Cancer fighting effects of aspirin revealed in bowel tumor study

Researchers have shed light on how taking aspirin can help to stave off bowel cancer.

Experts found that the painkiller blocks a key process linked to tumour formation.

Regular use of aspirin is known to reduce a person's risk of developing colon cancer but the drug's tumour fighting properties have not been well understood.

Researchers at the University of Edinburgh focused on a structure found inside cells called the nucleolus.

Activation of the nucleolus is known to drive tumour formation and dysfunction has also been linked to Alzheimer's and Parkinson's.

The team at the University's Cancer Research UK Edinburgh Centre tested the effects of aspirin on cells grown in the lab and on tumour biopsies removed from colon cancer patients.

They found that aspirin blocks a key molecule called TIF-IA, which is essential for the nucleolus to function.

Not all colon cancer patients respond to aspirin but the researchers say their findings could help pinpoint those most likely to benefit.

Aspirin has side effects that include internal bleeding and it can cause certain types of stroke. Long term use is not recommended. The researchers say the study paves the way for the development of new, safer therapies that mimic aspirin's effects.

The research, published in Nucleic Acids Research, was funded by the Medical Research Council and the Biotechnology and Biological Sciences Research Council. Worldwide Cancer Research, Bowel and Cancer Research and The Rosetrees Trust also supported the work.

Dr. Lesley Stark, of the Cancer Research UK Edinburgh Centre at the University of Edinburgh, said: "We are really excited by these findings as they suggest a mechanism by which aspirin may act to prevent multiple diseases. A better understanding of howaspirin blocks TIF-IA and nucleolar activity provides great promise for the development of new treatments and targeted therapy."

Experimental drug restores some bladder function after spinal cord injury, study finds

An experimental drug that blocks abnormal neural communication after spinal cord injury could one day be the key to improving quality of life by improving bladder function, new research suggests.

Researchers at The Ohio State University tested the drug—which is currently available only for research—to gauge its potential to improve bladder function after spinal cord injury in mice and saw promising results.

The experimental drug (LM11A-31) appears to help by blocking the dual activity of pro-nerve growth factor (proNGF) and a receptor called p75. ProNGF is known to be secreted from the cell after nerve injury.

After a month-long treatment after spinal cord injury in mice, bladder volume decreased significantly to a level close to normal, said lead researcher Sung Ok Yoon, an associate professor of biological chemistry and pharmacology at Ohio State.

The study appears in The Journal of Clinical Investigation.

In humans, spinal cord injuries sever the communication between the bladder and the brain, leading to the loss of the normal ability to urinate at will. This leads to bladder over-filling, which causes high pressure and bladder enlargement due to thickening of the muscular bladder walls. This can cause urine to return to the kidney, which can lead to kidney infection and disease, Yoon said.

People with spinal cord injury typically rely on a catheter to pass urine.

Eventually, Yoon said, a new circuit of nervous-system communication is formed within the spinal cord, and it allows urine to be expelled unexpectedly, causing incontinence.

"There are no approved medications to treat bladder dysfunction brought on by spinal cord injuries, something that is a major concern and diminishes quality of life for these patients," Yoon said."This drug appears to help maintain near-normal bladder pressure and less unexpected expulsion of urine in mice."

Because the experimental drug does not restore normal communication between the bladder and the brain, it is certainly not a cure, Yoon said. Based on the mouse study, however, patients are likely to experience reduced bladder volume, which would lower the risk of bladder infection and reflux to the kidney, and less incontinence.

"The structure as well as the integrity of the neural communication in the bladder is expected to improve as well, contributing to the overall health of the bladder," she said.

Yoon and her collaborators also confirmed—through samples from two recent spinal-cord injury patients—the presence of proNGF in the urine within hours after injury. Urine from healthy people does not contain the growth factor. Yoon said that since the drug counteracts proNGF action, these findings could potentially be extended to further research into other types of bladder dysfunction besides spinal cord injury.

https://www.jci.org/articles/view/97837

Ref : https://www.jci.org/

Spironolactone may be an alternative to antibiotics in women's acne treatment

In continuation of my update on spironolactone

In a finding that suggests the potential for practice change that would reduce the use of antibiotics in dermatology, researchers in the Perelman School of Medicine at the University of Pennsylvania have found the diuretic drug spironolactone may be just as effective as antibiotics for the treatment of women's acne. The study, published this month in the Journal of Drugs and Dermatology, found patients who were originally prescribed spironolactone changed to a different drug within one year at almost the same rate as those who were prescribed antibiotics. The prescription change is a proxy for ineffectiveness, since switching is often the result of treatment failure due to lack of efficacy, side effects, cost, or other factors.

Acne is one of the most common diseases in the world. It affects 85 percent of people under the age of 18, but it also regularly impacts adults. More than 50 percent of women in the United States are treated for acne between the ages of 20 and 29, while more than 35 percent are treated between the ages of 30 and 39.

Oral antibiotics are the most common systemic treatment for acne, and when combined with the large patient population, the result is that dermatologists prescribe the highest level of antibiotics per provider among all medical specialties, according to the Centers for Disease Control—a fact that contributes to concerns about increased resistance to antibiotics across all fields of medicine.

"It's clear that a safe alternative to oral antibiotics could have a huge benefit, and our data show spironolactone may be that alternative," said the study's lead author John S. Barbieri, MD, MBA, Dermatology chief resident at Penn. David J. Margolis, MD, Ph.D., a professor of Dermatology, was the study's senior author.

Spironolactone, marketed under the name aldactone, is currently approved to treat high blood pressure, heart failure, and conditions that cause people to retain fluid. It blocks the effects of male hormones like androgen, meaning it's not an option to treat acne in men. However, those same anti-hormonal effects can help prevent acne outbreaks in women. As a result, some dermatologists use it to treat female acne patients.

Researchers compared data on 6,684 women and girls taking spironolactone to 31,614 who were prescribed antibiotics. Within a year, 14.4 percent of spironolactone patients and 13.4 percent of antibiotic patients had switched to alternative treatments, suggesting each treatment was working at almost the same rate, despite the fact that tetracycline-class antibiotics are prescribed five times as frequently.

"These numbers suggest dermatologists should consider spironolactone first instead of antibiotics when it comes to women with acne," Barbieri said.

In addition to the benefits for antibiotic stewardship, Barbieri pointed to several studies showing long-term oral antibiotic use may be associated with antibiotic resistance, lupus, inflammatory bowel disease, and even colon and breast cancer.

"This indicates spironolactone may have a better safety profile than oral antibiotics, which is another factor that makes it such an appealing option," Barbieri said. He also noted spironolactone is less expensive, which may be relevant to patients with high deductibles or who are uninsured.

Spironolactone is not approved for the treatment of acne by the U.S. Food and Drug Administration despite expert opinion supporting its use, and Barbieri says the findings of this study should be confirmed by a randomized controlled trial that directly compares the two treatment options.

FDA Advisory Committee Recommends the Approval of Baricitinib 2mg, but not 4mg, for the Treatment of Moderately-to-Severely Active Rheumatoid Arthritis

Eli Lilly and Company (NYSE: LLY) and Incyte Corporation (NASDAQ: INCY) announced  that the U.S. Food and Drug Administration's (FDA) Arthritis Advisory Committee recommended approval of the 2-mg dose of baricitinib, a once-daily oral medication for the treatment of moderately-to-severely active rheumatoid arthritis (RA) for adult patients who have had an inadequate response or intolerance to methotrexate. While the Advisory Committee unanimously supported the efficacy of the 4-mg dose of baricitinib, it did not recommend approval of the 4-mg dose of baricitinib for the proposed indication based on the adequacy of the safety and benefit-risk profiles.

"We are confident that baricitinib, if approved, can help people in the U.S. manage the challenges of living with RA," said Christi Shaw, president of Lilly Bio-Medicines. "While we are disappointed with the Advisory Committee's assessment of the data for the 4-mg dose, we are confident in the positive benefit-risk profile of both the 2-mg and the 4-mg doses. We look forward to continuing our work with the FDA on our New Drug Application (NDA) and are hopeful that baricitinib will receive approval in the coming months."

Baricitinib 2-mg and 4-mg doses are approved in more than 40 countries, including the member states of the European Union and Japan.

For both doses, the Advisory Committee voted to support the assessment that baricitinib's data provide substantial evidence of efficacy. For the 2-mg dose, the Advisory Committee voted in favor of the assessment that baricitinib's safety data adequately support its approval. For the 4-mg dose, the Advisory Committee voted against the assessment that baricitinib's safety data was adequate to support its approval based on the proposed indication.

The Advisory Committee's recommendation was based on baricitinib's global development program, which included four completed Phase 3 studies. In total, 3,492 patients, who represented a range of treatment experiences, received baricitinib in the global RA development program. The Phase 3 studies evaluated baricitinib's treatment impact related to RA signs and symptoms, physical function, joint damage progression and other patient-reported outcomes. The Phase 3 program also evaluated recognized risks for RA patients, including serious infection, malignancy, major adverse cardiovascular events (MACE), venous thromboembolism (VTE), and gastrointestinal perforations, along with key laboratory changes. The safety profile of baricitinib is based on 7,860 patient-years of exposure.

"Despite advances in the management of RA over the last 20 years, which include early treatment, optimized use of traditional therapies for rheumatic disease and the advent of newer medications such as biologics, many patients are still struggling to meet treatment targets, and live with debilitating pain, fatigue and other symptoms of RA," said Peter Taylor, MA, PhD, professor, University of Oxford, an expert who attended the Advisory Committee Meeting. "Baricitinib could be a promising option for RA patients in the U.S. who are not achieving adequate disease control with currently available treatments."

The FDA is not required to follow the Advisory Committee's recommendation, but will consider it during its review of the NDA for baricitinib.

FDA Advisory Committee Recommends the Approval of Baricitinib 2mg, but not 4mg, for the Treatment of Moderately-to-Severely Active Rheumatoid Arthritis

Alkermes Announces FDA Acceptance for Review of New Drug Application for ALKS 5461 for the Adjunctive Treatment of Major Depressive Disorder

In continuation of my update on ALKS-5461  .................

We know that, Buprenorphine/samidorphan (developmental code name ALKS-5461) is a combination drug formulation of buprenorphine and samidorphan acting as a μ-opioid receptor antagonist which is under development by Alkermes as an adjunct to antidepressant therapy in treatment-resistant depression (TRD).

Buprenorphine 

 Samidorphan

Alkermes plc (Nasdaq: ALKS)announced that the U.S. Food and Drug Administration (FDA) has accepted for review the New Drug Application (NDA) for ALKS 5461, a novel, once-daily, oral investigational medicine for the adjunctive treatment of major depressive disorder (MDD) in patients with an inadequate response to standard antidepressant therapies. FDA's target action date for the ALKS 5461 NDA is Jan. 31, 2019.

FDA's acceptance of the ALKS 5461 NDA and rescission of the Refusal to File letter issued March 30, 2018 follows productive interactions with the Agency in which Alkermes clarified certain aspects of the NDA submission. No additional data or analyses were submitted by Alkermes to FDA.

"FDA's filing of the ALKS 5461 application is a positive step forward for patients suffering from major depressive disorder, a serious disease where inadequate response to existing antidepressants remains a well-known and significant treatment limitation, and where there have been no new pharmacological treatment approaches in 30 years," stated Craig Hopkinson, M.D., Chief Medical Officer and Senior Vice President of Medicines Development and Medical Affairs at Alkermes. "We will continue to engage with the FDA throughout the review process, as we work to bring this important medicine to patients."

The NDA filing for ALKS 5461 is based on results from a clinical efficacy and safety package with data from more than 30 clinical trials and more than 1,500 patients with MDD. Throughout the clinical development program, ALKS 5461 demonstrated a consistent profile of antidepressant activity, safety and tolerability in the adjunctive treatment of MDD.

Achaogen Announces FDA Advisory Committee Voted Unanimously in Favor of Plazomicin for Treatment of Adults with Complicated Urinary Tract Infections

Achaogen, Inc. (NASDAQ:AKAO), a late-stage biopharmaceutical company developing innovative antibacterials addressing multi-drug resistant (MDR) gram-negative infections, announced that the U.S. Food and Drug Administration's (FDA) Antimicrobial Drugs Advisory Committee voted on the two points for Advisory Committee consideration as follows:

1. Has the applicant provided substantial evidence of the safety and effectiveness of plazomicin for the treatment of complicated urinary tract infections?

Result: (15-0-0) There were 15 yes votes and zero no votes. No members of the panel abstained.

2. Has the applicant provided substantial evidence of the safety and effectiveness of plazomicin for the treatment of bloodstream infections in patients with limited or no treatment options?

Result: (4-11-0) There were four yes votes and 11 no votes. No members of the panel abstained.

There were 16 panel members at the meeting, one of whom departed prior to the vote and was therefore not present for the voting.

"We are encouraged by the Committee's unanimous vote in favor of plazomicin for complicated urinary tract infections (cUTI). The discussion underscored the real-world challenges that healthcare providers face every day given limited or inadequate treatment options for certain pathogens," said Blake Wise, Achaogen's Chief Executive Officer. "Regarding bloodstream infections, the Limited-Population Antibacterial Drug pathway, or LPAD, is a novel approach that enables the FDA to consider the benefits and risks for the sickest patients who have few or no available treatment options, and to approve antibiotics like plazomicin that we believe, have the potential to address these limited patient populations."

The FDA is not bound by the Committee's votes but takes its input into consideration when reviewing marketing applications. Plazomicin has a Prescription Drug User Fee Act (PDUFA) date of June 25, 2018. If the FDA approves plazomicin by this target action date, Achaogen expects to launch plazomicin in the U.S. soon thereafter.

http://investors.achaogen.com/releasedetail.cfm?ReleaseID=1066053

FDA Advisory Committee Votes in Favor of Waylivra (volanesorsen) for Treatment of Familial Chylomicronemia Syndrome

Akcea Therapeutics, Inc. (NASDAQ:AKCA), an affiliate of Ionis Pharmaceuticals, Inc., and Ionis Pharmaceuticals, Inc. (NASDAQ:IONS)   announced that the U.S. Food and Drug Administration’s (FDA) Division of Metabolism and Endocrinology Products Advisory Committee voted 12-8 to support approval of Waylivra (volanesorsen) for the treatment of people with familial chylomicronemia syndrome (FCS). The committee’s non-binding recommendation will be considered by the FDA in its review of Akcea’s New Drug Application for Waylivra. The PDUFA date for completion of the review of Waylivra is August 30, 2018.

3’—A*—G*—mC*—T*—T*—dmC—dT—dT—dG—dT—dmC—dmC—dA—dG—dmC—T*—T*—T*—A*—T*—5’




* = 2’-O-(2-methoxyethyl)

m = 5-methyl

d = 2’-deoxy

“We thank the committee members for their time and their comments today. The Committee’s majority vote in favor of approval is an important positive step to bring Waylivra to people with FCS who have no adequate treatment options,” said Paula Soteropoulos, chief executive officer of Akcea Therapeutics. “We look forward to working with the FDA to complete the final stages of regulatory review for Waylivra. We are committed to the FCS community and will continue to focus on bringing Waylivra, potentially the first and only treatment, to people living with this serious and potentially fatal disease.”

“Given the severity of FCS and the burden it places on patients, the need for a therapy is critical. The progress in development of a potential first-ever treatment is very encouraging. The planned efforts in monitoring and education are designed to achieve the highest levels of patient adherence, compliance and safety,” said Dr. Seth Baum, president, American Society for Preventive Cardiology. “The medical community is eager to have a medicine to treat our patients with FCS.”

The Advisory Committee reviewed data from two Phase 3 clinical trials, APPROACH and COMPASS, as well as the ongoing APPROACH Open Label study for Waylivra. Results from the phase 3 APPROACH trial, the largest study ever conducted in patients with FCS, show that patients with FCS treated with Waylivra achieved a statistically significant mean reduction in triglycerides of 77% from baseline and decreased risk of pancreatitis. The most common adverse events in the APPROACH study were injection site reactions and platelet declines. The Committee's input will be considered by the FDA in its review of the New Drug Application for Waylivra. The FDA is not bound by the Committee's guidance, but takes its advice into consideration when reviewing investigational medicines. Waylivra is also under regulatory review in the European Union and Canada.

“People with FCS have severely elevated triglycerides, which lead to multiple severe daily and chronic symptoms, such as abdominal pain and increased risk for pancreatitis, which can be fatal. Waylivra is the first drug to demonstrate substantial triglyceride lowering in clinical trials in people with FCS,” said Brett P. Monia, chief operating officer at Ionis. “Waylivra illustrates how our antisense technology can create targeted drugs for people living with severe diseases who currently have no available therapeutic options.”

Ref : http://ir.akceatx.com/news-releases/news-release-details/fda-advisory-committee-votes-favor-waylivra-treatment-familial

AcelRx Announces FDA Acceptance of NDA for DSUVIA

In continuation of my update on  sufentanil

AcelRx Pharmaceuticals, Inc. (Nasdaq: ACRX), (AcelRx or the Company), a specialty pharmaceutical company focused on innovative therapies for use in medically supervised settings, today announced the acceptance of its New Drug Application (NDA) resubmission for DSUVIA™ by the U.S. Food and Drug Administration (FDA). The FDA considers the DSUVIA NDA resubmission a complete class 2 response to their October 2017 action letter. Therefore, the FDA has assigned a PDUFA (Prescription Drug User Fee Act) goal date of November 3, 2018.

The acceptance of the DSUVIA NDA resubmission is yet another important milestone achieved by the Company this year," stated Vince Angotti, Chief Executive Officer of AcelRx. "We are one step closer to potentially delivering a new, non-invasive treatment option for the management of moderate-to-severe acute pain for adult patients in medically supervised settings. We believe DSUVIA, if approved, also has the opportunity to help U.S. hospitals manage through the intravenous opioid shortage1 they are currently experiencing in their facilities," continued Angotti.

About DSUVIA™ (sufentanil sublingual tablet), 30 mcg

DSUVIA™ (sufentanil sublingual tablet, 30 microgram), known as DZUVEO™ outside the United States, has a proposed indication for the management of moderate-to-severe acute pain in medically supervised settings, in adult patients and was designed to eliminate dosing errors associated with IV administration via its non-invasive single-dose applicator (SDA) administered by health care professionals. Sufentanil is an opioid analgesic currently marketed for intravenous (IV) and epidural anesthesia and analgesia. The sufentanil pharmacokinetic profile when delivered sublingually avoids the high peak plasma levels and short duration of action observed with IV administration. In Europe, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion, recommending approval of DZUVEO. A decision by the European Commission on whether to grant the marketing authorization is expected in the third quarter of 2018.

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AcelRx Announces FDA Acceptance of NDA for DSUVIA

FDA to Review Zynquista (sotagliflozin) as Potential Treatment for Type 1 Diabetes

The U.S. Food and Drug Administration (FDA) has accepted Sanofi's regulatory filing for Zynquista (sotagliflozin). The investigational oral treatment would be used in addition to insulin therapy to improve blood sugar control in adults with type 1 diabetes.

"If approved, Zynquista would be the first oral antidiabetic drug approved in the U.S. for use by adults with type 1 diabetes, in combination with insulin." says Jorge Insuasty, Senior-Vice President, Global Head of Development, Sanofi. "We look forward to working with the FDA through the review process with a view towards bringing this investigational medicine to adults with type 1 diabetes in the U.S."

Developed in partnership with Lexicon Pharmaceuticals, Inc., Zynquista is an investigational oral dual inhibitor of SGLT-1 and SGLT-2, proteins that influence how the intestines and kidneys absorb and eliminate sugar (glucose) resulting in improved glucose control and additional clinical benefits.

"After decades of little change and innovation, the treatment of type 1 diabetes has begun to shift significantly and, if approved, our dual SGLT-1 and SGLT-2 inhibitor, Zynquista, would be the first approved oral therapy used in combination with insulin to improve glycemic control and patient outcomes for adults in the United States who are living with type 1 diabetes," said Pablo Lapuerta, M.D., executive vice president and chief medical officer, Lexicon. "The acceptance of the NDA filing moves us closer to providing a meaningful option for people with type 1 diabetes and we look forward to continuing to work closely with the FDA during the review process."

The FDA New Drug Application for sotagliflozin is based on data from the inTandem clinical trial program which includes three Phase 3 clinical trials assessing the safety and efficacy of Zynquista in approximately 3,000 adults with inadequately controlled type 1 diabetes.1–3 The safety and efficacy data have not yet been evaluated by any regulatory authority.

The target FDA action date under the Prescription Drug User Fee Act (PDUFA) is anticipated to be March 22, 2019. Sanofi also submitted a regulatory application to the European Medicines Agency earlier this year.

TherapeuticsMD Announces FDA Approval of Imvexxy (estradiol vaginal inserts) for the Treatment of Dyspareunia Due to Menopause

In continuation of my update on estradiol

TherapeuticsMD, Inc., an innovative women's healthcare company,  announced that the United States Food and Drug Administration (FDA) has approved Imvexxy (estradiol vaginal inserts) for the treatment of moderate-to-severe dyspareunia (vaginal pain associated with sexual activity), a symptom of vulvar and vaginal atrophy (VVA), due to menopause. Imvexxy is the only product in its therapeutic class to offer a 4 mcg and 10 mcg dose, the 4 mcg representing the lowest approved dose of vaginal estradiol available.

"Imvexxy is a bio-identical vaginal estrogen product that offers a fraction of the estrogen contained in the average doses of many existing products currently on the market," said Brian Bernick, MD, Chief Clinical Officer of TherapeuticsMD. "Imvexxy is the only product specifically designed to be applicator-free. It dissolves completely without mess or additional clean-up, and can be used anytime of day. It allows women the freedom to immediately return to their normal daily activities. Studies showed that, in patients who used Imvexxy, systemic absorption of estradiol remained within postmenopausal range."

"We are excited to bring Imvexxy to market as TherapeuticsMD's first FDA-approved drug as we strive to be the premier Women's Health Company," said Robert Finizio, Chief Executive Officer of TherapeuticsMD. "Imvexxy reflects our long-standing corporate mission and commitment to health solutions that women want, based on the concepts of medical need, efficacy, safety, simplicity, and affordability. Imvexxy will be offered at a price in parity with other products that have been on the market for 10 to 30 years. By ensuring patients can access Imvexxy at an affordable price, TherapeuticsMD is doing the right thing for women."