Advanced Life Sciences Holdings, Inc., a biopharmaceutical company engaged in the discovery, development and commercialization of novel drugs in the therapeutic areas of infection, oncology and respiratory diseases, announced today that FDA has provided guidance on the clinical program required to assess the approvability of Restanza(TM) (cethromycin), a novel oral once-a-day antibiotic, in the treatment of outpatient community acquired bacterial pneumonia (CABP) as well as biodefense indications including anthrax, plague and tularemia.
(Logo: http://www.newscom.com/cgi-bin/prnh/20080218/ALSLOGO) Advanced Life Sciences met with officials from the FDA's Anti-Infectives Division earlier this week to gain clarity on the registration pathway for Restanza. This meeting followed the December 9, 2009 FDA Anti-Infective Drugs Advisory Committee (AIDAC) meeting which discussed clinical trial design issues for CABP relative to the earlier, March 2009, FDA CABP guidance document. In the meeting, the FDA guided that, to assess the approvability for Restanza to treat CABP, the Company should establish a special protocol assessment (SPA) using a superiority clinical trial design comparing Restanza to a marketed macrolide antibiotic in two clinical trials.
In light of this guidance, Advanced Life Sciences is working with the FDA to finalize a SPA using a superiority design for the outpatient CABP indication. Clinical cure rate in a macrolide-resistant Streptococcus pneumoniae (MRSP) population will be the primary endpoint.
"We are pleased that the Agency provided clear guidance regarding our registration pathway for Restanza in the CABP and biodefense indications.
Using clinical response in the MRSP population as the primary endpoint provides the most scientifically meaningful approach to demonstrate a clinical efficacy advantage against resistant strains of Streptococcus pneumoniae," said Michael T. Flavin, Ph.D., chairman and chief executive officer of Advanced Life Sciences. "Based on the data we have accumulated in our extensive pre-clinical and clinical program to date, coupled with a thorough review of published literature on the clinical relevance of macrolide resistance, we believe that Restanza can show a superior efficacy advantage in patients who are resistant to marketed macrolide drugs. With reported macrolide resistance rates as high as 40 percent in the U.S., there is a pressing medical need for new drugs to treat CABP. Our goal is to finalize the SPA by the end of the third quarter of this year." Advanced Life Sciences also announced that it received notice from the Biomedical Advanced Research and Development Authority (BARDA) of the U.S.
Department of Health and Human Services that it has completed its initial technical evaluation of the Company's $15 million funding proposal for advanced development of Restanza as a biodefense countermeasure and identified it as a scientifically and technically sound proposal important to program goals and objectives that may require further development and may be recommended for acceptance subject to funds availability. The Company was invited to submit additional information to allow BARDA to make a final determination on the appropriateness of the proposal to enter into contract negotiations.
Related to this development, Advanced Life Sciences also gained clarity from the FDA on the biodefense regulatory package required for submission in light of recent AIDAC meetings discussing the use of the FDA's Animal Rule for approval of biodefense therapeutics. As anticipated, the FDA recommended that, in parallel with pivotal animal studies demonstrating efficacy under FDA's Animal Rule, Advanced Life Sciences should complete the CABP clinical program and submit a complete response to the CABP new drug application (NDA) prior to submitting an amended NDA for the biodefense indications.
Commented Dr. Flavin: "The goal of our biodefense program is to attract development funding from the U.S. Government that will ultimately lead to the acquisition of Restanza for the Strategic National Stockpile. The notice that we received from BARDA gives us confidence that we can attract additional development funding in the near term and the clearly defined regulatory pathway for the biodefense indications established with FDA will significantly increase our prospects for further development and acquisition contracts with the Department of Health and Human Services and the Department of Defense." Background Advanced Life Sciences submitted the Restanza NDA in September, 2008 based on the results of 53 clinical studies including 2 pivotal phase III studies wherein Restanza demonstrated non-inferiority to Biaxin in mild-to-moderate CABP.
On June 2, 2009, the FDA AIDAC reviewed the Restanza NDA. The AIDAC voted that Restanza demonstrated safety for the outpatient treatment of adults with mild-to-moderate CABP, but voted that Restanza did not demonstrate efficacy in the treatment of CABP in light of the new FDA draft CABP guidance which was published in March of 2009.
On July 31, 2009 the FDA provided a complete response letter to Advanced Life Sciences indicating that further clinical work would be required for the approval of Restanza in CABP. Advanced Life Sciences' pivotal phase III program was designed and conducted under prior FDA guidance and before the new draft guidance document was released.
Over the past two years, the FDA has been conducting public workshops and advisory panels to discuss clinical trial design issues in CABP culminating in a draft guidance document published in March of 2009. Public comments were received in response to the draft guidance and a public AIDAC meeting was held in December of 2009 to further discuss and resolve the CABP clinical design issues.