FDA Approvals & News
Scalp Psoriasis Treatment Approved
The FDA has approved the new drug application for calcipotriene 0.005% and betamethasone dipropionate 0.064% (Taclonex Scalp Topical Suspension). Taclonex Scalp is a topical suspension containing a combination of calcipotriene 0.005% and betamethasone dipropionate 0.064% for the treatment of moderate to severe psoriasis vulgaris of the scalp in adults.
BLA for Reloxin Accepted
The FDA has accepted the filing of a biologics license application for Reloxin, a botulinum toxin type A agent from Ipsen and Medicis. Reloxin is approved for aesthetic indications in 23 countries.
First Generic Calcipotriene Topical Solution
The FDA has granted approval for the first generic calcipotriene topical solution 0.005% (Scalp Solution). The product from
Fougera is in a formulation that compares to Dovonex by Warner-Chilcott.
Fougera’s Calcipotriene Topical Solution is indicated for the topical treatment of chronic, moderately severe psoriasis of the scalp, and it is available in a 60-ml bottle.
FDA Clearance for Skin Treatment Platform
The FDA granted clearance for Alma Laser’s Harmony (XL), a platform for aesthetic laser and light treatments.
The upgraded Harmony system combines lasers, pulsed light and near-infrared technologies. Multiple exchangeable handpieces enable treatment of more than 60 aesthetic indications and applications. These include acne, skin rejuvenation, hair removal, varicose veins, stretch marks, tattoo removal, wrinkles and skin tightening.
News & Trends
Product Mixup Prompts Medicis to Recall Solodyn
Medicis Pharmaceutical Corporation has announced a voluntary recall of lot numbers B080037 (Exp: 12/09) and B080038 (Exp: 12/09) of the antibiotic SOLODYN (minocycline HCl, USP) Extended Release Tablets, 90 mg, 30-count bottles (NDC 99207-461-30).
The announcement was made after Medicis received a report that one bottle in lot number B080037 contains AZASAN (azathioprine tablets) 75 mg (NDC 65649-231-51) instead of SOLODYN (minocycline HCl, USP) Extended Release Tablets, 90 mg. AZASAN, which is an immuno-suppressive agent used in transplant patients to prevent kidney rejection and for the treatment of rheumatoid arthritis, presents a potential health hazard and safety risk to patients. Side effects associated with the use of AZASAN, particularly in the elderly, include mylosuppression, infection, bleeding, chills, nausea, vomiting and diarrhea. Joint and muscle pain are also common side effects. Unanticipated interactions with other drugs may also lead to serious adverse events.
Any inquiries related to this recall should be addressed to Stericycle Customer Service at 1-888-656-6381 with representatives available Monday through Friday, 8 a.m. to 11 p.m. EST. For any medical information inquiries or to report an adverse event related to this recall, contact Medicis at 1-800-900-6389 with representatives available 24 hours a day, 7 days a week.
This recall is being conducted in cooperation with the contract manufacturer of the products and with the knowledge of the FDA.
Any adverse reactions experienced with the use of this product, and/or quality problems, also may be reported to the FDA's MedWatch Program by phone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, by mail at MedWatch, FDA, 5600 Fishers Lane, Rockville, MD 20852-9787, or on the MedWatch website at www.fda.gov/medwatch.
CDC Recommends Shingles Vaccine for Those Over Age 60
The U.S. Centers for Disease Control and Prevention has adopted the recommendation of its Advisory Committee on Immunization Practices calling for the use of Merk’s ZOSTAVAX, currently the only vaccine to prevent shingles, in adults aged 60 and older.
The ACIP recommendations call for routine vaccination with a single dose of this zoster vaccine for all appropriate candidates 60 years of age and older.
The recommendation targets people who have reported a previous episode of shingles in addition to those with chronic medical conditions for whom the vaccine is deemed safe. Vaccinees should be informed of the potential risk of transmitting the vaccine virus to varicella-susceptible individuals, including pregnant women who have not had chickenpox.
UK Scientists May Be Close to MRSA Cure
A British pharmaceutical has raised hopes of a cure for MRSA within 3 years.
Destiny Pharma presented this promising new drug as a nasal gel — initially to be known as XF-73 — for the first time at the annual European Conference of Clinical Microbiology and Infectious Diseases in Barcelona.
The new compound, which is is not yet approved by the National Institute for Clinical Excellence, is currently in trials. It works differently than anti-MRSA drugs that prevent the bacterium from growing and breeding in that it is designed to actually kill the microbes.
Trials
Five of the most common strains of MRSA were tested against the drug. A topical antibiotic was used as a control.
Both XF-73 and the antibiotic were separately exposed to the strains of MRSA 55 times, over as many days. Each time 99% of the bacteria were destroyed, leaving the strongest 1% to survive.
This was allowed to grow again before being exposed to the XF-73 and the control antibiotic. The scientists then measured how much of the drug was needed to kill the same amount of bacteria for each exposure.
In human trials, the compound is contained in a tiny amount of gel placed inside the nostril, which would prevent the spread of MRSA in hospitals and in the community. Company officials forsee the use of tablet and injection forms of XF-73 within a few years.
Hope for the Future
By 2011, XF-73 could be used to prevent the spread of infection in hospital wards, say researchers. Within 6 years, they claim, it could routinely cure patients already infected with MRSA.
Elesclomol Study Shows Significant Improvement in Progression-Free Survival for Chemotherapy-Naive Patients With Metastatic Melanoma
GlaxoSmithKline and Synta Pharmaceuticals Corp. announced positive Phase II clinical data for elesclomol (formerly STA-4783), an investigational agent currently in development for metastatic melanoma.
Chemotherapy-Naive Patients
A retrospective analysis showed that stage IV metastatic melanoma patients treated with elesclomol and paclitaxel who had not previously received chemotherapy had a statistically significant improvement in progression-free survival compared to patients who received paclitaxel alone.
This retrospective subgroup analysis of a randomized, double-blind, active-controlled, Phase II trial in patients with stage IV metastatic melanoma evaluated the rates of progression-free survival and overall survival for the combination of elesclomol and paclitaxel versus paclitaxel alone in patients who received one prior chemotherapy treatment with those who were chemotherapy-naive. A total of 81 patients evaluated in this analysis either received 213 mg/m2 of elesclomol co-infused with 80 mg/m2 paclitaxel or 80 mg/m2 of paclitaxel alone in 4-week cycles (once weekly for 3 weeks and 1 week's rest) until disease progression.
Patients who had not received prior chemotherapy and were given a combination of elesclomol and paclitaxel (n=24), compared to patients who were given paclitaxel alone (n=8).
Patients With Prior Chemotherapy
Data for patients on the elesclomol and paclitaxel arm who had one prior chemotherapy showed a trend toward results similar to patients who had received no prior chemotherapy; however these data were not statistically significant. Specifically, after receiving one prior chemotherapy, the median PFS was 2.8 months for patients receiving elesclomol and paclitaxel (n=29) versus 1.8 months for patients on paclitaxel alone (n=20; P=0.552), and OS was 9.0 months for patients on elesclomol and paclitaxel versus 7.8 months for patients on paclitaxel alone.
Adverse Events
Regardless of prior chemotherapy, the most common adverse events in the elesclomol plus paclitaxel group included fatigue, alopecia, constipation, nausea, hypoaesthesia, arthralgia, insomnia, diarrhea and anemia. The most serious adverse events (Grade 3 or higher) for the combination arm were similar to those seen in the paclitaxel-only arm and included neutropenia, back pain, fatigue and neuropathy.
These data will be presented at the 44th Annual Meeting of the American Society of Clinical Oncology in Chicago in a poster entitled Phase II Trial of Elesclomol and Paclitaxel in Stage IV Metastatic Melanoma: A Subgroup Analysis By Prior Chemotherapy (Abstract # 9036).
Scientists Identify Factor Key To Severity Of Community-Associated Methicillin-Resistant Staph Infections
According to scientists led by Michael Otto, Ph.D., at the National Institute of Allergy and Infectious Diseases (NIAID), a key process that ensures the survival of S. aureus and causes severe disease involves members of the phenol-soluble modulin (PSM) protein family. The protein first attracts and then destroys protective human white blood cells in drug-resistant strains of the Staphylococcus aureus bacterium.
Their study describing how these proteins help determine disease severity and eliminate immune defense mechanisms against CA-MRSA was published online in "Nature Medicine,” by Dr. Otto and his colleagues at NIAID's Rocky Mountain Laboratories (RML).
Panton-Valentine Leukocidin
Up until a year ago, most scientists studying S. aureus believed they had narrowed their search for the cause of severe CA-MRSA infections, focusing on the Panton-Valentine leukocidin (PVL) toxin produced by certain strains. But then last year, Dr. Otto and his RML colleagues published a study indicating that PVL does not play a major role in CA-MRSA infections.
Role of PSM in Staphylococcus Infection
Dr. Otto's group continued its search to understand why the CA-MRSA strains cause widespread and often severe infections in otherwise healthy people. The RML group identified previously unknown PSMs secreted by S. aureus and identified the genes that encode those PSM proteins. They then compared PSM production between CA-MRSA and the most prominent hospital-associated MRSA strains. The research team found PSM genes in all MRSA strains, but production of the proteins was typically higher in CA-MRSA strains known for severe virulence, according to Dr. Otto.
Focus on Virulence
To determine whether PSMs contribute to virulence, the scientists developed test strains using the most widespread isolates of CA-MRSA, called USA300 and USA400. Each test strain had a certain combination of PSM-encoding genes removed so the researchers could ascertain whether those genes affected virulence.
The scientists then observed how laboratory mice responded to the test strains. By doing so, they pinpointed the "psm-alpha" gene cluster (which makes PSM-alpha protein) as playing an essential role in determining CA-MRSA virulence and, ultimately, disease severity.
To understand how PSMs contribute to virulence, Dr. Otto and colleagues next examined the role of the molecules in S. aureus evasion of human immune defenses. They observed that the "psm-alpha" genes generated the most resistance activity and the PSM-alpha proteins were best at destroying most immune cells that help protect against infection and disease. In all instances, the PSM-alpha molecules caused the greatest destruction of white blood cells, an effect that occurred rapidly.
Scientists ‘Reprogram’ Skin Cells into Stem Cells
In a breakthrough that could ease ethical issues related to the use of human embryos, two teams of scientists working separately believe they have created embryonic stem cells without having to make or destroy an embryo.
According to the research teams – one Japanese and one American from Wisconsin – this accomplishment involved the addition of four genes, which they say, reprogrammed the chromosomes of the skin cells, converting them into blank slates like embryonic cells, which should be able to turn into any of the 220 cell types of the human body.
The two independent teams maintain that their method also creates stem cells that genetically match the donor without cloning. If stem cells are used to make replacement cells and tissues for patients, it would be invaluable to have genetically matched cells because they would not be rejected by the immune system.
Even more important is that genetically matched cells from patients will enable scientist to study complex diseases, like Alzheimer’s, in the lab.
While both groups used just four genes to reprogram human skin cells, two of the four genes used by the Japanese scientists were different from two of the four used by the American group. All the genes in question, though, act in a similar way – they are master regulator genes whose role is to turn other genes on or off.
About 4 years ago, Dr. Shinya Yamanaka of Kyoto University and James Thomson of the University of Wisconsin-Madison, independently launched their respective searches for genes being used in an embryonic stem cell that are not being used in an adult cell to determine whether those genes would reprogram an adult cell.
Dr. Yamanaka worked with mouse cells, and Dr. Thomson worked with human cells from foreskins.
The researchers found more than 1,000 candidate genes. So both groups took educated guesses, trying to reduce the number of genes to the few dozen they thought might be the crucial ones and then questioning whether any combinations of those genes could turn a skin cell into a stem cell.
In Brief…
STIEFEL LABORATORIES, INC. ACQUIRES… ABR INVENT AND ABR DEVELOPMENT through a definitive stock purchase agreement. Stiefel plans to launch ABR’s Atlean dermal filler, which is currently commercialized in France and Italy, in multiple areas Atlean dermal filler in multiple areas, including parts of Europe, Asia Pacific, Latin America and the Caribbean. All sales representatives formerly employed by ABR Development will now become employees of Stiefel Laboratories.
Medimetriks Pharmaceuticals, Inc. … Begins Operations. The newly-formed Company, led by the founder and the key Senior Management Team of the former Bradley Pharmaceuticals will develop, license and commercialize innovative prescription products for the dermatology and podiatry marketplaces.
BARRIER THERAPEUTICS AND PROCTER & GAMBLE … AGREE to market Xolegel (ketoconazole, USP) Gel, 2% with Head & Shoulders Shampoo as Xolegel Duo The kit, which will be available by prescription in June, offers patients a complete treatment regimen for seborrheic dermatitis.
FDA Cleared
New Excimer Laser Cleared for Skin Dermatoses
FDA has granted 510K clearance to PhotoMedex’s XTRAC Velocity excimer laser system for the treatment of psoriasis, vitiligo, atopic dermatitis and leukoderma.
The XTRAC Velocity laser system delivers the highest UV power of any medical excimer laser available today, according to PhotoMedex, and does so with the same reliability and efficacy of its predecessor, the XTRAC Ultra.
The Velocity laser system is up to 3 times faster per treatment, according to company literature.
In February 2007, the BlueCross/BlueShield Association issued a national reference policy stating that targeted phototherapy (including the XTRAC) may be considered medically necessary for treating moderate to severe psoriasis comprising less than 20% body area for which narrow-band-UVB or psoralen plus UVA are indicated.
PhotoMedex developed the first FDA-approved laser treatment for psoriasis.
Birth Defects Associated with Mycophenolate Mofetil
New reports of serious congenital malformations, including microtia and cleft lip and palate, have emerged in infants whose mothers were exposed to mycophenolate mofetil (MMF) during pregnancy.
The active drug substance in CellCept, MMF, is an ester of the active metabolite mycophenolic acid (MPA), the active drug substance in Myfortic.
In most of the cases, the mothers were taking MMF following an organ transplant to prevent organ rejection. However, some mothers taking MMF were being treated for immune-mediated conditions such as systemic lupus erythematosus and erythema multiforme.
They were treated before becoming pregnant, and their treatments continued into the first trimester of their pregnancies or until the pregnancy was realized.
MMF and MPA increase the risk of spontaneous abortion in the first trimester and can cause congenital malformations in the offspring of women who are treated during pregnancy, and labeling for these drugs was revised in November 2007 when the pregnancy category was changed to “D” — positive evidence of human fetal risk. However, potential benefits may warrant use of the drug in pregnant women despite the potential risk.
FDA is continuing to work with the manufacturers of these drug products to develop and implement means to mitigate the risks of fetal exposure.
Clearance for Dual-Pulsed nd:YAG Laser
Lutronic has received FDA approval for its Spectra III multiple laser wavelength system. This dual-pulsed nd:YAG laser, the successor to the Spectra VERM II, removes epidermal and dermal pigmented lesions, including all types of tattoo colors.
Described as the most powerful laser in its class, according to the company, the Spectra III can be used for treating cosmetic and medical conditions for dermatologic and general surgical procedures involving coagulation and hemostasis.
New Type of Latex Cleared
The first device made from a new form of natural rubber latex has been cleared for marketing by the FDA.
Known as guayule latex, the material is derived from the guayule bush, which is found in the desert in the southeastern United States, to make the Yulex Patient Examination Glove (Yulex Corporation).
Traditional latex gloves are made from the milky sap of a rubber tree, Hevea braziliensis, and anywhere from 3% to 22% of all healthcare workers are sensitized to traditional latex. Available data on the new guayule latex show that even people who are highly allergic to traditional latex do not react on first exposure to guayule latex proteins.
Because there are no data on people’s long-term experience with the Yulex glove, the product will carry a warning for now about the potential for allergic reactions.
Other Drug News
Shingles Vaccine Recommended
The U.S. Centers for Disease Control and Prevention (CDC) is recommending that all appropriate people 60 years of age and older receive routine vaccination with a single dose of zoster vaccine line (Zostavax) to help prevent shingles. Zostavax is indicated for the prevention of herpes zoster (shingles) in people 60 years of age and older, and the vaccine has been included on the CDC’s 2007-2008 Recommended Adult Immunization Schedule.
The recommendations for vaccination include the following:
• People who report a previous episode of shingles and people with chronic medical conditions can be vaccinated — unless contraindications or precautions apply to their receiving Zostavax due to their conditions.
• Zostavax is not indicated for the treatment of shingles or postherpetic neuralgia (PHN), and the vaccine should not be to prevent people who have shingles from developing PHN.
• Healthcare providers do not need to ask patients about their history of varicella or conduct serologic tests for varicella immunity.
FDA Approvals & News
Scalp Psoriasis Treatment Approved
The FDA has approved the new drug application for calcipotriene 0.005% and betamethasone dipropionate 0.064% (Taclonex Scalp Topical Suspension). Taclonex Scalp is a topical suspension containing a combination of calcipotriene 0.005% and betamethasone dipropionate 0.064% for the treatment of moderate to severe psoriasis vulgaris of the scalp in adults.
BLA for Reloxin Accepted
The FDA has accepted the filing of a biologics license application for Reloxin, a botulinum toxin type A agent from Ipsen and Medicis. Reloxin is approved for aesthetic indications in 23 countries.
First Generic Calcipotriene Topical Solution
The FDA has granted approval for the first generic calcipotriene topical solution 0.005% (Scalp Solution). The product from
Fougera is in a formulation that compares to Dovonex by Warner-Chilcott.
Fougera’s Calcipotriene Topical Solution is indicated for the topical treatment of chronic, moderately severe psoriasis of the scalp, and it is available in a 60-ml bottle.
FDA Clearance for Skin Treatment Platform
The FDA granted clearance for Alma Laser’s Harmony (XL), a platform for aesthetic laser and light treatments.
The upgraded Harmony system combines lasers, pulsed light and near-infrared technologies. Multiple exchangeable handpieces enable treatment of more than 60 aesthetic indications and applications. These include acne, skin rejuvenation, hair removal, varicose veins, stretch marks, tattoo removal, wrinkles and skin tightening.
News & Trends
Product Mixup Prompts Medicis to Recall Solodyn
Medicis Pharmaceutical Corporation has announced a voluntary recall of lot numbers B080037 (Exp: 12/09) and B080038 (Exp: 12/09) of the antibiotic SOLODYN (minocycline HCl, USP) Extended Release Tablets, 90 mg, 30-count bottles (NDC 99207-461-30).
The announcement was made after Medicis received a report that one bottle in lot number B080037 contains AZASAN (azathioprine tablets) 75 mg (NDC 65649-231-51) instead of SOLODYN (minocycline HCl, USP) Extended Release Tablets, 90 mg. AZASAN, which is an immuno-suppressive agent used in transplant patients to prevent kidney rejection and for the treatment of rheumatoid arthritis, presents a potential health hazard and safety risk to patients. Side effects associated with the use of AZASAN, particularly in the elderly, include mylosuppression, infection, bleeding, chills, nausea, vomiting and diarrhea. Joint and muscle pain are also common side effects. Unanticipated interactions with other drugs may also lead to serious adverse events.
Any inquiries related to this recall should be addressed to Stericycle Customer Service at 1-888-656-6381 with representatives available Monday through Friday, 8 a.m. to 11 p.m. EST. For any medical information inquiries or to report an adverse event related to this recall, contact Medicis at 1-800-900-6389 with representatives available 24 hours a day, 7 days a week.
This recall is being conducted in cooperation with the contract manufacturer of the products and with the knowledge of the FDA.
Any adverse reactions experienced with the use of this product, and/or quality problems, also may be reported to the FDA's MedWatch Program by phone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, by mail at MedWatch, FDA, 5600 Fishers Lane, Rockville, MD 20852-9787, or on the MedWatch website at www.fda.gov/medwatch.
CDC Recommends Shingles Vaccine for Those Over Age 60
The U.S. Centers for Disease Control and Prevention has adopted the recommendation of its Advisory Committee on Immunization Practices calling for the use of Merk’s ZOSTAVAX, currently the only vaccine to prevent shingles, in adults aged 60 and older.
The ACIP recommendations call for routine vaccination with a single dose of this zoster vaccine for all appropriate candidates 60 years of age and older.
The recommendation targets people who have reported a previous episode of shingles in addition to those with chronic medical conditions for whom the vaccine is deemed safe. Vaccinees should be informed of the potential risk of transmitting the vaccine virus to varicella-susceptible individuals, including pregnant women who have not had chickenpox.
UK Scientists May Be Close to MRSA Cure
A British pharmaceutical has raised hopes of a cure for MRSA within 3 years.
Destiny Pharma presented this promising new drug as a nasal gel — initially to be known as XF-73 — for the first time at the annual European Conference of Clinical Microbiology and Infectious Diseases in Barcelona.
The new compound, which is is not yet approved by the National Institute for Clinical Excellence, is currently in trials. It works differently than anti-MRSA drugs that prevent the bacterium from growing and breeding in that it is designed to actually kill the microbes.
Trials
Five of the most common strains of MRSA were tested against the drug. A topical antibiotic was used as a control.
Both XF-73 and the antibiotic were separately exposed to the strains of MRSA 55 times, over as many days. Each time 99% of the bacteria were destroyed, leaving the strongest 1% to survive.
This was allowed to grow again before being exposed to the XF-73 and the control antibiotic. The scientists then measured how much of the drug was needed to kill the same amount of bacteria for each exposure.
In human trials, the compound is contained in a tiny amount of gel placed inside the nostril, which would prevent the spread of MRSA in hospitals and in the community. Company officials forsee the use of tablet and injection forms of XF-73 within a few years.
Hope for the Future
By 2011, XF-73 could be used to prevent the spread of infection in hospital wards, say researchers. Within 6 years, they claim, it could routinely cure patients already infected with MRSA.
Elesclomol Study Shows Significant Improvement in Progression-Free Survival for Chemotherapy-Naive Patients With Metastatic Melanoma
GlaxoSmithKline and Synta Pharmaceuticals Corp. announced positive Phase II clinical data for elesclomol (formerly STA-4783), an investigational agent currently in development for metastatic melanoma.
Chemotherapy-Naive Patients
A retrospective analysis showed that stage IV metastatic melanoma patients treated with elesclomol and paclitaxel who had not previously received chemotherapy had a statistically significant improvement in progression-free survival compared to patients who received paclitaxel alone.
This retrospective subgroup analysis of a randomized, double-blind, active-controlled, Phase II trial in patients with stage IV metastatic melanoma evaluated the rates of progression-free survival and overall survival for the combination of elesclomol and paclitaxel versus paclitaxel alone in patients who received one prior chemotherapy treatment with those who were chemotherapy-naive. A total of 81 patients evaluated in this analysis either received 213 mg/m2 of elesclomol co-infused with 80 mg/m2 paclitaxel or 80 mg/m2 of paclitaxel alone in 4-week cycles (once weekly for 3 weeks and 1 week's rest) until disease progression.
Patients who had not received prior chemotherapy and were given a combination of elesclomol and paclitaxel (n=24), compared to patients who were given paclitaxel alone (n=8).
Patients With Prior Chemotherapy
Data for patients on the elesclomol and paclitaxel arm who had one prior chemotherapy showed a trend toward results similar to patients who had received no prior chemotherapy; however these data were not statistically significant. Specifically, after receiving one prior chemotherapy, the median PFS was 2.8 months for patients receiving elesclomol and paclitaxel (n=29) versus 1.8 months for patients on paclitaxel alone (n=20; P=0.552), and OS was 9.0 months for patients on elesclomol and paclitaxel versus 7.8 months for patients on paclitaxel alone.
Adverse Events
Regardless of prior chemotherapy, the most common adverse events in the elesclomol plus paclitaxel group included fatigue, alopecia, constipation, nausea, hypoaesthesia, arthralgia, insomnia, diarrhea and anemia. The most serious adverse events (Grade 3 or higher) for the combination arm were similar to those seen in the paclitaxel-only arm and included neutropenia, back pain, fatigue and neuropathy.
These data will be presented at the 44th Annual Meeting of the American Society of Clinical Oncology in Chicago in a poster entitled Phase II Trial of Elesclomol and Paclitaxel in Stage IV Metastatic Melanoma: A Subgroup Analysis By Prior Chemotherapy (Abstract # 9036).
Scientists Identify Factor Key To Severity Of Community-Associated Methicillin-Resistant Staph Infections
According to scientists led by Michael Otto, Ph.D., at the National Institute of Allergy and Infectious Diseases (NIAID), a key process that ensures the survival of S. aureus and causes severe disease involves members of the phenol-soluble modulin (PSM) protein family. The protein first attracts and then destroys protective human white blood cells in drug-resistant strains of the Staphylococcus aureus bacterium.
Their study describing how these proteins help determine disease severity and eliminate immune defense mechanisms against CA-MRSA was published online in "Nature Medicine,” by Dr. Otto and his colleagues at NIAID's Rocky Mountain Laboratories (RML).
Panton-Valentine Leukocidin
Up until a year ago, most scientists studying S. aureus believed they had narrowed their search for the cause of severe CA-MRSA infections, focusing on the Panton-Valentine leukocidin (PVL) toxin produced by certain strains. But then last year, Dr. Otto and his RML colleagues published a study indicating that PVL does not play a major role in CA-MRSA infections.
Role of PSM in Staphylococcus Infection
Dr. Otto's group continued its search to understand why the CA-MRSA strains cause widespread and often severe infections in otherwise healthy people. The RML group identified previously unknown PSMs secreted by S. aureus and identified the genes that encode those PSM proteins. They then compared PSM production between CA-MRSA and the most prominent hospital-associated MRSA strains. The research team found PSM genes in all MRSA strains, but production of the proteins was typically higher in CA-MRSA strains known for severe virulence, according to Dr. Otto.
Focus on Virulence
To determine whether PSMs contribute to virulence, the scientists developed test strains using the most widespread isolates of CA-MRSA, called USA300 and USA400. Each test strain had a certain combination of PSM-encoding genes removed so the researchers could ascertain whether those genes affected virulence.
The scientists then observed how laboratory mice responded to the test strains. By doing so, they pinpointed the "psm-alpha" gene cluster (which makes PSM-alpha protein) as playing an essential role in determining CA-MRSA virulence and, ultimately, disease severity.
To understand how PSMs contribute to virulence, Dr. Otto and colleagues next examined the role of the molecules in S. aureus evasion of human immune defenses. They observed that the "psm-alpha" genes generated the most resistance activity and the PSM-alpha proteins were best at destroying most immune cells that help protect against infection and disease. In all instances, the PSM-alpha molecules caused the greatest destruction of white blood cells, an effect that occurred rapidly.
Scientists ‘Reprogram’ Skin Cells into Stem Cells
In a breakthrough that could ease ethical issues related to the use of human embryos, two teams of scientists working separately believe they have created embryonic stem cells without having to make or destroy an embryo.
According to the research teams – one Japanese and one American from Wisconsin – this accomplishment involved the addition of four genes, which they say, reprogrammed the chromosomes of the skin cells, converting them into blank slates like embryonic cells, which should be able to turn into any of the 220 cell types of the human body.
The two independent teams maintain that their method also creates stem cells that genetically match the donor without cloning. If stem cells are used to make replacement cells and tissues for patients, it would be invaluable to have genetically matched cells because they would not be rejected by the immune system.
Even more important is that genetically matched cells from patients will enable scientist to study complex diseases, like Alzheimer’s, in the lab.
While both groups used just four genes to reprogram human skin cells, two of the four genes used by the Japanese scientists were different from two of the four used by the American group. All the genes in question, though, act in a similar way – they are master regulator genes whose role is to turn other genes on or off.
About 4 years ago, Dr. Shinya Yamanaka of Kyoto University and James Thomson of the University of Wisconsin-Madison, independently launched their respective searches for genes being used in an embryonic stem cell that are not being used in an adult cell to determine whether those genes would reprogram an adult cell.
Dr. Yamanaka worked with mouse cells, and Dr. Thomson worked with human cells from foreskins.
The researchers found more than 1,000 candidate genes. So both groups took educated guesses, trying to reduce the number of genes to the few dozen they thought might be the crucial ones and then questioning whether any combinations of those genes could turn a skin cell into a stem cell.
In Brief…
STIEFEL LABORATORIES, INC. ACQUIRES… ABR INVENT AND ABR DEVELOPMENT through a definitive stock purchase agreement. Stiefel plans to launch ABR’s Atlean dermal filler, which is currently commercialized in France and Italy, in multiple areas Atlean dermal filler in multiple areas, including parts of Europe, Asia Pacific, Latin America and the Caribbean. All sales representatives formerly employed by ABR Development will now become employees of Stiefel Laboratories.
Medimetriks Pharmaceuticals, Inc. … Begins Operations. The newly-formed Company, led by the founder and the key Senior Management Team of the former Bradley Pharmaceuticals will develop, license and commercialize innovative prescription products for the dermatology and podiatry marketplaces.
BARRIER THERAPEUTICS AND PROCTER & GAMBLE … AGREE to market Xolegel (ketoconazole, USP) Gel, 2% with Head & Shoulders Shampoo as Xolegel Duo The kit, which will be available by prescription in June, offers patients a complete treatment regimen for seborrheic dermatitis.
FDA Cleared
New Excimer Laser Cleared for Skin Dermatoses
FDA has granted 510K clearance to PhotoMedex’s XTRAC Velocity excimer laser system for the treatment of psoriasis, vitiligo, atopic dermatitis and leukoderma.
The XTRAC Velocity laser system delivers the highest UV power of any medical excimer laser available today, according to PhotoMedex, and does so with the same reliability and efficacy of its predecessor, the XTRAC Ultra.
The Velocity laser system is up to 3 times faster per treatment, according to company literature.
In February 2007, the BlueCross/BlueShield Association issued a national reference policy stating that targeted phototherapy (including the XTRAC) may be considered medically necessary for treating moderate to severe psoriasis comprising less than 20% body area for which narrow-band-UVB or psoralen plus UVA are indicated.
PhotoMedex developed the first FDA-approved laser treatment for psoriasis.
Birth Defects Associated with Mycophenolate Mofetil
New reports of serious congenital malformations, including microtia and cleft lip and palate, have emerged in infants whose mothers were exposed to mycophenolate mofetil (MMF) during pregnancy.
The active drug substance in CellCept, MMF, is an ester of the active metabolite mycophenolic acid (MPA), the active drug substance in Myfortic.
In most of the cases, the mothers were taking MMF following an organ transplant to prevent organ rejection. However, some mothers taking MMF were being treated for immune-mediated conditions such as systemic lupus erythematosus and erythema multiforme.
They were treated before becoming pregnant, and their treatments continued into the first trimester of their pregnancies or until the pregnancy was realized.
MMF and MPA increase the risk of spontaneous abortion in the first trimester and can cause congenital malformations in the offspring of women who are treated during pregnancy, and labeling for these drugs was revised in November 2007 when the pregnancy category was changed to “D” — positive evidence of human fetal risk. However, potential benefits may warrant use of the drug in pregnant women despite the potential risk.
FDA is continuing to work with the manufacturers of these drug products to develop and implement means to mitigate the risks of fetal exposure.
Clearance for Dual-Pulsed nd:YAG Laser
Lutronic has received FDA approval for its Spectra III multiple laser wavelength system. This dual-pulsed nd:YAG laser, the successor to the Spectra VERM II, removes epidermal and dermal pigmented lesions, including all types of tattoo colors.
Described as the most powerful laser in its class, according to the company, the Spectra III can be used for treating cosmetic and medical conditions for dermatologic and general surgical procedures involving coagulation and hemostasis.
New Type of Latex Cleared
The first device made from a new form of natural rubber latex has been cleared for marketing by the FDA.
Known as guayule latex, the material is derived from the guayule bush, which is found in the desert in the southeastern United States, to make the Yulex Patient Examination Glove (Yulex Corporation).
Traditional latex gloves are made from the milky sap of a rubber tree, Hevea braziliensis, and anywhere from 3% to 22% of all healthcare workers are sensitized to traditional latex. Available data on the new guayule latex show that even people who are highly allergic to traditional latex do not react on first exposure to guayule latex proteins.
Because there are no data on people’s long-term experience with the Yulex glove, the product will carry a warning for now about the potential for allergic reactions.
Other Drug News
Shingles Vaccine Recommended
The U.S. Centers for Disease Control and Prevention (CDC) is recommending that all appropriate people 60 years of age and older receive routine vaccination with a single dose of zoster vaccine line (Zostavax) to help prevent shingles. Zostavax is indicated for the prevention of herpes zoster (shingles) in people 60 years of age and older, and the vaccine has been included on the CDC’s 2007-2008 Recommended Adult Immunization Schedule.
The recommendations for vaccination include the following:
• People who report a previous episode of shingles and people with chronic medical conditions can be vaccinated — unless contraindications or precautions apply to their receiving Zostavax due to their conditions.
• Zostavax is not indicated for the treatment of shingles or postherpetic neuralgia (PHN), and the vaccine should not be to prevent people who have shingles from developing PHN.
• Healthcare providers do not need to ask patients about their history of varicella or conduct serologic tests for varicella immunity.
FDA Approvals & News
Scalp Psoriasis Treatment Approved
The FDA has approved the new drug application for calcipotriene 0.005% and betamethasone dipropionate 0.064% (Taclonex Scalp Topical Suspension). Taclonex Scalp is a topical suspension containing a combination of calcipotriene 0.005% and betamethasone dipropionate 0.064% for the treatment of moderate to severe psoriasis vulgaris of the scalp in adults.
BLA for Reloxin Accepted
The FDA has accepted the filing of a biologics license application for Reloxin, a botulinum toxin type A agent from Ipsen and Medicis. Reloxin is approved for aesthetic indications in 23 countries.
First Generic Calcipotriene Topical Solution
The FDA has granted approval for the first generic calcipotriene topical solution 0.005% (Scalp Solution). The product from
Fougera is in a formulation that compares to Dovonex by Warner-Chilcott.
Fougera’s Calcipotriene Topical Solution is indicated for the topical treatment of chronic, moderately severe psoriasis of the scalp, and it is available in a 60-ml bottle.
FDA Clearance for Skin Treatment Platform
The FDA granted clearance for Alma Laser’s Harmony (XL), a platform for aesthetic laser and light treatments.
The upgraded Harmony system combines lasers, pulsed light and near-infrared technologies. Multiple exchangeable handpieces enable treatment of more than 60 aesthetic indications and applications. These include acne, skin rejuvenation, hair removal, varicose veins, stretch marks, tattoo removal, wrinkles and skin tightening.
News & Trends
Product Mixup Prompts Medicis to Recall Solodyn
Medicis Pharmaceutical Corporation has announced a voluntary recall of lot numbers B080037 (Exp: 12/09) and B080038 (Exp: 12/09) of the antibiotic SOLODYN (minocycline HCl, USP) Extended Release Tablets, 90 mg, 30-count bottles (NDC 99207-461-30).
The announcement was made after Medicis received a report that one bottle in lot number B080037 contains AZASAN (azathioprine tablets) 75 mg (NDC 65649-231-51) instead of SOLODYN (minocycline HCl, USP) Extended Release Tablets, 90 mg. AZASAN, which is an immuno-suppressive agent used in transplant patients to prevent kidney rejection and for the treatment of rheumatoid arthritis, presents a potential health hazard and safety risk to patients. Side effects associated with the use of AZASAN, particularly in the elderly, include mylosuppression, infection, bleeding, chills, nausea, vomiting and diarrhea. Joint and muscle pain are also common side effects. Unanticipated interactions with other drugs may also lead to serious adverse events.
Any inquiries related to this recall should be addressed to Stericycle Customer Service at 1-888-656-6381 with representatives available Monday through Friday, 8 a.m. to 11 p.m. EST. For any medical information inquiries or to report an adverse event related to this recall, contact Medicis at 1-800-900-6389 with representatives available 24 hours a day, 7 days a week.
This recall is being conducted in cooperation with the contract manufacturer of the products and with the knowledge of the FDA.
Any adverse reactions experienced with the use of this product, and/or quality problems, also may be reported to the FDA's MedWatch Program by phone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, by mail at MedWatch, FDA, 5600 Fishers Lane, Rockville, MD 20852-9787, or on the MedWatch website at www.fda.gov/medwatch.
CDC Recommends Shingles Vaccine for Those Over Age 60
The U.S. Centers for Disease Control and Prevention has adopted the recommendation of its Advisory Committee on Immunization Practices calling for the use of Merk’s ZOSTAVAX, currently the only vaccine to prevent shingles, in adults aged 60 and older.
The ACIP recommendations call for routine vaccination with a single dose of this zoster vaccine for all appropriate candidates 60 years of age and older.
The recommendation targets people who have reported a previous episode of shingles in addition to those with chronic medical conditions for whom the vaccine is deemed safe. Vaccinees should be informed of the potential risk of transmitting the vaccine virus to varicella-susceptible individuals, including pregnant women who have not had chickenpox.
UK Scientists May Be Close to MRSA Cure
A British pharmaceutical has raised hopes of a cure for MRSA within 3 years.
Destiny Pharma presented this promising new drug as a nasal gel — initially to be known as XF-73 — for the first time at the annual European Conference of Clinical Microbiology and Infectious Diseases in Barcelona.
The new compound, which is is not yet approved by the National Institute for Clinical Excellence, is currently in trials. It works differently than anti-MRSA drugs that prevent the bacterium from growing and breeding in that it is designed to actually kill the microbes.
Trials
Five of the most common strains of MRSA were tested against the drug. A topical antibiotic was used as a control.
Both XF-73 and the antibiotic were separately exposed to the strains of MRSA 55 times, over as many days. Each time 99% of the bacteria were destroyed, leaving the strongest 1% to survive.
This was allowed to grow again before being exposed to the XF-73 and the control antibiotic. The scientists then measured how much of the drug was needed to kill the same amount of bacteria for each exposure.
In human trials, the compound is contained in a tiny amount of gel placed inside the nostril, which would prevent the spread of MRSA in hospitals and in the community. Company officials forsee the use of tablet and injection forms of XF-73 within a few years.
Hope for the Future
By 2011, XF-73 could be used to prevent the spread of infection in hospital wards, say researchers. Within 6 years, they claim, it could routinely cure patients already infected with MRSA.
Elesclomol Study Shows Significant Improvement in Progression-Free Survival for Chemotherapy-Naive Patients With Metastatic Melanoma
GlaxoSmithKline and Synta Pharmaceuticals Corp. announced positive Phase II clinical data for elesclomol (formerly STA-4783), an investigational agent currently in development for metastatic melanoma.
Chemotherapy-Naive Patients
A retrospective analysis showed that stage IV metastatic melanoma patients treated with elesclomol and paclitaxel who had not previously received chemotherapy had a statistically significant improvement in progression-free survival compared to patients who received paclitaxel alone.
This retrospective subgroup analysis of a randomized, double-blind, active-controlled, Phase II trial in patients with stage IV metastatic melanoma evaluated the rates of progression-free survival and overall survival for the combination of elesclomol and paclitaxel versus paclitaxel alone in patients who received one prior chemotherapy treatment with those who were chemotherapy-naive. A total of 81 patients evaluated in this analysis either received 213 mg/m2 of elesclomol co-infused with 80 mg/m2 paclitaxel or 80 mg/m2 of paclitaxel alone in 4-week cycles (once weekly for 3 weeks and 1 week's rest) until disease progression.
Patients who had not received prior chemotherapy and were given a combination of elesclomol and paclitaxel (n=24), compared to patients who were given paclitaxel alone (n=8).
Patients With Prior Chemotherapy
Data for patients on the elesclomol and paclitaxel arm who had one prior chemotherapy showed a trend toward results similar to patients who had received no prior chemotherapy; however these data were not statistically significant. Specifically, after receiving one prior chemotherapy, the median PFS was 2.8 months for patients receiving elesclomol and paclitaxel (n=29) versus 1.8 months for patients on paclitaxel alone (n=20; P=0.552), and OS was 9.0 months for patients on elesclomol and paclitaxel versus 7.8 months for patients on paclitaxel alone.
Adverse Events
Regardless of prior chemotherapy, the most common adverse events in the elesclomol plus paclitaxel group included fatigue, alopecia, constipation, nausea, hypoaesthesia, arthralgia, insomnia, diarrhea and anemia. The most serious adverse events (Grade 3 or higher) for the combination arm were similar to those seen in the paclitaxel-only arm and included neutropenia, back pain, fatigue and neuropathy.
These data will be presented at the 44th Annual Meeting of the American Society of Clinical Oncology in Chicago in a poster entitled Phase II Trial of Elesclomol and Paclitaxel in Stage IV Metastatic Melanoma: A Subgroup Analysis By Prior Chemotherapy (Abstract # 9036).
Scientists Identify Factor Key To Severity Of Community-Associated Methicillin-Resistant Staph Infections
According to scientists led by Michael Otto, Ph.D., at the National Institute of Allergy and Infectious Diseases (NIAID), a key process that ensures the survival of S. aureus and causes severe disease involves members of the phenol-soluble modulin (PSM) protein family. The protein first attracts and then destroys protective human white blood cells in drug-resistant strains of the Staphylococcus aureus bacterium.
Their study describing how these proteins help determine disease severity and eliminate immune defense mechanisms against CA-MRSA was published online in "Nature Medicine,” by Dr. Otto and his colleagues at NIAID's Rocky Mountain Laboratories (RML).
Panton-Valentine Leukocidin
Up until a year ago, most scientists studying S. aureus believed they had narrowed their search for the cause of severe CA-MRSA infections, focusing on the Panton-Valentine leukocidin (PVL) toxin produced by certain strains. But then last year, Dr. Otto and his RML colleagues published a study indicating that PVL does not play a major role in CA-MRSA infections.
Role of PSM in Staphylococcus Infection
Dr. Otto's group continued its search to understand why the CA-MRSA strains cause widespread and often severe infections in otherwise healthy people. The RML group identified previously unknown PSMs secreted by S. aureus and identified the genes that encode those PSM proteins. They then compared PSM production between CA-MRSA and the most prominent hospital-associated MRSA strains. The research team found PSM genes in all MRSA strains, but production of the proteins was typically higher in CA-MRSA strains known for severe virulence, according to Dr. Otto.
Focus on Virulence
To determine whether PSMs contribute to virulence, the scientists developed test strains using the most widespread isolates of CA-MRSA, called USA300 and USA400. Each test strain had a certain combination of PSM-encoding genes removed so the researchers could ascertain whether those genes affected virulence.
The scientists then observed how laboratory mice responded to the test strains. By doing so, they pinpointed the "psm-alpha" gene cluster (which makes PSM-alpha protein) as playing an essential role in determining CA-MRSA virulence and, ultimately, disease severity.
To understand how PSMs contribute to virulence, Dr. Otto and colleagues next examined the role of the molecules in S. aureus evasion of human immune defenses. They observed that the "psm-alpha" genes generated the most resistance activity and the PSM-alpha proteins were best at destroying most immune cells that help protect against infection and disease. In all instances, the PSM-alpha molecules caused the greatest destruction of white blood cells, an effect that occurred rapidly.
Scientists ‘Reprogram’ Skin Cells into Stem Cells
In a breakthrough that could ease ethical issues related to the use of human embryos, two teams of scientists working separately believe they have created embryonic stem cells without having to make or destroy an embryo.
According to the research teams – one Japanese and one American from Wisconsin – this accomplishment involved the addition of four genes, which they say, reprogrammed the chromosomes of the skin cells, converting them into blank slates like embryonic cells, which should be able to turn into any of the 220 cell types of the human body.
The two independent teams maintain that their method also creates stem cells that genetically match the donor without cloning. If stem cells are used to make replacement cells and tissues for patients, it would be invaluable to have genetically matched cells because they would not be rejected by the immune system.
Even more important is that genetically matched cells from patients will enable scientist to study complex diseases, like Alzheimer’s, in the lab.
While both groups used just four genes to reprogram human skin cells, two of the four genes used by the Japanese scientists were different from two of the four used by the American group. All the genes in question, though, act in a similar way – they are master regulator genes whose role is to turn other genes on or off.
About 4 years ago, Dr. Shinya Yamanaka of Kyoto University and James Thomson of the University of Wisconsin-Madison, independently launched their respective searches for genes being used in an embryonic stem cell that are not being used in an adult cell to determine whether those genes would reprogram an adult cell.
Dr. Yamanaka worked with mouse cells, and Dr. Thomson worked with human cells from foreskins.
The researchers found more than 1,000 candidate genes. So both groups took educated guesses, trying to reduce the number of genes to the few dozen they thought might be the crucial ones and then questioning whether any combinations of those genes could turn a skin cell into a stem cell.
In Brief…
STIEFEL LABORATORIES, INC. ACQUIRES… ABR INVENT AND ABR DEVELOPMENT through a definitive stock purchase agreement. Stiefel plans to launch ABR’s Atlean dermal filler, which is currently commercialized in France and Italy, in multiple areas Atlean dermal filler in multiple areas, including parts of Europe, Asia Pacific, Latin America and the Caribbean. All sales representatives formerly employed by ABR Development will now become employees of Stiefel Laboratories.
Medimetriks Pharmaceuticals, Inc. … Begins Operations. The newly-formed Company, led by the founder and the key Senior Management Team of the former Bradley Pharmaceuticals will develop, license and commercialize innovative prescription products for the dermatology and podiatry marketplaces.
BARRIER THERAPEUTICS AND PROCTER & GAMBLE … AGREE to market Xolegel (ketoconazole, USP) Gel, 2% with Head & Shoulders Shampoo as Xolegel Duo The kit, which will be available by prescription in June, offers patients a complete treatment regimen for seborrheic dermatitis.
FDA Cleared
New Excimer Laser Cleared for Skin Dermatoses
FDA has granted 510K clearance to PhotoMedex’s XTRAC Velocity excimer laser system for the treatment of psoriasis, vitiligo, atopic dermatitis and leukoderma.
The XTRAC Velocity laser system delivers the highest UV power of any medical excimer laser available today, according to PhotoMedex, and does so with the same reliability and efficacy of its predecessor, the XTRAC Ultra.
The Velocity laser system is up to 3 times faster per treatment, according to company literature.
In February 2007, the BlueCross/BlueShield Association issued a national reference policy stating that targeted phototherapy (including the XTRAC) may be considered medically necessary for treating moderate to severe psoriasis comprising less than 20% body area for which narrow-band-UVB or psoralen plus UVA are indicated.
PhotoMedex developed the first FDA-approved laser treatment for psoriasis.
Birth Defects Associated with Mycophenolate Mofetil
New reports of serious congenital malformations, including microtia and cleft lip and palate, have emerged in infants whose mothers were exposed to mycophenolate mofetil (MMF) during pregnancy.
The active drug substance in CellCept, MMF, is an ester of the active metabolite mycophenolic acid (MPA), the active drug substance in Myfortic.
In most of the cases, the mothers were taking MMF following an organ transplant to prevent organ rejection. However, some mothers taking MMF were being treated for immune-mediated conditions such as systemic lupus erythematosus and erythema multiforme.
They were treated before becoming pregnant, and their treatments continued into the first trimester of their pregnancies or until the pregnancy was realized.
MMF and MPA increase the risk of spontaneous abortion in the first trimester and can cause congenital malformations in the offspring of women who are treated during pregnancy, and labeling for these drugs was revised in November 2007 when the pregnancy category was changed to “D” — positive evidence of human fetal risk. However, potential benefits may warrant use of the drug in pregnant women despite the potential risk.
FDA is continuing to work with the manufacturers of these drug products to develop and implement means to mitigate the risks of fetal exposure.
Clearance for Dual-Pulsed nd:YAG Laser
Lutronic has received FDA approval for its Spectra III multiple laser wavelength system. This dual-pulsed nd:YAG laser, the successor to the Spectra VERM II, removes epidermal and dermal pigmented lesions, including all types of tattoo colors.
Described as the most powerful laser in its class, according to the company, the Spectra III can be used for treating cosmetic and medical conditions for dermatologic and general surgical procedures involving coagulation and hemostasis.
New Type of Latex Cleared
The first device made from a new form of natural rubber latex has been cleared for marketing by the FDA.
Known as guayule latex, the material is derived from the guayule bush, which is found in the desert in the southeastern United States, to make the Yulex Patient Examination Glove (Yulex Corporation).
Traditional latex gloves are made from the milky sap of a rubber tree, Hevea braziliensis, and anywhere from 3% to 22% of all healthcare workers are sensitized to traditional latex. Available data on the new guayule latex show that even people who are highly allergic to traditional latex do not react on first exposure to guayule latex proteins.
Because there are no data on people’s long-term experience with the Yulex glove, the product will carry a warning for now about the potential for allergic reactions.
Other Drug News
Shingles Vaccine Recommended
The U.S. Centers for Disease Control and Prevention (CDC) is recommending that all appropriate people 60 years of age and older receive routine vaccination with a single dose of zoster vaccine line (Zostavax) to help prevent shingles. Zostavax is indicated for the prevention of herpes zoster (shingles) in people 60 years of age and older, and the vaccine has been included on the CDC’s 2007-2008 Recommended Adult Immunization Schedule.
The recommendations for vaccination include the following:
• People who report a previous episode of shingles and people with chronic medical conditions can be vaccinated — unless contraindications or precautions apply to their receiving Zostavax due to their conditions.
• Zostavax is not indicated for the treatment of shingles or postherpetic neuralgia (PHN), and the vaccine should not be to prevent people who have shingles from developing PHN.
• Healthcare providers do not need to ask patients about their history of varicella or conduct serologic tests for varicella immunity.
