Staff Writer

Theravance Inc. said that it will need a risk minimization plan to gain FDA approval of its telavancin antibiotic for complicated skin infections, forcing yet another delay.

As a result, the FDA's target date for taking action on telavancin is expected to be pushed later into the year, possibly October, analysts said. South San Francisco-based Theravance is seeking approval of telavancin for two indications: complicated skin structure and skin infections (cSSSI) and hospital-acquired pneumonia (HAP).

In a complete response letter to the company, the FDA outlined its requirements for approval, including a risk evaluation and mitigation strategy (REMS) for telavancin use in cSSSI. The risk plan includes a black-box warning about pregnancy risks, a medication guide and a post-approval registry of pregnant women exposed to telavancin.

The agency also called for data on patients with certain renal risk factors from studies in both cSSSI and HAP. Cowen & Co. analyst Rachel McMinn said in a research note that the FDA is looking to "ensure [that] renal safety data in skin are similar to HAP."

In addition, the agency is seeking revisions to the draft label, including monitoring of renal function and cautionary language regarding the use of telavancin in patients with certain renal risk factors. However, Theravance said that the FDA has not called for any new studies.

"We are very pleased with the continued progress of our application and intend to address these requests promptly," CEO Rick Winningham, said in a statement. "We look forward to finalizing labeling discussions with the FDA in order to bring the benefit of telavancin to patients with these serious infections."

This is the second complete response letter that FDA has issued for telavancin use in skin infection, following an letter issued in October. The latest news was no surprise; however, it was somewhat more positive than analysts had expected.

An FDA advisory panel has voted in favor of telavancin use in cSSSIs, despite concerns about renal, cardiovascular and pregnancy risks. That panel, which met in November 2008, "contemplated a multi-pronged risk plan to address not only pregnancy but also renal and cardiovascular safety," Thomas Russo, an analyst with Robert W. Baird & Co., told BioWorld Today.

Given the advisory panel's discussion, Russo said the requirements outlined by FDA are "probably the best case of the possible outcomes." But he cautioned that the draft labeling has not been finalized and could change in any final approval.

He expects the product launch now will occur in the fourth quarter rather than his original projection of the third quarter.

In its letter, the FDA called for a black box - the agency's strictest warning - in the label to address the potential pregnancy risk. However, it said that the potential kidney (renal) risks could be addressed through cautionary language and patient monitoring.

A maternal health group had sought a tough, universal code "X" in the label to alert women that would steer pregnant woman away from use of the product. But the FDA is requiring a caution code "C" that is viewed as less restrictive.

As Russo explained, the X code excludes a product's use in pregnant women, and is an indication that the risks clearly outweigh any possible benefits. On the other hand, he said, a C code indicates that a risk has been demonstrated in animal studies but there are no studies to conclude one way or the other that it poses a risk to humans. And in such cases, the prescribing is left to the discretion of the physician, Russo said.

McMinn agreed that the C code is "a win" for the company.

However, having a black box "will have to be taken into consideration on the skin side," she told BioWorld Today. "If a woman comes in with a burn, you're probably not going to reach for telavancin."

Analysts view the HAP indication as having a better commercial opportunity due to the scarcity of competitors in that space relative to the number of skin infection products. Currently, there are only two main drugs to fight HAP caused by the bug methicillin-resistant Staphylococcus aureus (MRSA): generic vancomycin and Pfizer Inc.'s Zyvox (linezolid). Both of those products are approved for skin infections as well as pneumonia.

Shares in Theravance (NASDAQ:THRX) gained 81 cents, closing at $13.94 on Friday.

It other FDA actions:

• Salix Pharmaceuticals Ltd., of Raleigh, N.C., received a complete response letter as part of a classwide requirement for all manufacturers of metoclopramide in the U.S. to provide a REMS for their products. As a consequence, the FDA indicated that a REMS for Metozolv, orally disintegrating tablets for gastroesophageal reflux, is required prior to approval of its new drug application. The classwide REMS requirement involves an adverse event of metoclopramide known as tardive dyskinesia, which Salix said is widely known among health care professionals and is well documented in the literature and current labeling of metoclopramide products.

• Somaxon Pharmaceuticals Inc., of San Diego, received a complete response letter in which the FDA raised a number of issues relating to the interpretation of the efficacy data contained in the Silenor NDA and indicated that the FDA was open to a discussion of these concerns. The FDA did not specifically request the company to conduct additional trials of Silenor. The company said it believes that a discussion with the FDA will be necessary to gain a complete understanding of issues raised in the letter, and the company intends to schedule that discussion as soon as possible.