Urgent Clinical Need for Alternative Therapy in the Resistant / Intolerant MS Group
June 14, 2004
Source: Hemispherx Biopharma, Inc.
Hemispherx Biopharma, Inc. announced today that it submitted to the FDA a new clinical Protocol entitled "A multi-center, open label, study of Alferon N Injection(R) in subjects with relapsing-remitting multiple sclerosis, who have discontinued interferon-beta therapy because of clinical progression or intolerance, or who have developed neutralizing antibodies to interferon-beta."
Clinical Study Design
A multi-center, open label, phase IIb clinical trial will determine the safety and efficacy of Alferon N Injection(R), a highly purified mixture of natural alpha interferons, in the treatment of multiple sclerosis (MS) patients who have discontinued their treatment of Avonex(R) or Rebif(R) or Betaseron(R) because of clinical progression or intolerance or neutralizing antibody formation. Specifically, the primary endpoint of the study will be annualized clinical relapse rate comparing baseline vs. week 48. Initially, fifty patients selected will be dosed with 5 million IU Alferon N Injection(R) every other day for a period of 48 weeks.
About the Recombinant IFN Market for MS
MS affects about 400,000 individuals in the U.S. and their annualized medication bills are estimated at $4 billion. There is no cure for MS. Interferon beta is the most common treatment for relapsing/remitting disease, which affects 40 percent of MS sufferers. Recombinant, or genetically engineered, interferons are widely used to slow the progression of the illness. Several studies show clear evidence for a beneficial effect in the short term; however, there is no evidence of efficacy after one year of treatment (see below).
About Neutralizing Antibodies
All recombinant beta interferon products have been reported to induce neutralizing antibodies (NAB) in a proportion of the patients that may compromise therapeutic efficacy and long term benefits. In particular, with recombinant interferon (IFN) beta-1b (Betaseron(R)) treatment, approximately one-third of the MS patients develop NAB. In addition, during the first years of treatment with recombinant beta interferons, an increase is observed in the proportion of patients developing NAB. A publication in the Lancet Medical Journal, Vol. 361, Number 9357, year 2003, suggests that in the treatment of MS, virtually all of the recombinant (IFN) therapies seem to lose their benefits after one year. Accordingly, Britain's National Institute for Clinical Excellence (NICE), a cost-effectiveness watchdog, has refused to recommend funding for recombinant interferons for MS patients in the state-run National Health Service because of the controversy over their effectiveness. In view of the reported negative effects of NAB on clinical efficacy and the cross-reactivity among all recombinant beta interferons, there is a growing and urgent need for an alternative therapy, utilizing the interferon mechanism of action which can improve the brain pathology in MS.
To date, no NAB formation has been observed in the treatment with natural alpha interferon (Alferon N Injection(R)) in a large variety of treated diseases, including MS.
About Clinical Progression or Intolerance in MS
At a presentation at the 126th Annual Meeting of the American Neurological Association Chicago, IL (October, 2001), by Professor Sheremata et al, independent clinical researchers found that patients who were intolerant to Betaseron(R) could tolerate Alferon N Injection(R) and that the Alferon N Injection(R) had a similar effect in stabilizing / reducing the disability scores when compared to Betaseron(R) tolerant patients.
About Safety with different IFNs in MS
Severe necrotizing cutaneous lesions complicate the treatment with recombinant interferon beta-1b (Betaseron(R)). Although fever, fatigue, and prominent local reactions are common with interferon beta-1b, prominent skin necrosis seems to be a severe complication. Such severe reactions have not been reported with natural interferon alpha. In an initial clinical study conducted by Professor Sheremata, highly purified, natural interferon alpha, Alferon N Injection(R), was associated with remarkably few local skin reactions in MS (New England Journal of Medicine, Vol. 332:1584).
About Alferon N(R)
Alferon N(R) (Interferon alfa-n3, human leukocyte derived) is a highly purified, natural source, glycosylated, multispecies alpha interferon product, composed of eight forms of highly purified alpha interferon. It is the only natural-source, human multispecies alpha interferon sold in the U.S. and is approved for the treatment of refractory papilloma by various regulatory agencies worldwide. By contrast, recombinant, non-natural source, interferon is composed of only one form and thus lacks the potential for synergistic therapeutic activity.
Hemispherx Biopharma, based in Philadelphia, is a biopharmaceutical company engaged in the manufacture and clinical development of new drug entities for treatment of viral and immune-based chronic disorders. Its flagship products include Alferon N(R) and the experimental immunotherapeutics/antivirals Ampligen(R) and Oragens(TM). These novel proteins, approved for a category of STD infection, and experimental nucleic acids are being developed for globally important chronic viral diseases and disorders of the immune system including HPV, HIV, CFS and Hepatitis. Its platform technology includes large and small agent components for potential treatment of various chronic viral infections. Hemispherx has approximately 270 patents comprising its core intellectual property estate, a fully commercialized product (Alferon N(R)) and GMP certified manufacturing facilities for its novel pharma products. For more information please visit www.hemispherx .net.
Information contained in this news release other than historical information,
should be considered forward-looking and is subject to various risk factors
and uncertainties. For instance, the strategies and operations of Hemispherx
involve risk of competition, changing market conditions, change in laws
and regulations affecting these industries and numerous other factors discussed
in this release and in the Company's filings with the Securities and Exchange
Commission. Any specifically referenced investigational drugs and associated
technologies of the company (including Ampligen(R) and Oragens(TM)) are
experimental in nature and as such are not designated safe and effective
by a regulatory authority for general use and are legally available only
through clinical trials with the referenced disorders. The forward-looking
statements represent the Company's judgment as of the date of this release.
The Company disclaims, however, any intent or obligation to update these
forward-looking statements. Only Clinical Studies under well-controlled
conditions can establish efficacy and safety of any product. Clinical trials
for other potential indications of the approved biologic Alferon(R) do
not imply that the product will ever be specifically approved commercially
for these other treatment indication.
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