Thursday, January 25, 2018

Tapeworm drug could provide new hope for patients with Parkinson's disease

In continuation of Niclosamide
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Researchers at Cardiff University, in collaboration with the University of Dundee, have identified a drug molecule within a medicine used to treat tapeworm infections which could lead to new treatments for patients with Parkinson's disease.
Parkinson's disease is a long-term degenerative disorder of the central nervous system that, according to the charity, Parkinson's UK, affects one person in every 500. That means an estimated 127,000 people are currently living with Parkinson's disease in the UK alone.
Over the last decade or so, researchers striving to find a cure for this debilitating disease have focused their attention on a protein found in the human body known as PINK1. It's understood that the malfunction of this protein is one of the leading causes of Parkinson's disease.
Several studies have suggested that discovering a drug which is capable of enhancing the function of PINK1 could be a significant step in halting neurodegeneration and therefore slow down or even treat Parkinson's disease.
With this knowledge in mind, researchers at Cardiff and Dundee Universities have discovered that a drug traditionally used to treat tapeworm infections, named Niclosamide, is also an effective activator of the PINK1 protein.
Furthermore, the research, funded by The Welcome Trust, revealed that Niclosamide and some of its derivatives could enhance PINK1 performance within cells and neurons. This has given the researchers reason to believe that this drug could provide new hope for patients living with Parkinson's disease.
Dr Youcef Mehellou, from Cardiff University's School of Pharmacy and Pharmaceutical Sciences, who co-lead the study, said: 'This work represents the first report of a clinically used drug to activate PINK1 and may hold promise in treating Parkinson's disease. We will now take our findings to the next level by evaluating the ability of Niclosamide to treat Parkinson's disease in disease models. This is an exciting stage of our research and we are positive about the long term impact it could have on patients' lives."
Ref : http://www.cardiff.ac.uk/news/view/1027540-tapeworm-drug-could-lead-the-fight-against-parkinsons-disease

Wednesday, January 24, 2018

Anti-stress compounds provide new treatment approach for diabetes and obesity

For the first time, scientists from the Max Planck Institute of Psychiatry in Munich could prove that a stress protein found in muscle has a diabetes promoting effect. This finding could pave the way to a completely new treatment approach.
For some time, researchers have known that the protein FKBP51 is associated with depression and anxiety disorders. It is involved in the regulation of the stress system - when the system does not function properly; mental disorders may develop. Now, researchers at the Max Planck Institute of Psychiatry have discovered a new, surprising role for this protein: It acts as a molecular link between the stress regulatory system and metabolic processes in the body.
"FKBP51 influences a signaling cascade in muscle tissue, which with excessive calorie intake leads to the development of glucose intolerance, i.e., the key indicator of diabetes type 2," project leader Mathias Schmidt summarizes. An unhealthy diet, rich in fat means stress for the body. If FKBP51 is increasingly produced in the muscle it leads to reduced absorption of glucose - as a result, diabetes and obesity may develop.
If FKBP51 is blocked, diabetes will not develop, even if too many calories are consumed or the body is still stressed. Less FKBP51 in the muscle tissue means reduced glucose intolerance and thus maintenance of normal metabolism.
Antagonist provides novel treatment approach
The protein FKBP51 can be pharmacologically blocked by antagonist compounds that were developed at the Max Planck Institute by Felix Hausch (presently at University of Darmstadt). In collaboration with the scientists at the Technical University Darmstadt and funded by the Bavarian State Ministry of Economic Affairs and Media, Energy and Technology, these compounds will be further developed for use in clinical trials. "These findings may provide a completely new treatment approach for diabetes and other metabolic diseases," states Alon Chen, Director at the Max Planck Institute of Psychiatry.​
Ref : https://www.mpg.de/11850791/diabetes-fkbp511


Tuesday, January 23, 2018

Study: Ketamine more effective than common sedative in reducing suicidal thoughts

In continuation of my update on ketamine
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Ketamine was significantly more effective than a commonly used sedative in reducing suicidal thoughts in depressed patients, according to researchers at Columbia University Medical Center (CUMC). They also found that ketamine's anti-suicidal effects occurred within hours after its administration.
The findings were published online last week in the American Journal of Psychiatry.
According to the Centers for Disease Control and Prevention, suicide rates in the U.S. increased by 26.5 percent between 1999 and 2015.
"There is a critical window in which depressed patients who are suicidal need rapid relief to prevent self-harm," said Michael Grunebaum, MD, a research psychiatrist at CUMC, who led the study. "Currently available antidepressants can be effective in reducing suicidal thoughts in patients with depression, but they can take weeks to have an effect. Suicidal, depressed patients need treatments that are rapidly effective in reducing suicidal thoughts when they are at highest risk. Currently, there is no such treatment for rapid relief of suicidal thoughts in depressed patients."
Most antidepressant trials have excluded patients with suicidal thoughts and behavior, limiting data on the effectiveness of antidepressants in this population. However, previous studies have shown that low doses of ketamine, an anesthetic drug, causes a rapid reduction in depression symptoms and may be accompanied by a decrease in suicidal thoughts.
The 80 depressed adults with clinically significant suicidal thoughts who enrolled in this study were randomly assigned to receive an infusion of low-dose ketamine or midazolam, a sedative. Within 24 hours, the ketamine group had a clinically significant reduction in suicidal thoughts that was greater than with the midazolam group. The improvement in suicidal thoughts and depression in the ketamine group appeared to persist for up to six weeks.
Those in the ketamine group also had greater improvement in overall mood, depression, and fatigue compared with the midazolam group. Ketamine's effect on depression accounted for approximately one-third of its effect on suicidal thoughts, suggesting the treatment has a specific anti-suicidal effect.
Side effects, mainly dissociation (feeling spacey) and an increase in blood pressure during the infusion, were mild to moderate and typically resolved within minutes to hours after receiving ketamine.
"This study shows that ketamine offers promise as a rapidly acting treatment for reducing suicidal thoughts in patients with depression," said Dr. Grunebaum. "Additional research to evaluate ketamine's antidepressant and anti-suicidal effects may pave the way for the development of new antidepressant medications that are faster acting and have the potential to help individuals who do not respond to currently available treatments."

Monday, January 22, 2018

Drug used to prevent and treat malaria may also be effective for Zika virus

In continuation of my update on chloroquine
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A new collaborative study led by researchers at Sanford Burnham Prebys Medical Discovery Institute (SBP) and UC San Diego School of Medicine has found that a medication used to prevent and treat malaria may also be effective for Zika virus. The drug, called chloroquine, has a long history of safe use during pregnancy, and is relatively inexpensive. The research was published today in Scientific Reports.
Zika virus remains a major global health risk. In most adults, Zika causes mild flu-like symptoms. But in pregnant women, the virus can cause serious birth defects in babies--including microcephaly--a neurological condition in which newborns have unusually small heads and fail to develop properly. There is no treatment or way to reverse the condition.
"There is still an urgent need to bolster our preparedness and capacity to respond to the next Zika outbreak," says Alexey Terskikh, Ph.D., associate professor at SBP. "Our latest research suggests the anti-malaria drug chloroquine may be an effective drug to treat and prevent Zika infections."
Terskikh is co-senior author of a new study that examined the effect of chloroquine in human brain organoids and pregnant mice infected with the virus, and found the drug markedly reduced the amount of Zika virus in maternal blood and neural progenitor cells in the fetal brain. Pregnant mice received chloroquine through drinking water in dosages equivalent to acceptable levels used in humans.
"Our research is the first to study Zika infection in a mouse model that transmits the virus in a way similar to humans," explains Alysson R. Muotri, Ph.D., professor and director of the Stem Cell Program at UC San Diego and co-senior author of the study. "Until now, researchers used a mouse strain that is deficient in interferon--a signaling protein that heightens anti-viral defenses. Those mice actually die from Zika infection, making it difficult to study the natural transmission of the virus from father and mother to fetus and to assess the effect of this transmission on the newborns.
"We believe our mouse model more accurately represents the way Zika virus infects men, women, and babies while in the womb," adds Terskikh. "Although chloroquine didn't completely clear Zika from infected mice it did reduce the viral load, suggesting it could limit the neurological damage found in newborns infected by the virus."
"In the 1950's, the Brazilian health agencies added chloroquine into cooking salt and distributed it to the population in endemic areas as an effective way of spreading the inexpensive anti-malarial drug as a prophylactic on a wide scale. This strategy was known as Pinotti's Method, named after its originator Dr. Mario Pinotti. It might be worth considering this medicated salt program one more time in Brazil", suggests Muotri.
"Chloroquine has a long history of successfully treating malaria, and there are no reports of it causing birth defects," says Terskikh. "Additional studies are certainly needed to determine the precise details of how it works. But given its low cost, availability and safety history further study in a clinical trial to test its effectiveness against Zika virus in humans is merited."
Ref : http://www.newswise.com/articles/view/685239/

Friday, January 19, 2018

Dr. Reddy’s Announces Approval of Impoyz (clobetasol propionate) Cream for Plaque Psoriasis

Dr. Reddy’s Laboratories Ltd. through its wholly owned subsidiary Promius Pharma, LLC, announced its fifth consecutive, first-cycle NDA approval for the Proprietary Products Group, a substantial milestone within the pharmaceutical industry.
Impoyz (clobetasol propionate) Cream, 0.025% is a high potency topical steroid approved for the treatment of moderate to severe plaque psoriasis in patients 18 years of age or older. The most common side effect of Impoyz Cream includes discoloration of the treated site. Psoriasis is a serious medical condition affecting approximately 7.5 million people in the United States. Impoyz, formerly referred to as DFD-06, had been recently licensed to Encore Dermatology Inc. for the commercialization of the product in the United States.

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This approval is another example of the deep and broad capabilities within the Proprietary Products business unit at Dr. Reddy’s. The organization has achieved several milestones within drug, device, and formulation research and development for novel therapies.
“The fifth consecutive first cycle NDA approval represents Dr. Reddy’s long-term commitment to building an organization that delivers innovative medical solutions,” said Anil Namboodiripad, PhD, Senior Vice President, Proprietary Products and President, Promius Pharma. “We are looking forward to working with our partner, Encore Dermatology, to bring this novel treatment to providers and their patients.”
“Encore is excited about adding another great product to our portfolio and looking forward to the opportunity to commercialize a new product for the treatment of mild to moderate psoriasis as well as broadening our portfolio outside of atopic dermatitis and acne,” said Robert Moccia, CEO, Encore Dermatology, Inc.

Thursday, January 18, 2018

Trial shows apple allergen as effective treatment option for birch pollen-related apple allergy

In continuation of my update on Osimertinib

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Osimertinib improves progression-free survival compared to standard first line therapy in Asian patients with EGFR-mutated non-small-cell lung cancer (NSCLC), according to the Asian subset analysis of the FLAURA trial presented at the ESMO Asia 2017 Congress, sumultaneously published in The New England Journal of Medicine.
EGFR mutations occur in 30-40% of NSCLC in Asian populations compared to 10-15% in Western populations. The phase III FLAURA trial compared osimertinib, a third generation EGFR-tyrosine kinase inhibitor (TKI), to standard of care EGFR-TKIs (erlotinib or gefitinib) as first line therapy in NSCLC patients with EGFR mutations. A total of 556 patients from Asia, Europe, and North America were randomized 1:1 to treatment with osimertinib or standard of care. Osimertinib improved progression-free survival by 54%.
This subset analysis included the 322 Asian patients in the FLAURA trial, of whom 46 were Chinese, 120 were Japanese, and 156 were from other parts of Asia.
The median progression-free survival was 16.5 months with osimertinib compared to 11.0 months for the standard therapy, with a hazard ratio of 0.54 (95% confidence interval, 0.41-0.72; p<0.0001).
The median duration of response was two-fold higher for patients treated with osimertinib (17.6 months) compared to standard of care (8.7 months). The overall response rate was 80% with osimertinib compared to 75% with standard of care treatment. Median overall survival was not reached. The incidence of grade 3 or higher toxicities was lower for osimertinib (40%) than the standard treatment (48%).
Lead author Professor Byoung Chul Cho, Yonsei Cancer Center, Seoul, Korea, said: "As in the overall trial population, osimertinib provided a significant progression-free survival benefit in Asian patients with EGFR-mutated NSCLC. Asian patients had similar toxicities with osimertinib as the overall FLAURA population. Osimertinib should be the preferred first line treatment for EGFR-mutant NSCLC in Asia."
Commenting on the findings Professor James CH Yang, Chairman, Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei City, Taiwan, said: "The results of this subset analysis are quite compatible with the findings in the overall population presented at the ESMO 2017 Congress in Madrid. We can therefore conclude that osimertinib can be considered as the standard of care for the first line treatment of Asian advanced NSCLC patients with EGFR mutations."
"The proportion of patients having adverse events that caused them to stop taking osimertinib was similar in the overall (13%) and Asian (15%) populations," added Yang. "We tend to think osimertinib is a well tolerated drug so these discontinuation rates were surprisingly high and need further investigation."
Yang continued: "Although there was no statistical difference between the hazard ratios for progression-free survival, it was numerically lower in non-Asians (0.34) compared to Asians (0.54). There is an ongoing debate as to whether Asian and non-Asian patients with EGFR mutations have distinct responses to EGFR-TKIs. This might be due to variations in clinical practice rather than biology. A meta-analysis of all relevant studies could shed light on this issue."
"It will also be important to know whether Asian and non-Asian patients in the FLAURA trial with brain metastases had similar outcomes," said Yang.

Tuesday, January 16, 2018

Soy foods, cruciferous vegetables may reduce breast cancer treatment’s side effects

In continuation of my update on soy milk
Consuming soy foods (such as soy milk, tofu and edamame) and cruciferous vegetables (such as cabbages, kale, collard greens, bok choy, Brussels sprouts, and broccoli) may be associated with a reduction in common side effects of breast cancer treatment in breast cancer survivors, say a team of scientists led by Georgetown Lombardi Comprehensive Cancer Center.
In the study, published in Breast Cancer Research and Treatment, higher intake of cruciferous vegetables and soy foods were associated with fewer reports of menopausal symptoms. Higher soy intake was also associated with less reported fatigue. The breast cancer survivors studied included 173 non-Hispanic white and 192 Chinese Americans including US-born Chinese and Chinese immigrants.
Researchers say breast cancer survivors often experience side effects from cancer treatments that can persist months or years after completion of treatment. For example, because many treatments designed to prevent breast cancer recurrence inhibit the body's production or use of estrogen, the hormone that can fuel breast cancer growth, breast cancer patients often experience hot flashes and night sweats, among other side effects.
The lead author on the study, Sarah Oppeneer Nomura, PhD, of Georgetown Lombardi, said that while further research is needed in larger study populations and with more detailed dietary data, this project addresses an important gap in research on the possible role of lifestyle factors, such as dietary habits, in relation to side effects of treatments.
"These symptoms can adversely impact survivors' quality of life and can lead them to stopping ongoing treatments, she says. "Understanding the role of life style factors is important because diet can serve as a modifiable target for possibly reducing symptoms among breast cancer survivors."
When study participants were evaluated separately by race/ethnicity, associations were significant among white breast cancer survivors; however; while a trend was seen in the benefit for Chinese women, results were not statically significant. Researchers explain Chinese women typically report fewer menopausal symptoms. Most of them also consume cruciferous vegetables and soy foods, making it difficult to see a significant effect in this subgroup. Indeed, in this study, Chinese breast cancer survivors ate more than twice as much soy and cruciferous vegetables.
Whether the reduction in symptoms accounts for longtime use of soy and cruciferous vegetables needs further investigation, says the study's senior author, Judy Huei-yu Wang, PhD, of Georgetown Lombardi's Cancer Prevention and Control Program.
Results obtained in preclinical studies in animals show that biologically active compounds present in both soy and cruciferous vegetables cause breast cancer cells to grow, but have opposite effects in animals that consume these compounds well before cancer is diagnosed and continue consuming them during and after cancer treatments.
Until more research is conducted, breast cancer patients should not suddenly start eating soy, if they have not consumed it before, says Leena Hilakivi-Clarke, PhD, a professor of oncology at Georgetown Lombardi and a co-author of the study.
Researchers also found suggestive associations with lower reporting of other symptoms, including joint problems, hair thinning/loss and memory less in women who consumed more soy foods, but these associations did not reach statistical significance.
Phytochemicals, or bioactive food components, such as isoflavones in soy foods and glucosinolates in cruciferous vegetables may be the source of the benefit, researchers say. Isoflavones bind to estrogen receptors and exert weak estrogenic effects, among other effects. Glucosinolates in cruciferous vegetables influence levels of metabolizing enzymes that can modulate inflammation and levels of estrogen, possibly attenuating treatment-related symptoms.

Monday, January 15, 2018

Novel compound along with checkpoint inhibitors may enhance immune response in melanoma patients

A novel compound may restore immune response in patients with melanoma, according to a study presented at the ESMO Immuno Oncology Congress 2017.
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"Checkpoint inhibitors are a standard of care immunotherapy for metastatic melanoma," said lead author Dr Sapna Patel, Assistant Professor, Department of Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, US. "However, many patients do not respond because myeloid derived suppressor cells (MDSCs), a type of inhibitory cell, are present in the tumor microenvironment."
"In animal studies, omaveloxolone inhibited MDSCs and restored immune activity," she continued. "Myeloid-derived suppressor cells (MDSCs) produce reactive nitrogen radicals that alter the receptors on the surface of the tumor to hide it from cytotoxic lymphocytes that kill tumor cells. Omaveloxolone inhibits MDSC activity, suppresses reactive nitrogen radicals, and restores anti-tumor immune responses. Administering omaveloxolone with checkpoint inhibitors may improve the antitumor response of these immunotherapies."
This open label, multicenter, phase 1B trial investigated the safety and efficacy of omaveloxolone in combination with the checkpoint inhibitors ipilimumab or nivolumab. The study included 30 patients with unresectable or metastatic melanoma, of whom seven were naïve to checkpoint inhibitors and 23 had prior checkpoint inhibitor treatment.
The overall response rate was 57% in checkpoint inhibitor naïve patients and 17% in those with prior exposure. Median time to response was 19 weeks. There were no serious adverse events related to omaveloxolone and it was well tolerated in combination with ipilimumab or nivolumab.
Dr Patel said: "Our findings suggest that omaveloxolone may overcome resistance to checkpoint inhibitors. Omaveloxolone in combination with checkpoint blockade had activity in both naïve and checkpoint inhibitor refractory melanoma patients."
She added: "This is one of the first studies to demonstrate a meaningful response rate in the checkpoint inhibitor refractory melanoma population. Further dose escalation and dose expansion studies are underway as well as translational tissue-based experiments to clarify the impact of this treatment combination."
Commenting on the study for ESMO, Dr Olivier Michielin, head of Personalised Analytical Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland, said: "Omaveloxolone's novel mechanism of action is to block MDSCs, cells known to suppress the immune response. This study tested a new combination therapy in immuno oncology and found encouraging response rates with omaveloxolone plus ipilimumab or nivolumab in patients who were checkpoint inhibitor naïve or resistant. The combination was well tolerated and may address some of the immune escape mechanisms that limit the activity of current checkpoint blockade therapies."
Michielin added: "More data is needed before we can make a final call on whether there is a place, and where would the place be, for this combination in the current treatment portfolio. The next step should be a randomized trial to investigate whether omaveloxolone provides additional benefit when combined with the checkpoint blockade backbone, for example, comparing the efficacy of PD-1 blockade alone versus PD-1 blockade plus omaveloxolone."

Friday, January 12, 2018

Drug improves disease-free, overall survival after hematopoietic stem cell transplants

In continuation of my update on Abatacept (Orencia)
Results from a phase 2 clinical trial, presented by Seattle Children's Research Institute at the 59th American Society of Hematology (ASH) Annual Meeting, show that the drug Abatacept (Orencia) nearly eliminated life-threatening severe acute graft-versus-host disease (GvHD) in patients receiving hematopoietic stem cell transplants.
Abatacept, when added to the standard drug regimen used to prevent GvHD, reduced the occurrence of acute, grade III-IV GvHD from 32 to 3 percent in pediatric and adult patients who underwent mismatched unrelated donor stem cell transplants to treat advanced cancer and other blood disorders. As a result, patients receiving the post-transplant regimen with abatacept experienced improved disease-free and overall survival compared to those who did not.
Acute GvHD is the most deadly complication that can arise after stem cell transplantation. Graft-versus-host disease occurs when the donated T cells, white blood cells in the immune system that fight infection, launch a vigorous attack on a patient's organs, including the skin, liver, kidneys, lung, and the gastrointestinal tract. For patients receiving cells from an unrelated donor, the rate of mild-to-severe forms of acute GvHD can reach as high as 80 percent, with up to half of patients dying from the most severe forms.
"Given the serious threat of graft-versus-host disease, new approaches to make stem cell transplants safer for patients remain a critical unmet need," said Dr. Leslie Kean, the trial's principal investigator and associate director of the Ben Towne Center for Childhood Cancer Research at Seattle Children's. "To see such striking results in patients at extremely high risk for graft-versus-disease is incredibly encouraging."
Kean first became interested in using abatacept to prevent GvHD based on the immunotherapy drug's success in treating patients with rheumatoid arthritis. In rheumatoid arthritis, abatacept inhibits T-cell activation and prevents the chain of events that lead to debilitating joint inflammation.
Similarly, feasibility studies conducted by Kean found that abatacept blocks the activation of certain T cells after transplant. In their models, abatacept reduced the proliferation and activation of effector T cells. Effector T cells incite GvHD when they become overactive as the patient's immune system starts to rebuild itself from the donor stem cells.
"Preventing graft-versus-host disease and relapse after transplant requires a difficult balance of eliminating the bad, overactive effector T cells, without suppressing the good, regulatory T cells," said Kean, who is also an associate professor of pediatrics at the University of Washington School of Medicine and a member of the Fred Hutchinson Cancer Research Center. "As we make improvements to our toolbox of agents capable of achieving this Holy Grail of stem cell transplant, it's essential to include targeted approaches like abatacept."
The multicenter data presented included two patients cohorts who were enrolled across 18 sites. In the cohort of patients who received transplants from mismatched unrelated donors, all 43 patients received four doses of abatacept with a calcineurin inhibitor and methotrexate. To serve as the control, researchers looked at data from a national database of matched patients receiving two commonly used regimens to prevent GvHD - a calcineurin inhibitor and methotrexate (CNI/MTX) or a calcineurin inhibitor and methotrexate plus anti-thymocyte globulin (+ATG).
At 100 days post-transplant, the cumulative incidence of grade III-IV acute GvHD occurred in 3 percent of patients receiving abatacept compared to 32 percent receiving CNI/MTX and 22 percent receiving +ATG. Patients receiving abatacept had intact immune reconstitution, significant improvement in transplantation-related mortality, no major uncontrolled infection and no increase in disease relapse. Significant survival advantages for the abatacept group were demonstrated at one year post-transplant. Overall survival improved to 85 percent (vs. 57 percent in CNI/MTX and 68 percent in +ATG controls); 79 percent of patients experienced disease-free survival (vs. 50 percent in CNI/MTX and 63 percent in +ATG controls).
The second cohort of 140 patients with human leukocyte antigen-matched unrelated donor transplants completed enrollment in November 2017, with data expected from this randomized double-blind arm of the study in the next six months.
"As a transplant physician, it's beyond heartbreaking to witness a patient develop severe acute graft-versus-host disease after having their leukemia cured through bone marrow transplant," said Kean. "To have a therapy at our disposal that safely targets just the T cells causing graft-versus-host disease would represent a major step forward in stem cell transplantation. It not only offers new hope that we can prevent graft-versus-host disease upfront, but that we can also significantly improve outcomes for patients requiring high-risk transplants."

Thursday, January 11, 2018

Ortho Dermatologics Announces U.S. FDA Filing Acceptance For IDP-118, Novel Plaque Psoriasis Treatment

Ortho Dermatologics, a division of Valeant Pharmaceuticals International, Inc. (NYSE: VRX and TSX: VRX), today announced that the U.S. Food and Drug Administration (FDA) has accepted the New Drug Application (NDA) for IDP-118 (halobetasol propionate and tazarotene) lotion, an investigational topical treatment for plaque psoriasis. The PDUFA action date is June 18, 2018.
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If approved, IDP-118 will be the first and only topical lotion that contains a unique combination of halobetasol propionate and tazarotene in one formulation for the treatment of plaque psoriasis in adult patients, allowing for a potentially expanded duration of use.
The most common adverse events were contact dermatitis (7.4%) and application site pain (2.6%)...