the letter.

In addition, superiority claims generally must be supported by two well-designed, head-to-head clinical trials, the FDA says. “We are not aware of any study replicating the result achieved in this trial,” the letter says.

Marisol Peron, a spokeswoman for Sanofi, told DID the study was conducted as a postmarketing commitment, and the company believes the contents of the promotion are appropriate. Sanofi is committed to complying with marketing regulations and is working with the FDA on the matter, she added.

The FDA’s Division of Drug Marketing, Advertising and Communications issued the untitled letter April 16. It was posted on the agency’s website Tuesday and can be accessed at www.fda.gov/cder/warn/2009/Taxotere_Letter.pdf. — Christopher Hollis


FDA Sees Oxycodone Shortage Subsiding in June

Shortages of immediate-release tablet formulations of the potent painkiller oxycodone are coming to an end — two additional manufacturers now have the medication available.

“It is anticipated that return to normal supply levels may occur in June,” the FDA says in a Thursday update to its drug shortage website.

Good manufacturing practice (GMP) issues for KV Pharmaceutical and Actavis prompted the shortage, which contributed to demand for other versions of the drug (DID, March 26).

KV recently recalled all of its drug products, including oxycodone, halted production, and entered into a consent decree with the FDA over GMP issues (DID, March 3). Actavis suffered a similar fate. After recalling all drugs made at its facility in Totowa, N.J., including oxycodone, it also entered into a consent decree with the FDA (DID, Dec. 30, 2008). 

KV has yet to resume product shipments. In an April 29 SEC filing, the company tells investors that it does not expect to resume product shipments at least until the fourth quarter.

But production at Actavis’ Totowa site is under way. The FDA recently cleared Actavis to resume production of oxycodone (DID, April 20). The company’s 15- and 30-mg immediate-release tablets are available for purchase.

In addition, Caraco Pharmaceutical Laboratories announced Thursday that it has launched generic versions of Xanodyne Pharmaceuticals’ Roxicodone (oxycodone HCl). Caraco is selling the product on behalf of its parent company, Sun Pharmaceutical Industries.

According to IMS Health, the 5-, 15- and 30-mg strengths of oxycodone tablets had about $160 million in U.S. sales in 2008. More information on the shortage is available at www.fda.gov/cder/drug/shortages/default.htm - Oxycodone. — Christopher Hollis


Clinical Hold Lifted on Stem Cell Therapeutics Stroke Trial

The FDA has lifted the clinical hold imposed last September on Stem Cell Therapeutics’ Phase IIb clinical trial of its investigational product NTx-265 to treat acute ischemic stroke.

The FDA informed the Canadian company verbally that it was lifting the hold, the company says in a statement Thursday. The action will allow Stem Cell to start enrolling patients under an amended protocol.

The clinical hold was lifted following a series of meetings between Stem Cell and the FDA and will be followed by written confirmation from the agency that will help the company finalize its plans, President and CEO Alan Moore said.

NTx-265 combines two approved biologics, human chorionic gonadotropin and erythropoietin. The objectives of the treatment are to stimulate the growth and differentiation of new neurons to replace brain cells lost or damaged by a stroke, and to direct motor, visual and cognitive recovery.

The FDA has been proceeding cautiously with stem cell trials. For example, earlier this year it placed a clinical hold on Neuralstem’s planned Phase I study of a stem cell treatment for patients with amyotrophic lateral sclerosis (DID, Feb. 23). — Martin Berman-Gorvine


Prevacid 24HR Approved to Treat Frequent Heartburn

Novartis and Takeda’s Prevacid 24HR has received FDA approval as an OTC drug to treat frequent heartburn.

Prevacid 24HR (lansoprazole) is the first OTC proton-pump inhibitor (PPI) to be approved for frequent heartburn (occurring two or more days a week) since 2003, according to a Novartis statement Thursday. The drug also is the first OTC PPI to be approved in its original prescription formulation.

The drug is taken daily before breakfast for 14 days and is scheduled to be introduced before the end of the year.

In three clinical studies, Prevacid 24HR demonstrated significantly better efficacy in treating frequent heartburn than placebo, Novartis says. Although some people experience complete relief of symptoms within 24 hours, it may take one to four days for full effect, Novartis adds.

Novartis licensed the rights to develop an OTC version of Prevacid in 2005 from TAP Pharmaceutical, the former joint venture between Takeda and Abbott Laboratories (DID, Dec. 22, 2005). — Martin Berman-Gorvine



UCB Gets FDA Clearance for New Cimzia Indication

The FDA has approved UCB’s Cimzia, a tumor necrosis factor (TNF)-alpha blocker, to treat adults with moderately to severely active rheumatoid arthritis (RA).

The approval was based on trial data showing that combining Cimzia (certolizumab pegol) with methotrexate led to a significant reduction in the signs and symptoms of RA after six months compared with methotrexate alone. Additional data showed the combination slowed the worsening of joint damage, according to a UCB statement.

Cimzia will be available in a pre-filled syringe developed through a collaboration between UCB and Oxo, a consumer products company. The syringe and packaging components take into account some of the challenges many RA patients face when self-administering their medicine, according to the statement.

The product also is approved to reduce the signs and symptoms of Crohn’s disease and maintain clinical response in adults with moderate-to-severe disease who haven’t had an adequate response to conventional therapy. The FDA approved Cimzia for the indication in April 2008 (DID, April 23, 2008). The new pre-filled syringe also will be available for U.S. Crohn’s patients.

In January, the company received a complete response letter for its Cimzia BLA for the RA indication (DID, Jan. 6). During subsequent meetings, the FDA and UCB determined that further clinical trials wouldn’t be necessary (DID, Feb. 9).

Last fall, the FDA instructed four drugmakers, including UCB, to strengthen warnings on patients’ risk of developing opportunistic fungal infections after reports of 12 deaths of patients taking their TNF-alpha blockers (DID, Sept. 5, 2008).

The prescribing information on labels for Cimzia, Amgen’s Enbrel (etanercept), Abbott Laboratories’ Humira (adalimumab) and Johnson & Johnson’s Remicade (infliximab) already included the infection risk.

At the time, UCB told DID it had teams looking at ways to comply with the requirement. The company added that Cimzia has strong warnings regarding infections but it would update the label and inform healthcare providers about the potential for fungal infections. — Elizabeth Jones


EC Approves Teva-Lonza Joint Venture on Biosimilars

The European Commission has cleared the proposed biosimilars joint venture between Teva Pharmaceutical Industries and Swiss drugmaker Lonza.

In reaching its decision, the commission determined that the proposed transaction won’t significantly hinder effective competition in the European Economic Area, according to a statement Thursday.
Teva and Lonza announced their intention to establish the joint venture in January (DID, Jan. 21). At the time, Teva President and CEO Shlomo Yanai said his company was building up its knowledge base and infrastructure to strengthen its position in the biosimilars market, and the partnership would bolster its biologics capabilities.

Lonza manufactures active pharmaceutical ingredients for chemical and biologic products and has the capacity to develop large and small molecules, peptides, amino acids and niche bioproducts.

Both companies plan to explore biosimilars opportunities outside the partnership, according to a joint statement issued in January.

Separately, Teva has received FDA approval for its generic versions of Axcan’s Urso (ursodiol) 250 and Urso Forte for the treatment of primary biliary cirrhosis. Shipment of the products has begun.

The brand products had annual U.S. sales of about $76 million for the 12 months that ended March 31, Teva says in a statement, citing IMS sales data. — Elizabeth Jones

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