Accentia proposes to move forward with its first phase 3 study on recurrent post-surgical chronic sinusitis patients, and would like to include in its confirmatory phase 3 study additional patients who suffer from moderate to severe chronic sinusitis but have not had surgery, in order to seek an expanded label indication when the drug launches.
As a result of this determination that the IND will remain under the supervision of the Special Pathogens and Transplant Products section of the FDA, Accentia is consulting with that section on its development program for SinuNase, including whether or not it is advisable for the Company to resubmit an application for a special protocol assessment before commencing the first phase 3 study.
On Nov, 14, 2005 Accentia had disclosed that it had been notified by the FDA that its IND for SinuNase might be transferred to another division of the FDA, and the Company disclosed that it had voluntarily withdrawn its submission of a special protocol assessment agreement (SPA) for its first phase 3 study of SinuNase, pending resolution of the proposed transfer.
"A special protocol assessment identifies the exact label claim the clinical trial will support if successful, and it is specific to each phase 3 clinical study," explains Frank E. O'Donnell, Jr., M.D., Chairman and CEO of Accentia. "Both the Company and the FDA agree that statistically significant evidence showing that SinuNase precludes the need to resort to surgery to control severe chronic sinusitis would be beneficial, as there is no approved pharmaceutical intervention for chronic sinusitis."
To conduct the clinical trials, Dr. O'Donnell adds, the Company has identified over 50 investigative sites in the U.S. "We anticipate identifying potential candidates for the studies over the next 90 days. We hope to be able to commence dosing of the first patients by July," he notes. "The upcoming clinical trials of SinuNase are designed to compare patient responses to treatment versus control over a four-month period."
Also, as a result of the decision about the IND remaining with Special Pathogens and Transplant Products, Accentia has filed an amendment to its application for Fast Track status. Chronic sinusitis represents a significant disease affecting 31 million patients and requiring over 500,000 sinus surgeries each year. Moreover, it represents a significant unmet clinical need because there is no pharmaceutical treatment that has been shown to be effective in controlling the disease.
Background on Chronic Sinusitis
Chronic sinusitis (CS), also known as chronic rhino sinusitis (CRS), is one of the most common diseases, affecting an estimated 31 million patients in the U.S. alone. Chronic sinusitis is defined as inflammatory disease of the nasal and sinus mucosa that persists for three months or longer. Long-term consequences include the formation of inflammatory polyps in the nose. Symptoms of inflammation caused by chronic sinusitis include nasal congestion, mouth breathing, nasal discharge, and post-nasal drip. Patients often also experience recurrent bouts of acute bacterial sinusitis, characterized by fever, malaise and pain that require treatments with systemic oral antibiotics and which cause them to miss work or miss school. Although these acute bacterial superinfections typically respond to antibiotics, the chronic underlying condition does not.
The diagnosis and treatment of the underlying chronic sinusitis (CS) or chronic rhino sinusitis (CRS) remains challenging. As we mentioned earlier, there are no prescription pharmaceuticals, including any antibiotics, approved for this condition. Furthermore, the FDA has instructed manufacturers of over-the-counter (OTC) decongestant products claiming to treat sinus disease to stop making these claims for their products by April 2007.
Diagnosis of CS/CRS is based on the patient's history, nasal endoscope examination, and a CT scan of the sinuses. A major obstacle to the rational design of a laboratory diagnostic and pharmaceutical treatment has been the lack of a plausible theory of causation. Accentia Biopharmaceuticals' efforts to develop and commercialize a standard diagnostic test and treatment for chronic sinusitis is based on research at the Mayo Clinic and subsequently published in peer-reviewed journals.
Why Mold Can Cause Problems
Mayo Clinic investigators discovered that Alternaria, a ubiquitous, normally innocuous mold that colonizes the mucus of the nose and sinus of virtually everybody, elicits in patients with chronic sinusitis an eosinophilic (inflammatory) response, characterized by the release of a Major Basic Protein (MBP) in the mucus. This protein damages the mucosal lining of the nose and sinuses, and leads to inflammatory changes in mucosal tissues characteristic of chronic sinusitis. In patients with chronic sinusitis, the MBP of mucin is elevated, while it is undetectable in those who are not susceptible ("normals"), or in patients who have just seasonal or perennial allergic rhinitis.
Based on their laboratory observations and results, investigators at Mayo developed a unique diagnostic test for chronic sinusitis, which involved testing mucin for MBP. Accentia is making this diagnostic available commercially as CRS Fungal Profile. This reference lab test is intended to be an adjunct to the clinical and radiological diagnosis of chronic sinusitis.
Intranasal Application of Amphotericin B
Investigators at Mayo and elsewhere have published small clinical studies on the efficacy and safety of using a low dose antifungal applied intra-nasally. In particular, they have reported on the use of a lavage of 0.01% Amphotericin B for the treatment of the symptoms and signs of chronic sinusitis. With the inciting role that the fungal antigen plays in the chronic inflammatory response of the mucosa, it appears that a muco-administered antifungal takes a few weeks to maximize the response. In one published study at Geneva University, for example, intranasal amphotericin B 0.01% was applied for four weeks, and among patients with partial nasal obstruction from polyposis, about 50% of patients had complete resolution of their polyps.
Under an IND, Accentia is now developing a low dose intranasal lavage formulation of Amphotericin B (SinuNase) for the treatment of the signs and symptoms of chronic sinusitis. The initial study population is in refractory patients who have undergone sinus surgery for chronic sinusitis but who are struggling with recurrent chronic sinusitis. These four-month randomized, double-blind, placebo-controlled clinical trials are designed to test the efficacy and safety of this particular intranasal antifungal for this indication. One of the compelling reasons that Accentia chose Amphotercin B is that it has an extremely low absorption across mucus membranes. Since, in this situation, absorption of the drug into the sinus mucosa is not needed, Sinu Nase's desired site of action will be confined to the mucus layer.
More information on the diagnostic CRS Fungal Profile is available by calling Accentia's laboratory partner, IMMCO, at 800-537-8378. For more information on Accentia and SinuNase please visit www.accentia.com.
About Accentia Biopharmaceuticals, Inc.
Accentia Biopharmaceuticals, Inc. is a biopharmaceutical company focused on the development and commercialization of late-stage clinical products in the therapeutic areas of respiratory disease and oncology. Two of these products are SinuNase and BiovaxID. The Company's SinuNaseTM product, in development to treat chronic sinusitis (rhinosinusitis), is a novel application and formulation of a known anti-fungal licensed from the Mayo Foundation for Medical Education and Research. BiovaxID is a patient-specific anti-cancer vaccine focusing on the treatment of follicular non-Hodgkin's lymphoma. BiovaxID, which is being developed by Accentia's subsidiary Biovest International, Inc., is currently in a Phase 3 clinical trial. In addition, Accentia's growing specialty pharmaceutical business, TEAMM Pharmaceuticals, has a portfolio of currently marketed products plus a pipeline of additional products under development by third parties. For further information, please visit our web site: www.accentia.net.
Forward-Looking Statements
Statements in this release that are not strictly historical in nature constitute "forward-looking statements." Such statements include, but are not limited to, statements about Accentia and any other statements relating to products, product candidates, and product development programs. Such statements may include, without limitation, statements with respect to the Company's plans, objectives, expectations and intentions and other statements identified by words such as "may," "could," "would," "should," "believes," "expects," "anticipates," "estimates," "intends," "plans" or similar expressions. Such forward-looking statements involve known and unknown risks, uncertainties, and other factors that may cause the actual results of Accentia to be materially different from historical results or from any results expressed or implied by such forward-looking statements. These factors include, but are not limited to, risks and uncertainties related to the progress, timing, cost, and results of clinical trials and product development programs; difficulties or delays in obtaining regulatory approval for product candidates; competition from other pharmaceutical or biotechnology companies; and the additional risks discussed in filings with the Securities and Exchange Commission. All forward looking statements are qualified in their entirety by this cautionary statement, and Accentia does not undertake any obligation to revise or update this news release to reflect events or circumstances after the date hereof.
Contacts:
Accentia Biopharmaceuticals, Inc., Tampa, FL
Sherran Brewer: 1-866-481-9020
sbrewer@accentia.net
The Investor Relations Group, New York, NY
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