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Herpes Treatment
'Although miRNAs encoded by cellular genes are known to be an important mechanism for controlling gene expression, this is one of the first miRNA found to be encoded by a viral genome,' says Fraser. 'Our study helps show how HSV-1 can maintain a latent infection for the lifetime of an infected individual.'
The LAT gene was discovered by Fraser and colleagues in 1984, but a protein product from this gene has never been found. This caused Fraser and his research team to hypothesize that LAT may work through an miRNA molecule, which is a small piece of the LAT gene. It interferes with the translation of two cell proteins that are required for cell death: TGF-b and SMAD-3. The LAT miRNA binds to specific sequences of messenger RNA from these two genes and causes them to be degraded. Thus, the amount of TGF-b and SMAD-3 protein is reduced in the cell and apoptosis is prevented. Because the latent virus is not producing any viral proteins the immune system of the infected individual cannot detect the infected cell.
Latent HSV-1 infections form in neuronal cells of the peripheral nervous system. When a latent infection is reactivated (by stress of many kinds), HSV-1 proteins are synthesized and new infectious virus particles are formed. These virus particles migrate along the neuronal axons to the epithelial cells of the skin. Viral growth in the skin, or other mucous membranes where nerves are found, causes cell damage and an immune reaction that results in a painful sore. Although the latency-to-reactivation process is not fully understood, it is known to involve stress, such as physical damage, ultraviolet light, hormones, or even fever.
Fraser is currently testing whether HSV-2, a relative of HSV-1 that causes genital herpes, also encodes an miRNA molecule in its LAT gene. 'MiRNA may be a more general mechanism that latent viruses use to remain alive in the host cell,' suggests Fraser.
Present treatments of HSV-1 rely on acyclovir-based drugs that target the viral polymerase and inhibit viral DNA replication during the acute infection. However, they do not target the latent infection, and thus cold sores return throughout the lifetime of the infected individual. Finding an miRNA that interacts with the cellular TGF-b pathway during latency offers the first target against the latent infection and offers a profoundly different approach to treatment, concludes Fraser.
The study co-authors are Ananya Gupta, Jarred J. Garner, Praveen Sethupathy, and Artemis G. Hatzigeorgiou, all from Penn. The study was funded in part by grants from the National Institutes of Health.
Herpes Treatment
(Pic)- Girl putting in contact lens in an undated photo from Yahoo Image Search.
NEW YORK (Reuters Health) - Investigators in Miami and San Francisco describe clusters of a serious eye infection called ulcerative keratitis, an ulceration of the cornea, among soft contact lens wearers caused by the fungus Fusarium, which until this year had been considered an unusual condition in the U.S. Reports of both clusters are published in the Archives of Ophthalmology.
An editorial note preceding the articles refers to the recent withdrawal by Bausch & Lomb of its ReNu MoistureLoc contact lens cleaner, because of an association with these infections. The note says those cases "appear to be part of a more global emergence of Fusarium as a vision-threatening organism in otherwise healthy patients."
In the first paper, Dr. Eduardo C. Alfonso and colleagues at the Bascom Palmer Eye Institute in Miami, report that their group treated 10 cases of soft contact lens-associated keratomycosis between 1969 and 1992. But between January 2004 and April 2006, they treated 34 cases attributed to Fusarium infection.
The average age of the patients was 34.9 years (range 13 to 92). Medical histories and evaluations failed to turn up any active disease that would predispose the patients to infectious ulceration.
Thirty-one patients (91 percent) were initially treated with antibiotics for presumed bacterial keratitis; four patients were treated with antiviral medications; and only two received antifungal therapy before the final diagnosis was made.
The average time from onset of symptoms to diagnosis was 9.1 days (range 0 to 140 days). At the initial examination, the size of the infiltrates ranged from 1 to 8 mm.
Once the fungus was identified, patients were usually treated with topical natamycin 5 percent and oral voriconazole 200 mg per day was prescribed to three patients. The length of treatment ranged from 21 to 138 days
One case required placement of tissue adhesive glue, and another required a surgical procedure. Most patients needed corneal scraping to remove dead tissue.
Alfonso's team cautions: "Based on the present report, ophthalmic clinicians should have a heightened clinical suspicion for possible Fusarium and other fungal pathogens as causative agents in cosmetic soft contact lens patients with ulcerative keratitis."
They note that cultures and microscopy are valuable diagnostic tools, and early treatment leads to rapid cure with good outcomes. They recommend a polyene antifungal agent, such as natamycin or amphotericin, applied every hour initially.
Meanwhile, in a small case series reported by Dr. David G. Hwang and associates at the University of California, San Francisco, there were four patients with contact lens-associated Fusarium keratitis during a 5-week span in early 2006. Previously, the department had treated eight cases of Fusarium keratitis between 1976 and 2005, only two of which were associated with contact lens use.
Three of the patients -- ages 19 to 24 years -- had no risk factors for fungal keratitis, whereas a fourth woman, 56 years old, was undergoing chemotherapy for non-Hodgkin lymphoma, which may have lowered her resistance to infection.
Initially two of the patients were misdiagnosed with herpes-related keratitis and the other two with bacterial keratitis. One patient whose diagnosis was not made for at least 4 weeks after symptom onset ended up requiring corneal transplant surgery. Seven weeks later, her visual acuity was still poor.
The other three patients recovered with visual acuity of 20/40 or better after treatment with topical antifungal therapy.
In many of the cases, but not all, patients recalled having used Bausch and Lomb contact lens solutions, which have been pulled from the market.
Hwang's team adds that clusters of cases have been reported in other areas of the U.S. and in Singapore.
SOURCE: Archives of Ophthalmology, June 12, 2006.
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Clinicopathologic Reports, Case Reports, and Small Case Series
Outbreak of Fusarium Keratitis in Soft Contact Lens Wearers in San Francisco
Arch Ophthalmol. 2006;124:(doi:10.1001/archopht.124.7.ecr60006).
We report a cluster of 4 cases of soft contact lens'Cassociated Fusarium keratitis seen at the University of California, San Francisco (UCSF), during a 5-week span in early 2006 and compare this cluster with the number of previous cases of culture-positive Fusarium keratitis seen at UCSF during the prior 30 years. This cluster represents part of a larger outbreak of Fusarium keratitis currently under investigation by public health authorities in Singapore1 and the United States.2 As in these outbreaks under investigation, soft contact lens wear and use of ReNu with MoistureLoc or ReNu MultiPlus (Bausch & Lomb, Rochester, NY) contact lens solution was a common feature of these cases.
Report of Cases
Case 1. A 19-year-old, previously healthy woman was referred in February 2006 for presumed herpes simplex keratouveitis unresponsive to medical therapy. She wore daily-wear soft contact lenses and exclusively used ReNu with MoistureLoc contact lens solution. She was initially seen by her ophthalmologist with complaints of redness, irritation, and foreign body sensation in her left eye that had failed to respond to 1 week of broad-spectrum antibiotic drops prescribed by her optometrist. A presumptive clinical diagnosis of herpes simplex keratouveitis was made, and oral valacyclovir hydrochloride, topical 1% prednisolone acetate, and later oral prednisone were prescribed for worsening keratitis. She worsened over 4 weeks and was referred to the Francis I. Proctor Foundation at UCSF.
Visual acuity at initial examination was hand motions OS. A severe, multifocal, infiltrative stromal keratitis with a 1-mm hypopyon was noted in the left eye. The central and peripheral left cornea was studded with numerous fluffy, 0.2-mm, white infiltrates at all depths of the stroma, accompanied by a dense 3-mm infiltrate in the deep stroma paracentrally. No corneal thinning was noted. Giemsa stain of a corneal scraping showed branching, septated hyphae (Figure 1). Fungal keratitis was diagnosed, and a regimen of topical 5% natamycin, topical 0.15% amphotericin B, and oral itraconazole was started. In addition, the oral prednisone and valacyclovir administration were stopped; the prednisolone, rapidly tapered; and the antibiotic drops, continued.
On identification of the fungal pathogen as being Fusarium, itraconazole administration was stopped and oral voriconazole administration begun. However, a fulminant course of worsening suppuration ensued (Figure 2), and 5 days after initial examination at UCSF, a limbus-to-limbus descemetocele accompanied by multiple small perforations (Figure 3) was noted. An emergency tectonic corneal transplantation was performed, and at the time of surgery, a dense, yellowish membrane filling the anterior chamber was excised. Fusarium was noted on histopathological examination and culture of both the membrane and the cornea, despite the antifungal treatment during the preceding 6 days.
Postoperatively, 1% voriconazole drops were substituted for the natamycin and amphotericin B. Despite the use of topical 1% cyclosporine, graft rejection occurred 3 weeks after surgery. As of 7 weeks postoperatively, visual acuity was counting fingers at 2 ft and the graft remained free of signs of recurrent infection.
Case Series. From February 23, 2006, to March 30, 2006, 4 cases of culture-proven Fusarium keratitis were seen at the Francis I. Proctor Foundation and the Cornea Service of the Department of Ophthalmology at UCSF. All patients used soft contact lenses on a daily-wear basis.
Three of the 4 cases occurred in young (ages 19, 21, and 24 years), otherwise healthy female soft contact lens wearers with no other risk factors for fungal keratitis. All 3 of these patients exclusively used ReNu with MoistureLoc contact lens solution that had been purchased in various locations and at various times in the San Francisco Bay Area. The lot numbers and expiration dates were noted to be different for each of these 3 bottles.
The fourth case occurred in a 56-year-old female soft contact lens wearer undergoing CHOP chemotherapy (cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, prednisone) for non-Hodgkin lymphoma. This patient generally used COMPLETE Moisture Plus No Rub contact lens solution (Advanced Medical Optics, Santa Ana, Calif), but on 1 occasion 2 weeks prior to initial examination, she had also used ReNu MultiPlus, which she kept with her travel supplies.
None of the patients had clinical features that led the examining ophthalmologist to suspect the diagnosis of filamentous fungal keratitis. Two of the cases were presumed to be herpetic keratitis, and the other 2 were presumed to be bacterial keratitis. In 3 of the 4 cases, referral to UCSF was made within 5 days of initial examination, and all 3 of these cases did well, with improvement in best-corrected visual acuity to 20/40 or better after a course of topical antifungal therapy, with or without oral antifungal agents. In 1 of the 4 cases, described earlier, a 4-week delay between initial symptoms and diagnosis occurred, during which the patient was treated with oral and topical corticosteroids, and this patient required corneal grafting for severe keratitis with perforation.
Retrospective review of prior Fusarium keratitis cases seen at our institution disclosed only 8 cases during the previous 30 years (1976-2005). Only 2 of these cases occurred in contact lens wearers.
Comment
This cluster of cases appears to be part of a larger outbreak reported in February 2006 by the Singapore Health Ministry and in April 2006 by the Centers for Disease Control and Prevention (CDC) in the United States.1-2 At our institution, which is located in a temperate climate, Fusarium is an exceptionally uncommon cause of contact lens'Cassociated keratitis, having accounted for only 2 such cases in the 30 years prior to the current episode.
Although the cause of the current outbreak has not yet been identified and is the subject of an ongoing epidemiological investigation by the CDC and other public health authorities, the use of Bausch & Lomb ReNu contact lens solution, and ReNu with MoistureLoc in particular, appears to be a common feature of these cases. In our series, ReNu with MoistureLoc was used exclusively by all 3 patients with no other risk factors for fungal keratitis. The fourth patient, who was immunocompromised because of recent chemotherapy, used at least 2 different contact lens solutions, including Bausch & Lomb ReNu MultiPlus solution. Of the 30 analyzed Fusarium cases reported by the CDC in April 2006, 28 were contact lens wearers.2 Of the 26 of those who recalled using a particular contact lens solution, all identified use of ReNu or a generic contact lens solution manufactured by Bausch & Lomb. Shortly after the CDC report appeared, Bausch & Lomb voluntarily withdrew ReNu with MoistureLoc contact lens solutions from the United States. In February 2006, a cluster of Fusarium cases in contact lens wearers was reported by the Singapore Health Ministry,1 and a strong association with ReNu with MoistureLoc use was noted. This report also led to the withdrawal of ReNu with MoistureLoc contact lens solution from the Singapore and Hong Kong markets.
In a May 5, 2006, press release,3 the CDC reported an update on its ongoing investigation. Of the 58 confirmed cases of Fusarium keratitis for which data collection had been completed, 56 reported using contact lenses. Of these contact lens'Cassociated cases, 32 reported using Bausch & Lomb ReNu with MoistureLoc, 15 reported using Bausch & Lomb ReNu MultiPlus, 7 reported using an unspecified Bausch & Lomb ReNu product, 3 reported using a contact lens solution manufactured by Advanced Medical Optics, and 3 reported using a contact lens solution from Alcon Laboratories (Fort Worth, Tex) (some patients in this report used more than 1 contact lens solution). The CDC noted that the market share of ReNu MultiPlus was 5 times higher than that of ReNu with MoistureLoc, yet the majority of the analyzed Fusarium cases to date involved the use of ReNu with MoistureLoc.
Until this report, it has not been established whether the recent case reports represent a true increase in the incidence of Fusarium keratitis.2 Fusarium is not an uncommon cause of keratitis in tropical and subtropical climates, including those of southeast Asia and south Florida. Up to 35% of microbial keratitis cases reported from south Florida are attributable to fungal pathogens, compared with 1% from New York.4-5 There are relatively few reports of Fusarium keratitis in soft contact lens wearers,6 and the exact incidence of Fusarium keratitis in soft contact lens wearers is unknown. Our report strongly suggests that the current cluster represents an unusual spike over the background incidence of Fusarium keratitis seen during the prior 30 years at our institution. We believe that referral bias and reporting bias are unlikely to account for the increased number of cases seen, since all 4 cases came from established referral sources prior to the public announcement of Fusarium keratitis cases by the CDC.
We, other laboratories, and the CDC are currently investigating the fungicidal properties of the contact lens solutions used by these patients and the genotype characteristics of the Fusarium isolates of these cases in an effort to determine the underlying cause of the current apparent outbreak and whether the Fusarium species from these cases originate from a common strain.
Our case series also emphasizes the importance of corneal cultures in assisting with early diagnosis of microbial keratitis and the poor outcome of Fusarium keratitis when prolonged corticosteroid treatment is administered and appropriate antifungal treatment is delayed.
AUTHOR INFORMATION
Correspondence: Dr Hwang, Cornea Service, Department of Ophthalmology, University of California, San Francisco, 10 Koret Way, K-301, San Francisco, CA 94143-0730 (david.hwang@ucsf.edu
).
Published Online: June 12, 2006 (doi:10.1001/archophthalmol.124.7.ecr60006).
Financial Disclosure: None reported.
Funding/Support: This study was supported in part by unrestricted grants from Research to Prevent Blindness and That Man May See.
Author Contributions: Drs Bernal and Hwang contributed equally to this report.
Acknowledgment: We thank Vicky Cevallos, BS, and Cathy Donnellan, BS, for technical assistance with microbiology studies.
Maria D. Bernal, MD; Nisha R. Acharya, MD; Thomas M. Lietman, MD; Erich C. Strauss, MD; Stephen D. McLeod, MD; David G. Hwang, MD
Herpes Treatment
FermaVir Announces FDA Response to its pre-IND Submission for Initial Bioavailability Studies in Human Clinical Trials of FV-100; Response Enables Company to Plan Clinical Development Program for Novel Antiviral Drug Candidate
NEW YORK--(BUSINESS WIRE)--Jun 5, 2006 - FermaVir Pharmaceuticals, Inc., (OTCBB:FMVR), committed to the development of breakthrough antiviral drugs and other therapies, announced today that the U.S. Food and Drug Administration (FDA) has responded to its pre-Investigational New Drug (IND) application for FV-100, a pro-drug of CF-1743 to address the potentially serious and debilitating viral condition known as shingles. The FDA response will enable FermaVir to proceed with clinical development of FV-100 for the treatment of shingles.
Dosing with FV-100 increases bioavailability of CF-1743, 8 to 10 fold in an animal model compared to dosing with CF-1743 itself. Due to this finding, development of FV-100 as opposed to CF-1743 may have significant benefits in both amount of drug necessary for both therapeutic dosing and manufacturing. Previously, the FDA commented on FermaVir's pre-IND application for CF-1743 in a letter that also included a series of recommendations for the company's drug development program. These FDA recommendations were reconfirmed in the latest response.
The Company has initiated preclinical studies with its proprietary antiviral compound, currently known by its laboratory designation, FV-100, to be followed by clinical studies, as part of a long-term strategic plan for ultimate drug approval and commercialization. Research data suggests that the compound is believed to be 10,000 times more potent than currently approved drug treatments for shingles.
"We are extremely pleased with the FDA's response to our Investigational New Drug application for preclinical and clinical studies related to our novel antiviral compound," said Dr. Geoffrey Henson, CEO of FermaVir. "The guidelines provided will enable us to launch a fast development track for this compound, which we believe has the potential to become a critically needed new antiviral therapy for the treatment of shingles."
FV-100 is among a portfolio of FermaVir's proprietary medical technologies and clinical candidates planned for development to treat a family of viral diseases related to herpes.
"It is encouraging that the Agency's pre-IND letter effectively reinforces FermaVir's planned clinical strategy and anticipated timelines, including bioavailability and safety studies in human clinical trials that we expect to initiate within the second half of this year," said Dr. Henson.
Among FermaVir's other lead drug candidates is a powerful antiviral compound to treat Cytomegalovirus, another potentially debilitating condition in the herpes family.
About FermaVir Pharmaceuticals, Inc.
FermaVir Pharmaceuticals, Inc. is an emerging biotechnology company positioned for rapid growth by developing important antiviral drugs and other treatments in underserved segments of the pharmaceutical development marketplace. The Company's Intellectual Property portfolio includes a number of patent applications and a worldwide exclusive license for potential new drug treatments of infectious diseases. Among FermaVir's lead drug candidates is a breakthrough antiviral treatment that has demonstrated powerful inhibitory activity and may have potential therapeutic benefit for the treatment of shingles, also known as herpes zoster. FermaVir's proprietary compound is believed to be 10,000 times more potent than currently approved shingles drug treatments. FermaVir is also developing a compound that could provide the first improved effective treatment in years for Cytomegalovirus (CMV) infection, a currently incurable viral disease from the herpes family that can threaten eyesight as well as cause severe morbidity and mortality.
Forward-Looking Statements
Certain statements made in this press release are forward looking. Such statements are indicated by words such as "expect," "might," "should," "anticipate" and similar words indicating uncertainty in facts and figures. Although FermaVir believes that the expectations reflected in such forward-looking statements are reasonable, it can give no assurance that such expectations reflected in such forward-looking statements will prove to be correct. As discussed in the Form SB-2 of FermaVir dated March 8, 2006, , actual results could differ materially from those projected in the forward-looking statements as a result of the following factors, among others: uncertainties associated with product development, the risk that FermaVir will not obtain approval to market its products, the risk that FermaVir technology will not gain market acceptance, the risks associated with dependence upon key personnel, and the need for additional financing.
Contact FermaVir Pharmaceuticals, Inc., New York Dr. Geoffrey Henson, 212-413-0802 henson@fermavir.com
Herpes Treatment
Dr. Manfred Beilharz will be traveling from Perth, Australia, where he is the Head of the Nobel Prize winning Department of Microbiology and Immunology, School of Biomedical, Biomolecular and Chemical Sciences, the University of Western Australia. Dr. Beilharz will discuss his research with oral interferon and influenza, including his recent mouse study in which oral interferon protected mice given a lethal influenza challenge. Dr. Beilharz will also discuss his proposed human influenza study and published reports on the efficacy and safety of oral interferon in relapsing-remitting multiple sclerosis.
Dr. Lorenz Lutherer, Professor of Physiology and Internal Medicine at Texas Tech University Health Sciences Center, will discuss his research with oral interferon in idiopathic pulmonary fibrosis (IPF) and his recommendations for the Company's next IPF study.
Shareholders will vote to elect six directors to Board of Directors, including two new directors. The two new nominees on the slate for election to the Company's Board of Directors are:
Mr. Thomas D'Alonzo is a seasoned executive with experience in all major facets of pharmaceutical operations: sales and marketing, manufacturing, quality assurance, finance and licensing, and strategic planning. Mr. D'Alonzo served as President of Pharmaceutical Product Development, Inc., a multi-national clinical research organization with 3,000 employees operating in 14 countries and generating $300 million in revenues from analytical labs and Phase I, II, III and IV clinical trials. Previously, Mr. D'Alonzo was President of Genevec, Inc., a gene therapy biotech company with basic research programs in adenovirus and herpes virus vectors for gene delivery to cells. Before that, Mr. D'Alonzo was President of Glaxo, Inc., the U.S. unit of what is now Glaxo SmithKline plc.
Mr. Thomas Ulie, a Chartered Financial Analyst, has been in the investment field for more than 30 years, and is currently CEO of First Island Capital, Inc., a West Coast-based NASD broker-dealer firm. Mr. Ulie also serves as a director of a number of medical companies and has wide ranging experience in the investment community, having worked in investment banking, money management and research. Prior to First Island Capital, Mr. Ulie was a Senior Managing Director for the Stanford Company, a NYSE member firm. Prior to that, Mr. Ulie was an Associate Director of Bear Stearns & Co.
About Amarillo Biosciences, Inc.
Amarillo Biosciences, Inc. is a U.S. biotechnology firm operating in global partnership with the Hayashibara Group, which also holds 15.5% of Amarillo Biosciences shares and has provided over $17.8 million in loans, grants and equity investments. The Company's primary focus is extensive and ongoing R&D into the use of low-dose, orally administered interferon as a treatment for a variety of conditions, including Sjogren's syndrome, Behcet's disease, and opportunistic infections in patients who are HIV positive. In its 22-year history, ABI has invested nearly $37 million to establish oral interferon as a therapeutic agent. The majority of those funds were invested in clinical trials in an effort to achieve FDA approval for interferon. Additional information is available on the ABI web site at http://www.amarbio.com/.
Herpes Treatment
SIR: Herpes simplex virus encephalitis is the most common fatal sporadic encephalitis in humans.1 Psychiatric symptoms, especially delusions and hallucinations, are not uncommon in herpes simplex virus encephalitis.1
The authors report a 31-year-old woman of South-East Asian origin, with no past or family history of mental illness, who had a diagnosis of herpes simplex virus encephalitis, confirmed by polymerase chain reaction. A magnetic resonance imaging of her head and an electroencephalogram were reported as normal. While on the ward, she was noted to be responding to auditory hallucinations. She was disorientated to time and place. She appeared perplexed and showed emotional lability. She showed no insight into her condition. The Addenbrooke's Cognitive Examination (ACE)2 was administered, yielding a score of 74/100 with impairment evident in orientation, verbal fluency and anterograde and retrograde memory. She was discharged from hospital 6 weeks later and followed up in our neuropsychiatry clinic. Her husband reported that she was not the person she had been. She showed marked apathy, was not interested in looking after her child and spent the whole day sitting on her sofa watching TV. In addition, he said she was experiencing significant memory problems, being unable to remember recent events in her life or people she was used to seeing. Latterly, she would start talking to strangers believing that they were known to her. On examination, she appeared distractible, focusing in turn on different aspects of the room. She showed a rather fatuous affect and occasionally giggled childishly. The authors could not elicit any overt psychotic symptoms. She showed little change over the next 5 months. The authors decided to give her a trial of antipsychotic medication, suspecting that there might have been some hidden psychotic presentation, and she was started on risperidone 1 mg twice daily. After 1 week, the patient showed a marked improvement. She started taking an interest in things around her, began to prepare meals at home and to look after her son. Her husband said that she was no longer misidentifying people. On examination, she was less distractible and slightly more articulate in her responses. The ACE score after treatment was 86/100. Furthermore, she showed some insight, recognizing that something had happened to her and beginning to remember part of her stay in hospital.
The possibility of an underlying psychotic process was raised mainly on account of her distractibility, fatuous affect and the history of misidentification given by her husband. Her rapid response to antipsychotic medication both in terms of her mental state and her functioning adds some support to this claim. The authors think that it is important to consider the possibility of an underlying psychotic illness in patients following herpes encephalitis (HSE) particularly when personality/behavioral changes and cognitive impairment are prominent and even when overt psychotic symptoms appear to be absent. Further cognitive decline after the acute stage of the illness is uncommon,3 and this may also alert to the possibility of an underlying psychotic process. Awareness of such a possibility carries important implications for management and prognosis of the patient.
Herpes Treatment
Biogen Idec (NASDAQ: BIIB) and Elan Corporation, plc(NYSE: ELN) today announced the approval of a supplemental BiologicsLicense Application (sBLA) by the U.S. Food and Drug Administration(FDA) for the reintroduction of TYSABRI(R) (natalizumab) as amonotherapy treatment for relapsing forms of multiple sclerosis (MS)to slow the progression of disability and reduce the frequency ofclinical relapses. TYSABRI will be available upon the completion ofkey activities related to the risk management plan, including FDAreview of educational and training materials, internal validation ofsystems based on final FDA requirements and training of internalpersonnel. As such, the companies anticipate TYSABRI will be availablein July.
The FDA granted approval for reintroduction based on the review ofTYSABRI clinical trial data; revised labeling with enhanced safetywarnings; and a risk management plan (TOUCH Prescribing Program)designed to inform physicians and patients of the benefits and risksof TYSABRI treatment and minimize potential risk of progressivemultifocal leukoencephalopathy (PML). Because of the increased risk ofPML, TYSABRI monotherapy is generally recommended for patients whohave had an inadequate response to, or are unable to tolerate,alternate MS therapies.
"Today represents a significant step forward for people withrelapsing MS. The reintroduction of TYSABRI offers new hope as animportant therapeutic choice for patients living with this disablingdisease. TYSABRI has demonstrated compelling efficacy in MS, and webelieve the TOUCH Prescribing Program, designed in collaboration withthe FDA, will help patients and physicians assess the benefits andrisks of TYSABRI and make informed decisions about therapy," saidJames C. Mullen, Chief Executive Officer, Biogen Idec.
"We are pleased with the FDA's decision to once again make TYSABRIavailable to patients and their families suffering from this chronic,debilitating disease, " said Kelly Martin, Chief Executive Officer,Elan. "There continues to be a significant unmet medical need whereTYSABRI will be an important treatment option. "
Today's action follows a March 8, 2006 unanimous recommendation bythe FDA's Peripheral and Central Nervous System Drugs AdvisoryCommittee to allow the reintroduction of TYSABRI. Biogen Idec and Elanvoluntarily suspended TYSABRI from the U.S. market and all ongoingclinical trials in February 2005 based on reports of PML, anopportunistic viral infection of the brain that usually leads to deathor severe disability.
TOUCH Prescribing Program
TOUCH (TYSABRI Outreach: Unified Commitment to Health) PrescribingProgram was developed in conjunction with the FDA to facilitate theappropriate use of TYSABRI and to assess, on an ongoing basis, theincidence and risk factors for PML and other serious opportunisticinfections associated with TYSABRI treatment. This program representsBiogen Idec and Elan's commitment to making the unique benefits ofTYSABRI available in a responsible manner.
Elements of the TOUCH Prescribing Program include:
-- Revised labeling with a prominent boxed warning of the risk of PML; and warnings against concurrent use of TYSABRI with chronic immunosuppressant or immunomodulatory therapies, and patients who are immunocompromised due to HIV, hematological malignancies, organ transplants or immunosuppressive therapies
-- Mandatory enrollment for all prescribers, central pharmacies, infusion centers and patients who wish to prescribe, distribute, infuse, or receive, respectively, TYSABRI
-- Controlled, centralized distribution only to authorized infusion centers
-- Mandatory FDA-reviewed educational tools for patients and physicians, including a patient medication guide, TOUCH enrollment form and a monthly pre-infusion checklist
-- Ongoing assessment of PML risk and overall safety
-- A 5,000 patient cohort observational study over five years, the TYSABRI Global Observation Program in Safety (TYGRIS)
About TYSABRI
Two-year data from the AFFIRM monotherapy trial showed thattreatment with TYSABRI reduced the risk of disability progression by42% (p is less than 0.001), the primary endpoint of the study, and ledto a 67% reduction (p is less than 0.001) in the annualized relapserate compared to placebo. TYSABRI treatment also resulted in sustainedand statistically significant reductions in brain lesion activity asmeasured by MRI. The two-year data from the SENTINEL add-on trial alsodemonstrated that treatment with TYSABRI in addition to AVONEX(R)(Interferon beta-1a) had a significant effect on disabilityprogression, relapse rate and brain MRI disease activity compared toAVONEX alone.
TYSABRI increases the risk of PML, an opportunistic viralinfection of the brain that usually leads to death or severedisability. Three cases of PML occurred in clinical trial patients whowere concomitantly exposed to immunomodulators (interferon beta in thepatients with MS) or were immunocompromised due to recent treatmentwith immunosuppressants (e.g., azathioprine in the patient withCrohn's disease). Two of the cases were observed in 1,869 patientswith MS treated for a median of 120 weeks. A third case of PMLoccurred among 1,043 patients with Crohn's disease after the patientreceived eight doses. The number of cases is too few and the number ofpatients treated too small to reliably conclude that the risk of PMLis lower in patients treated with TYSABRI alone than in patients whoare receiving other drugs that decrease immune function or who areotherwise immunocompromised. Healthcare professionals should monitorpatients on TYSABRI for any new signs or symptoms that may besuggestive of PML. TYSABRI dosing should be withheld immediately atthe first sign or symptom suggestive of PML.
TYSABRI is contraindicated in patients who have or have had PML orwith known hypersensitivity to TYSABRI or any of its components. InPhase III placebo-controlled trials of TYSABRI in MS, the overallincidence and rate of other infections were balanced betweenTYSABRI-treated patients and controls. Herpes infections were slightlymore common in patients treated with TYSABRI. Commonly reportedinfections with TYSABRI included urinary tract infections, lowerrespiratory tract infections, gastroenteritis and vaginitis. Seriousopportunistic and other atypical infections have been observed inTYSABRI-treated patients, some of these patients were receivingconcurrent immunosuppressants.
The incidence and rate of other serious and common adverse eventsin clinical trials were similarly balanced between treatment groups.Serious events that occurred in TYSABRI-treated patients includedhypersensitivity reactions (e.g., anaphylaxis), depression andgallstones. Appendicitis was more common in patients receiving TYSABRIwith AVONEX. Common adverse events reported in TYSABRI-treatedpatients include infusion reactions, headache, fatigue, joint and limbpain, abdominal discomfort, diarrhea and rash.
For more information about TYSABRI please visit www.biogenidec.comor www.elan.com.
Webcast
The companies will host a joint webcast for the investmentcommunity tomorrow at 8:30 am ET, 1:30 pm GMT, which can be accessedthrough the companies' websites.
About Biogen Idec
Biogen Idec creates new standards of care in oncology, neurologyand immunology. As a global leader in the development, manufacturing,and commercialization of novel therapies, Biogen Idec transformsscientific discoveries into advances in human healthcare. For productlabeling, press releases and additional information about the company,please visit www.biogenidec.com.
About Elan
Elan Corporation, plc is a neuroscience-based biotechnologycompany committed to making a difference in the lives of patients andtheir families by dedicating itself to bringing innovations in scienceto fill significant unmet medical needs that continue to exist aroundthe world.
Elan shares trade on the New York, London and Dublin StockExchanges. For additional information about the company, please visitwww.elan.com.
Herpes Treatment
MARTINSRIED, Germany (AFX) - MediGene AG said it has successfully won a dispute over its patent on herpex simplex viruses, or cancer-killing HSV, at the European Patent Office.
The patent protects a production method for herpes simplex virus-1 vaccines including specific oncolytic herpes simplex viruses (cancer-killing HSV) developed by MediGene.
University College London and the University Court of the University of Glasgow had opposed the patent.
The patent protection will expire in Sept 2011, but in case of marketing
authorization prior to that date, the protection may be extended by up to five years.
MediGene is developing two strains of oncolytic herpes simplex viruses, designed to selectively multiply in tumor cells, thus destroying the tumour.
The NV1020 strain is currently undergoing a clinical phase I/II trial for the treatment of liver metastases from colorectal carcinoma, and the G207 strain is being examined in a clinical phase I trial for the treatment of malignant brain tumour.
ragnhild.kjetland@afxnews.com
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Herpes Treatment
Martinsried/Munich 'C San Diego, . Today the German-American biotech company MediGene AG (Frankfurt, TecDAX, Prime Standard: MDG) has announced that it has successfully repelled the opposition against a patent on HSV in final instance before the Boards of Appeal at the European Patent Office. The patent as maintained protects a production method for herpes simplex virus-1 vaccines including specific oncolytic herpes simplex viruses (cancer-killing HSV) developed by MediGene. The University College of London and the University Court of the University of Glasgow had opposed the patent. The two companies BioVex Ltd., and Crusade Laboratories Ltd., respectively, emerged from these two universities. MediGene had acquired an exclusive license under the patent from the University of Chicago.
MediGene holds the dominating patents in the field of oncolytic herpes simplex viruses, among which the European patent No. EP 0500917 of the University of Chicago defended is also counted. This protection will not expire until September 2011. In case of marketing authorization prior to that date, the protection may be extended by up to five more years.
"We have strengthened our dominating patent portfolio in the field of cancer-killing herpes simplex viruses. With more than ten families of patents, MediGene owns broad patent protection in the field of therapy by means of oncolytic HSV. Due to our strong patent position it is difficult for our competitors to freely operate using this technology. Even the loss of one individual property right would not affect MediGene's predominance', Dr. Peter Heinrich, Chief Executive Officer of MediGene AG, comments.
MediGene's HSV programs: MediGene is developing two strains of oncolytic herpes simplex viruses (HSV). They are designed to selectively multiply in tumor cells, thus destroying the tumor (oncolysis), whereby fewer side effects are expected than in conventional therapies. The NV1020 strain is currently undergoing a clinical phase I/II trial for the treatment of liver metastases from colorectal carcinoma, and the G207 strain is being examined in a clinical phase I trial for the treatment of malignant glioblastoma.
This press release contains forward-looking statements that involve risks and uncertainties. The forward-looking statements contained herein represent the judgment of MediGene as of the date of this release. These forward-looking statements are no guarantees for future performance, and the forward-looking events discussed in this press release may not occur. MediGene disclaims any intent or obligation to update any of these forward-looking statements. MediGeneTM is a trademark of MediGene AG.
- end -
MediGene AG is a publicly quoted (Frankfurt: TecDAX), German-American biotechnology company located in Martinsried, Germany and San Diego, USA. MediGene is the first German biotech company with a drug on the market. The NDA for a second drug is under review. In addition, MediGene has several oncological drug candidates undergoing clinical development, and possesses innovative platform technologies for drug development. MediGene's core competence lies in research into and development of novel approaches for the treatment of various cancer and tumor diseases.
Contact MediGene AG:
Email: investor@medigene.com
Fax: ++49 - 89 - 85 65- 2920
Julia Hofmann/Dr. Georg D?nges, Public Relations Tel.: ++49 - 89 85 65- 3317
Dr. Michael Nettersheim, Investor Relations Tel.: ++49 - 89 - 85 65- 2946
Related Links
MediGene AG
www.medigene.com
Herpes Treatment
The FDA ( U.S. Food and Drug Administration ) has approved the reintroduction of Tysabri ( Natalizumab ) as a monotherapy treatment for relapsing forms of multiple sclerosis to slow the progression of disability and reduce the frequency of clinical relapses.
TYSABRI will be available upon the completion of key activities related to the risk management plan ( TOUCH Prescribing Program ), including FDA review of educational and training materials, internal validation of systems based on final FDA requirements and training of internal personnel.
TOUCH Prescribing Program has been designed to inform physicians and patients of the benefits and risks of Tysabri treatment and minimize potential risk of progressive multifocal leukoencephalopathy.
Biogen Idec and Elan voluntarily suspended Tysabri from the U.S. market and all ongoing clinical trials in February 2005 based on reports of progressive multifocal leukoencephalopathy, an opportunistic viral infection of the brain that usually leads to death or severe disability.
TOUCH Prescribing Program
TOUCH ( TYSABRI Outreach: Unified Commitment to Health ) Prescribing Program was developed in conjunction with the FDA to facilitate the appropriate use of Tysabri and to assess, on an ongoing basis, the incidence and risk factors for progressive multifocal leukoencephalopathy, and other serious opportunistic infections associated with Tysabri treatment.
Elements of the TOUCH Prescribing Program include:
- Revised labeling with a prominent boxed warning of the risk of progressive multifocal leukoencephalopathy, and warnings against concurrent use of Tysabri with chronic immunosuppressant or immunomodulatory therapies, and patients who are immunocompromised due to HIV, hematological malignancies, organ transplants or immunosuppressive therapies
- Mandatory enrollment for all prescribers, central pharmacies, infusion centers and patients who wish to prescribe, distribute, infuse, or receive, respectively, Tysabri
- Controlled, centralized distribution only to authorized infusion centers
- Mandatory FDA-reviewed educational tools for patients and physicians, including a patient medication guide, TOUCH enrollment form and a monthly pre-infusion checklist
- Ongoing assessment of progressive multifocal leukoencephalopathy, risk and overall safety. A 5,000 patient cohort observational study over five years, the Tysabri Global Observation Program in Safety ( TYGRIS )
Two-year data from the AFFIRM monotherapy trial showed that treatment with Tysabri reduced the risk of disability progression by 42% ( p<0.001 ), the primary endpoint of the study, and led to a 67% reduction ( p<0.001 ) in the annualized relapse rate compared to placebo.
Tysabri treatment also resulted in sustained and statistically significant reductions in brain lesion activity as measured by MRI.
The two-year data from the SENTINEL add-on trial also demonstrated that treatment with Tysabri in addition to Avonex ( Interferon beta-1a ) had a significant effect on disability progression, relapse rate and brain MRI disease activity compared to Avonex alone.
Tysabri can increase the risk of progressive multifocal leukoencephalopathy, an opportunistic viral infection of the brain that usually leads to death or severe disability.
Three cases of PML occurred in clinical trial patients who were concomitantly exposed to immunomodulators ( Interferon beta in the patients with multiple sclerosis ) or were immunocompromised due to recent treatment with immunosuppressants ( e.g., Azathioprine in the patient with Crohn's disease ).
Two of the cases were observed in 1,869 patients with multiple sclerosis treated for a median of 120 weeks. A third case of PML occurred among 1,043 patients with Crohn's disease after the patient received eight doses.
The number of cases is too few and the number of patients treated too small to reliably conclude that the risk of progressive multifocal leukoencephalopathy, is lower in patients treated with Tysabri alone than in patients who are receiving other drugs that decrease immune function or who are otherwise immunocompromised.
Tysabri is contraindicated in patients who have or have had progressive multifocal leukoencephalopathy, or with known hypersensitivity to Tysabri or any of its components.
In Phase III placebo-controlled trials of Tysabri in multipel sclerosis, the overall incidence and rate of other infections were balanced between Tysabri-treated patients and controls.
Herpes infections were slightly more common in patients treated with Tysabri.
Commonly reported infections with Tysabri included urinary tract infections, lower respiratory tract infections, gastroenteritis and vaginitis.
Serious opportunistic and other atypical infections have been observed in Tysabri-treated patients, some of these patients were receiving concurrent immunosuppressants.
The incidence and rate of other serious and common adverse events in clinical trials were similarly balanced between treatment groups. Serious events that occurred in Tysabri-treated patients included hypersensitivity reactions ( e.g., anaphylaxis ), depression and gallstones.
Appendicitis was more common in patients receiving Tysabri with Avonex.
Common adverse events reported in Tysabri-treated patients include infusion reactions, headache, fatigue, joint and limb pain, abdominal discomfort, diarrhea and rash.
Herpes Treatment
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