FDA Approves Wixela Inhub (fluticasone propionate and salmeterol inhalation powder, USP), First Generic of Advair Diskus

In continuation of my updates on fluticasone propionate & salmeterol

              

Mylan N.V. (NASDAQ: MYL)  announced the U.S. Food and Drug Administration (FDA) approval of Wixela Inhub (fluticasone propionate and salmeterol inhalation powder, USP), the first generic of Advair Diskus.

Wixela Inhub will launch in the second half of February incorporating the latest safety information required by FDA earlier this month, which prompted an amendment to the label for certain inhaled corticosteroids, including Advair Diskus and any generic versions. Wixela Inhub will be available in the 100 mcg/50 mcg, 250 mcg/50 mcg and 500 mcg/50 mcg strengths for asthma patients and the 250 mcg/50 mcg strength for COPD patients.

Mylan CEO Heather Bresch commented, "Mylan remains steadfast in its efforts to expand patient access to medicines, and the FDA approval of Wixela Inhub reinforces our commitment to provide patients greater choice and lower-cost alternatives. This milestone represents the culmination of an extensive research and development program and Mylan's more than $700 million of investment. We're proud of our Wixela Inhub team, who worked tirelessly and in close collaboration with the FDA to bring this important medicine to market and add it to our growing global portfolio of more than 700 respiratory products. As one of the leading providers of prescription medicines in the U.S., we continue to execute on our mission and do our part to reduce costs for patients and identify pathways that help increase sustainability for the U.S. healthcare system overall."

Wixela Inhub is indicated for the twice daily treatment of asthma in patients age 4 and older not adequately controlled on long-term asthma control medications or whose disease warrants initiation of treatment with both inhaled corticosteroids and long-acting beta agonists; maintenance treatment of COPD; and the reduction of COPD exacerbations in patients with a history of exacerbations. It is not indicated for the relief of acute bronchospasm.

Mylan President Rajiv Malik added, "We're pleased to offer the first FDA-approved generic of Advair Diskus, one of the leading treatments for asthma and COPD management today. We've long been confident in the science around this product and are proud of the dedication of our scientific teams to bring Wixela Inhub to market. This complex product required a rigorous research and development program spanning over a decade and close collaboration with FDA to define the regulatory pathway. We also are proud to manufacture Wixela Inhub in our own state-of-the-art plant. This approval reinforces our ongoing commitment to increase access to more affordable treatment options for patients."

The research and development program for Wixela Inhub compared all strengths of treatment to Advair Diskus in order to meet the FDA requirements of therapeutic equivalence for a substitutable generic. In the 28-day, randomized, double-blind, placebo-controlled, parallel group study of 1,128 adult asthma patients conducted to evaluate the local (lung) bioequivalence of Wixela Inhub 100 mcg/50 mcg and ADVAIR DISKUS 100 mcg/50 mcg, the two treatments produced equivalent efficacy. Both treatments were safe and well-tolerated with lower numbers of withdrawals due to asthma compared to the placebo group. The study included both naive and current users of Advair Diskus.

"Patients enrolled in clinical trials found Wixela Inhub easy-to-use and highly effective at controlling their asthma in a clinical bioequivalence study. Asthma and respiratory specialists and primary care providers welcome this generic alternative to benefit many patients with asthma and COPD.  We have waited for years for generic inhalers to emerge in respiratory medicine," said Edward Kerwin, MD of Crisor LLC, a division of the Clinical Research Institute located in Medford, Ore. and a Clinical Investigator on the Wixela Inhub clinical program.

Advair Diskus had U.S. sales of $4.2 billion for the 12 months ending November 30, 2018, according to IQVIA.

https://en.wikipedia.org/wiki/Salmeterol

https://www.drugbank.ca/drugs/DB00588

FDA Approves Egaten (triclabendazole) for the Treatment of Fascioliasis, a Neglected Tropical Disease

Novartis announced that the US Food and Drug Administration (FDA) has approved Egaten (triclabendazole) for the treatment of fascioliasis in patients six years of age and older. This makes Egaten the only FDA-approved drug for people with this disease and is expected to facilitate broader access to this important drug not only in the US, but also in affected countries worldwide.

"Novartis has a long-standing commitment to addressing global health challenges and supporting disease elimination efforts, in diseases such as leprosy, malaria and fascioliasis," said Vas Narasimhan, CEO of Novartis. "Today's FDA approval of Egaten is another important milestone that we believe will help further expand access to this one-day treatment, taking us a step closer toward disease elimination."

Fascioliasis, commonly known as liver fluke infestation, is a neglected tropical disease that infects 2.4 million people worldwide[1], with an additional 180 million at risk of infection[2]. It is caused by two species of parasitic flatworms that can infect humans following ingestion of larvae in contaminated water or food.

Egaten is currently the only medicine for fascioliasis recommended by the WHO and is on the WHO Model List of Essential Medicines. It is supplied by WHO during epidemic outbreaks and for periodic use in endemic countries. FDA approval of Egaten is expected to facilitate drug licensing and import to these countries, helping ensure sufficient and prompt availability of the drug when needed. Fascioliasis is recognized by the FDA as a neglected tropical disease, triggering the award of a Priority Review Voucher based upon this approval.

Novartis has been donating Egaten to the WHO since 2005, helping to treat around 2 million fascioliasis patients in more than 30 countries. In 2018, we renewed our agreement with the WHO to extend the drug donation until 2022, expected to reach 300 000 patients per year.

"This FDA decision is welcome news for millions who suffer or are at risk of fascioliasis and removes a major hurdle in expanding treatment to countries where it is most needed," said Dr Mwelecela Malecela, Director of the Department of Control of Neglected Tropical Diseases at the WHO. "We are thankful to Novartis for their sustained decade-long commitment in tackling yet another disease of poverty."

https://en.wikipedia.org/wiki/Triclabendazole

PTSD Drug, Prazosin, May Do More Harm Than Good

In continuation of my update on prazosin

A drug used to treat post-traumatic stress disorder (PTSD) may actually be harmful, a new study suggests.

The high blood pressure drug prazosin is sometimes used to treat PTSD-related nightmares and insomnia that can increase suicide risk. But this small study suggests the drug may make nightmares and insomnia worse and not reduce suicidal thoughts in PTSD patients.

"I think we have to view this as not the final word on this, but it raises questions," said study author Dr. W. Vaughn McCall. He's chairman of psychiatry and health behavior at the Medical College of Georgia.

The study included 20 PTSD patients, including two military veterans and several civilian women who had been sexually assaulted. All had active suicidal thoughts, some had previously attempted suicide, and most were taking antidepressants and/or had them prescribed for the study.

For eight weeks, participants took prazosin at bedtime with an aim of preventing nightmares and suicidal thoughts. They were assessed weekly for severity of suicidal thoughts, nightmares, insomnia, depression and PTSD.

The drug "did not seem to do much for suicidal ideation and that was somewhat disappointing, but the thing what was mind-blowing was that it actually worsened nightmares," McCall said in a university news release. "Maybe it's not for everybody."

The unexpected increase in nightmares and insomnia might owe to the severity of a patient's PTSD or the once-a-day dose of prazosin, he said.

PTSD patients' nightmares often focus on the trauma that caused their PTSD, he said.

Two patients required emergency inpatient psychiatric care, but there were no suicide attempts or deaths during the study, which was published recently in the Journal of Clinical Psychopharmacology.

Prazosin may help some PSTD patients, but may not be a good choice when suicide is an active concern, according to McCall, who is now seeking input from PTSD experts across the United States

Two larger studies in active and retired military personnel yielded mixed results as well, he noted.

"We need to reconcile how is it that we had 10 years of data saying prazosin is good for nightmares in PTSD, a big study this February indicating it has essentially no [effect] and now a smaller study showing it can worsen some aspects," McCall said. "We need to know what it all means."

The antidepressants sertraline (Zoloft) and paroxetine (Paxil) are the only U.S. Food and Drug Administration-approved PTSD drug therapies, he said, adding that neither is widely effective.

Ref: https://journals.lww.com/psychopharmacology/Abstract/2018/12000/A_Pilot,_Randomized_Clinical_Trial_of_Bedtime.15.aspx

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Animal Study Suggests Ritalin Won't Harm the Heart

    

In continuation of my update on Ritalin 

Ritalin, a widely used stimulant drug to treat attention-deficit/hyperactivity disorder (ADHD), likely poses no risk of heart damage in children, new research in monkeys suggests.

The findings are "very reassuring," said the study's principal investigator, Dr. Steven Lipshultz.

Each year, more than 1.8 million children in the United States take drugs to treat ADHD. Concerns have been raised that Ritalin, Concerta and other forms of methylphenidate could harm children's hearts.

Some studies have reported an increase in sudden cardiac death among children taking methylphenidate or other stimulant drugs for ADHD.

But this new study found that five years of high doses of methylphenidate did not damage the hearts of 30 rhesus monkeys. That length of time is similar to how long children and adults would use the drugs.

"Even high-dose chronic [methylphenidate] stimulant therapy did not result in any evidence of abnormal structures or function in the hearts of the monkeys," said Lipshultz, chair of pediatrics at the University at Buffalo School of Medicine and Biomedical Sciences, in New York.

However, his team cautioned that the results of animal research are not automatically applicable to humans.

One ADHD specialist unconnected to the study agreed.

"The [animal] study cannot be automatically applicable to humans," said Dr. Victor Fornari, who directs child and adolescent psychiatry at Zucker Hillside Hospital in Glen Oaks, N.Y.

Still, the findings "provide compelling evidence of the cardiac safety of this important evidence-based treatment for ADHD," Fornari said.

About 10 percent of U.S. children have been diagnosed with ADHD and related disorders. Up to 70 percent of them take prescription stimulant drugs, so possible heart risks associated with the drugs are a major concern, study author Lipshultz said in a university news release.

The U.S. Food and Drug Administration has ordered some prescription stimulants to carry black box warnings stating that children with underlying heart disease should use these medications with caution.

In Canada, a stimulant drug was removed from the market after it was linked to a small number of sudden cardiac deaths. Sales of the drug later resumed.

"This controversy has persisted without answer," Lipshultz said. "Yet the number of prescriptions for these medications for children with ADHD continues to expand."

Another expert said the new findings should help ease concerns.

The study results "are overall re-assuring in terms of cardiac safety and long-term use of stimulants for ADHD in otherwise healthy individuals," said Dr. Andrew Adesman, chief of developmental and behavioral pediatrics at Cohen Children's Medical Center in New Hyde Park, N.Y.

However, he added that the study "does not address clinical concerns about the safety of stimulants in individuals with certain types of heart disease."

Therefore, "health care providers need to continue to screen children for cardiac problems prior to prescribing stimulant medications like Ritalin, Concerta or Adderall, since there are some individuals who may still be at increased risk for potentially serious heart problems if treated with stimulant medication," Adesman said.

Lipshultz noted that the findings are good news for another type of pediatric patient: young cancer survivors.

"I have cared for children and adolescents who have survived childhood cancer, who now are experiencing severe learning disabilities as a result of their cancer therapies. They become my patients because their hearts have been damaged, an unfortunate effect of the successful treatment of their childhood cancer," he said.

"Current recommendations state that children such as these, with underlying heart disease, should avoid chronic stimulant therapy because of the concern that it could further damage their hearts," he explained. "However, these prescription stimulants often allow these children to do much better with their learning progress."

The new findings suggest that, in many cases, these medications can be prescribed to these children as well, Lipshultz said.

Rituximab (Rituxan) May Delay MS Disability

In continuation of my update on rituximab

An immune system drug may help prevent or slow complications in a type of multiple sclerosis known as secondary progressive MS, a new study finds.

The medication is called rituximab (Rituxan). It's used to treat a number of conditions, including certain blood cell cancers and the autoimmune condition rheumatoid arthritis.

The new Swiss study found that MS patients taking the drug reported less disabling symptoms over a 10-year period than those who didn't. People taking rituximab also had a slower progression of MS symptoms.

It's important to note that the study was small, with 88 people, of whom only 44 received the medication, said Nicholas LaRocca, vice president of health care delivery and policy research for the National Multiple Sclerosis Society.

"This is a potentially valuable treatment, but there are still a lot of questions. Other studies are underway looking at the value of rituximab," LaRocca said.

With multiple sclerosis, the immune system turns against the central nervous system. Inflammation caused by the immune system damages a fatty substance called myelin that surrounds nerve cells, according to the National MS Society.

Symptoms of the disease vary from person to person, but may include fatigue, dizziness, problems walking, numbness or tingling, vision problems, pain, depression, bowel and bladder problems, muscle spasms and trouble with thinking and memory, according to the society.

MS usually begins as a relapsing-remitting disease. Sometimes it's active, and sometimes it's not. Most people with this form of MS will eventually transition to secondary progressive MS, which leads to more neurological problems and disability.

LaRocca said rituximab appears to work by affecting B-cells in the immune system. These cells have been implicated in the development of MS in other research, according to background information in the latest report.

In the study, researchers led by Dr. Yvonne Naegelin, from the University of Basel, Switzerland, compared 44 people with MS treated with rituximab to 44 people with MS who weren't given rituximab.

The volunteers who received rituximab were an average age of 50 and had been diagnosed with MS for about 18 years. The average age of the group that didn't receive rituximab was 51 and they had MS for an average of 19 years. The group that didn't receive rituximab was slightly less disabled, according to a disability scale.

Dr. Asaff Harel is a neurologist at Lenox Hill Hospital in New York City. He said, "This is an interesting, but limited, study that suggests that rituximab, a B-cell therapy, may be beneficial in the treatment of secondary progressive MS."

While those who got the drug tended to have lower progression of disabling symptoms, Harel said that "baseline differences in the two populations, such as age and the presence of relapses or new lesions, could cloud the results."

LaRocca said there was also a difference in the types of treatments the two groups had been exposed to prior to this study, which could have affected the results.

Rituximab isn't approved by the U.S. Food and Drug Administration for treating MS. Because of this, LaRocca said it wasn't clear if all insurance companies would cover its cost.

But, he said that it's reasonable for people to ask their physicians what they think of the drug and whether or not it might be an option for them.

Both experts said that more study is definitely needed to see if the drug is truly effective, along with answering other important questions, such as what's the optimal dose and how long can someone go between drug infusions?

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Rituximab (Rituxan) May Delay MS Disability for Some 

Psoriasis Meds Might Help Fight Heart Trouble, Too

 Could the inflammation that drives psoriasis and other immune-linked illnesses be a major player in heart disease?

In a new study, certain psoriasis drugs appeared to help to keep arteries clear, suggesting such a link.

"Classically a heart attack is caused by one of five risk factors: diabetes, hypertension, high cholesterol, family history or smoking," explained study lead researcher Dr. Nehal Mehta.

"Our study presents evidence that there is a sixth factor, inflammation," she said.

Mehta heads the Laboratory of Inflammation and Cardiometabolic Diseases at the U.S. National Heart, Lung, and Blood Institute (NHLBI) in Bethesda, Md.

Another cardiologist agreed the study could open doors to new research.

"The future of cardiovascular prevention may require a cholesterol reduction medication and an anti-inflammatory medication," said Dr. Guy Mintz, who directs heart health at Northwell Health's Sandra Atlas Bass Heart Hospital in Manhasset, N.Y.

"These are exciting times in the area of cardiovascular prevention," said Mintz, who wasn't involved with the study.

The new study involved 121 patients who had moderate to severe psoriasis and qualified for anti-inflammatory medicines called biologic therapies. These injected medicines are also used by people with immune-linked conditions such as lupus or rheumatoid arthritis, and include drugs such as Cimzia, Enbrel, Humira, Orencia and Remicade, among others.

All of these medicines work by helping to suppress pro-inflammatory immune system activity.

All participants enrolled in the new study were at low risk of heart disease at the beginning of the research.

Over a year of follow-up, the use of biologic therapy was associated with an 8 percent reduction in coronary artery plaque, the researchers said.

Specifically, use of biologic drugs appeared linked with a slowed buildup of fatty plaques in arteries. These are the plaques that can restrict blood flow and cause heart attacks and stroke.

The findings suggest that immunotherapies that treat inflammatory conditions might also help cut heart disease risk, Mehta and his colleagues reported.

The study authors pointed to prior research that tied psoriasis to the early development of high-risk "soft" arterial plaques. Biologic therapy might cut plaque formation, even in patients without other heart disease risk factors such as high cholesterol, blood sugar and blood pressure, they said.

"This appears to be an anti-inflammatory effect," Mehta explained in an NHLBI news release. "In the absence of improvement in other cardiovascular risk factors, and without adding new cholesterol medications, patients' soft plaque still improved."

However, a cause-and-effect relationship isn't clear from this type of study, so "the next steps should be randomized, controlled trials," Mehta said.

Dr. Michele Green is a dermatologist who treats psoriasis patients at Lenox Hill Hospital in New York City. She wasn't involved in the new study, but said that "treatments with biologics indeed shows great promise in treating cardiovascular disease."

As for Mintz, he called the new research "exciting and important, because it highlights the importance of inflammation associated with psoriasis causing blockages in the arteries of the heart to progress.

"The best statin in the world can only lower cardiovascular events by approximately 40 percent," Mintz pointed out. "So the question arises, what causes the other 60 percent of cardiovascular events?"

The new research "supports the hypothesis that inflammation contributes to cardiovascular disease," he said. "Physicians need to become aware that inflammation should be considered in patient cardiovascular risk assessment."

New class of sleeping pill preserves ability to wake in response to danger signals

https://chem.nlm.nih.gov/chemidplus/rn/1088991-95-0

In a trial of one of the main class of prescription sleeping pills, half the participants slept through a fire alarm as loud as someone vacuuming next to their bed. But a newer alternative preserves the ability to wake in response to danger signals, according to a new research.

Published this week in Frontiers in Behavioral Neuroscience, the study showed that mice given the experimental hypnotic drug DORA-22 wake as quickly when threatened as drug-free sleepers - and then fall back asleep as quickly as ones given standard sleeping pills, once the threat is gone.

Common sleeping pills muffle your sleeping brain's 'intruder alert'

Even during sleep the brain continuously processes sensory information, waking us if it detects a threat. But the most widely prescribed class of sleeping pills, known as benzodiazepines, makes us less likely to rouse in response to sensory input.

"Benzodiazepines stimulate the widespread brain receptor GABA-A, which makes us sleepy but also suppresses off-target brain areas - including the 'gatekeeper' that decides which sensory inputs to process," explains study senior author Professor Tomoyuki Kuwaki of Kagoshima University, Japan.

Over the last decade, researchers have been developing a new class of hypnotic drugs called dual orexin receptor antagonists (DORAs). DORAs more selectively target the brain's sleep/wake pathways, which gives them safety advantages over benzodiazepines. These include a reduced 'hangover effect', with DORAs less likely to affect driving ability the day after use.

Kuwaki and colleagues hypothesized that the selectivity of DORAs could make them a safer alternative during sleep as well - by allowing the brain's sensory gatekeeper to stay vigilant to threats.

DORA-22 allows mice to wake to a threat, but still helps them sleep

The group tested their theory in mice.

The mice were dosed and tested after dark, when they are normally most active. One group was administered DORA-22, another a benzodiazepine called triazolam - and a third group was given placebo as a control.

"DORA-22 and triazolam had similar sleep promoting effects, extending the duration of deep sleep by 30-40% compared to placebo," reports Kuwaki.

One to four hours after dosing, the deep-sleeping mice were presented with a threatening stimulus: the smell of a fox, a high-pitched noise like a dog whistle, or trembling of their cage. The trembling frequency was designed to match that of an earthquake - a serious threat in Kuwaki's native Japan and many other parts of the word.

"As expected, arousal in response to these threatening stimuli was delayed significantly in the triazolam treatment, but not in the DORA-22 treatment, compared to placebo.

Even more promising, the sleep-promoting effect of DORA-22 remained after the rude awakening.

"Even though the DORA-22-treated mice were quickly woken by a threat, they subsequently fell back asleep as quickly as with triazolam, and significantly faster than with placebo."

To help demonstrate that the delay in waking to a threat during triazolam treatment was due specifically to inhibition of sensory gating in the brain, the researchers also tested the sleeping mice with a non-sensory stimulus.

"The three groups woke equally quickly when we suddenly reduced the amount of oxygen in their cage. This suggests that the delay in rousing to threatening stimuli caused by triazolam was not caused by a general inhibition of waking systems in the brain."

Human studies are needed to confirm DORA safety and efficacy

"Although it remains to be seen whether DORAs have the same properties when used in humans, our study provides important and promising insight into the safety of these hypnotics."

Since 2014, another DORA called surovexant has gained regulatory approval in Japan, the USA and Australia. So far, the high cost and limited clinical testing of surovexant have limited its use, amid concerns that doses high enough to significantly improve sleep lead to drowsiness the following day. New DORAs currently in development could overcome this hangover effect if they are cleared more quickly from the body than suvorexant, so that their effects are less likely to last beyond bedtime. Keep your eyes peeled.

Good News, Bad News on Levodopa for Parkinson's Disease

In continuation of my update on L-Dopa

The most potent drug available for Parkinson's disease, levodopa, treats symptoms of the disease but does nothing to either ease or increase its still-mysterious underlying causes, a new clinical trial has concluded.

Doctors often delay prescribing levodopa, or L-dopa, to Parkinson's patients for fear that the drug might have toxic effects that produce jerky involuntary body movements over time.

But patients started on L-dopa nearly a year earlier than a second group did not develop significantly different rates of involuntary movement, results from the new trial show.

"The current study bolsters our confidence that levodopa is safe even in early Parkinson's disease and that patients should not fear it," said Dr. Michael Okun. He's the national medical director of the Parkinson's Foundation and chairman of neurology at the University of Florida in Gainesville.

There's disappointment here as well. While levodopa isn't toxic, it also doesn't appear to provide any protection against progression of Parkinson's in the brain, said Dr. Susan Bressman, co-director of the Mount Sinai Parkinson and Movement Disorders Center in New York City.

"The bottom line is they couldn't show neuroprotection," Bressman said. "Using this very normal dose we normally use, they couldn't show it slows the progression of the disease."

Parkinson's disease is a progressive nervous system disorder. One of its hallmarks is the loss of neurons that produce a brain chemical called dopamine. Low dopamine levels affect a person's control over their movements, causing tremors, rigid muscles and slowness.

Developed more than 50 years ago, L-dopa eases these muscular and movement symptoms. The brain synthesizes levodopa into dopamine and then puts the neurotransmitter to good use.

"Levodopa remains the most important and effective treatment for Parkinson's disease and its introduction has undoubtedly improved morbidity, mortality and quality of life," said Okun, who wasn't part of the trial.

But side effects in some patients cause concern that the drug might have a toxic effect on the brain, researchers noted.

A clinical trial 14 years ago that aimed to clear up the matter only muddied the waters, Bressman said.

The earlier trial found that people taking L-dopa showed improvement even after they stopped taking it, raising hopes that it might be somehow be stemming the progression of Parkinson's.

But brain scans of those patients showed some evidence that levodopa was causing potentially harmful changes to dopamine receptors in the brain, Bressman said.

"We couldn't really prove one way or the other if it's good or bad for the brain," Bressman said. "But the bottom line -- people need it. We don't have a better drug. It's the most potent drug for the symptoms, so you've got to use it, but you don't use a high dose."

The new clinical trial, led by Dr. Rob de Bie from the University of Amsterdam, hoped to clarify results of the older study.

A group of 445 early Parkinson's patients in the Netherlands were randomly assigned to either start levodopa therapy right away, or wait 40 weeks and then start taking the drug.

"The theory is if you get those extra 40 weeks of exposure to levodopa and it's neuroprotective, the earlier group will be in a better place and the late group will never catch up," Bressman said. "They'll always be a little worse because the first group got more of this neuroprotective effect."

But both groups wound up in the same place by week 80 of the trial, with essentially the same rate of disease progression, the Dutch researchers found. The drug didn't provide people in the earlier group any extra protection.

At the same time, neither group suffered greater rates of jerky movements or levodopa-related fluctuations in motor response, discounting concerns over toxic effects.

"Basically, it confirms what we currently do," said Bressman, co-author of an editorial accompanying the study. Both were published in the Jan. 24 issue of New England Journal of Medicine.

"Most people don't start levodopa at first diagnosis, when they have hardly any symptoms, because they don't need it. We don't think the drug is protecting the brain, so we don't start it right away, because it's not going to change what they're going to look like 10 years down the pike," she noted.

"But as soon as they do start to need it, we start it. We use it. And we're judicious in how we use it," Bressman continued.

Hopes for a drug that will directly treat or perhaps even cure Parkinson's now rest on research being done into suspected causes of the disease, she said.

Experts now think Parkinson's is a related group of diseases, each subtype potentially triggered by a different cause, Bressman said.

Drugs are being developed to target genes that have been implicated in Parkinson's for some patients. Future drugs might target inflammation in the brain or other potential causes.

"I think ultimately between the genetics and other biomarkers we find in the spinal fluid or in the blood, we're going to be able to group patients better and figure out the disease mechanisms," Bressman said.

https://en.wikipedia.org/wiki/L-DOPA

Good News, Bad News on Levodopa for Parkinson's Disease 

Prostate Drug Finasteride Can Safely Lower Cancer Risk, Study Says

In continuation of my update on Finasteride

Finasteride, best known as the enlarged-prostate medicine Proscar, is a safe, effective way to reduce the risk of prostate cancer, according to long-term findings from the Prostate Cancer Prevention Trial (PCPT).

The trial was funded by the U.S. National Cancer Institute and enrolled nearly 19,000 men between 1993 and 1997.

Initially it found that finasteride -- a hormone-blocking drug -- cut the risk of prostate cancer by 25 percent. Those results were published in 2003.

The newly released long-term data show that the reduction of prostate cancer risk has continued and that fewer than 100 men in the trial died from prostate cancer in more than two decades of follow-up, according to a research team led by Dr. Ian Thompson.

The updated results also showed no statistically significant increased risk of death from prostate cancer among men taking finasteride. This removes concerns over early findings of a possible risk of more aggressive cancers among patients who take the drug.

"Finasteride is safe, inexpensive and effective as a preventive strategy for prostate cancer," said Thompson, who is principal investigator of the PCPT for the SWOG Cancer Research Network.

The SWOG Cancer Research Network is an international cancer clinical trials group.

"Doctors should share these results with men who get regular prostate-specific antigen [PSA] tests that screen for the presence of prostate cancer," Thompson said in a SWOG news release. "The drug will have its greatest effect in this group of men."

Thompson is also emeritus professor at the University of Texas Health Science Center. He and his team published their findings Jan. 23 in the New England Journal of Medicine.

A cheap, reliable prostate cancer prevention drug will have a big impact on public health, Thompson and his colleagues said.

They noted that prostate cancer rates are on the rise and that nearly 165,000 American men were diagnosed with the cancer in 2018, according to the American Cancer Society.

Many cases of prostate cancer are slow-growing and not life-threatening, but are still often treated with surgery and radiation, sometimes resulting in complications such as impotence and incontinence.

"There are significant negative consequences to patients' health and quality of life that can result from prostate cancer treatment, as well as to their finances and their peace of mind," Thompson said.

"If we can save people from surgeries and scores of examinations and tests, and spare them from living for years with fear, we should. The best-case scenario for patients is prevention, and this trial has found an inexpensive medication that gets us there," he concluded.

One prostate specialist unconnected to the research said the new findings come after "many years of debate" on finasteride's role in cancer prevention.

Based on early findings from the PCPT, the U.S. Food and Drug Administration "issued a warning that chronic use of the medication may increase the risk of high-grade or aggressive prostate cancer in a small percentage of men," said Dr. Manish Vira. He helps direct urologic research at Northwell Health's Arthur Smith Institute for Urology in Lake Success, N.Y.

Unfortunately, that warning "effectively nullified the benefits of the medication in the eyes of many patients and their physicians," Vira said.

These later, fuller results should turn that around, he noted.

"Physicians and patients need to be aware of these results, and at least consider again using these medications in the prevention of prostate cancer," Vira said."This may be especially true among men at high risk, such as African-American men and men with a strong family history of prostate cancer," he said.

https://en.wikipedia.org/wiki/Finasteride

https://www.webmd.com/drugs/2/drug-1548-167/finasteride-oral/finasteride-oral/details

Prostate Drug Finasteride Can Safely Lower Cancer Risk, Study Says 

US FDA Accepts Regulatory Submissions for Review of Tafamidis to Treat Transthyretin Amyloid Cardiomyopathy

In continuation of my update on Tafamidis

Pfizer Inc. (NYSE: PFE) announced today that the US Food and Drug Administration (FDA) accepted for filing the company’s New Drug Applications (NDAs) for tafamidis for the treatment of transthyretin amyloid cardiomyopathy (ATTR-CM). Pfizer has submitted two NDAs based on two forms of tafamidis: meglumine salt and free acid. Tafamidis is the only product to complete a Phase 3 trial evaluating its efficacy, safety, and tolerability in patients with ATTR-CM, a rare, fatal, and underdiagnosed condition.1,2

The tafamidis meglumine form (20 mg capsule) has been granted Priority Review. The FDA grants Priority Review to medicines that may offer significant advances in treatment or may provide a treatment where no adequate therapy exists. The target Prescription Drug User Fee Act (PDUFA) action date for a decision by the FDA is in July 2019.

The tafamidis free acid form (61 mg capsule) will be under Standard Review. This form is bioequivalent to the 80 mg tafamidis meglumine dose, which was administered as four 20 mg capsules in the pivotal trial; it was developed for patient convenience to enable a single capsule for daily administration. The target PDUFA action date for a decision by the FDA is in November 2019.

“The diagnosis of ATTR-CM is often delayed, primarily because disease awareness is low and patients often present with symptoms similar to more common causes of heart failure. In fact, we believe less than one percent of patients living with this disease are currently diagnosed,” said Brenda Cooperstone MD, Senior Vice President and Chief Development Officer, Rare Disease, Pfizer Global Product Development. “The FDA’s filing acceptance is an encouraging step toward our goal of further raising awareness and providing a treatment option for ATTR-CM patients who are in desperate need of an approved pharmacologic therapy. We look forward to working with the FDA to bring the first treatment for this deadly disease to patients.”

The submission is based on findings from the pivotal Phase 3 Transthyretin Amyloid Cardiomyopathy (ATTR-ACT) study, which evaluated the efficacy, safety, and tolerability of tafamidis meglumine compared to placebo for the treatment of patients with ATTR-CM. In the primary analysis of the study, tafamidis met the primary endpoint, demonstrating a significant reduction in the hierarchical combination of all-cause mortality and frequency of cardiovascular-related hospitalizations compared to placebo over a 30-month period in patients with wild-type or hereditary ATTR-CM (P=0.0006). Tafamidis was well tolerated, with an observed safety profile comparable to placebo.3 The primary results were presented in a Hot Line session at the ESC Congress 2018 in Munich, Germany, and simultaneously published online in the New England Journal of Medicine (NEJM) in August 2018. Results from additional sub-group analyses were presented during the Late Breaking Clinical Trials session at the Heart Failure Society of America 22nd Annual Scientific Meeting in Nashville, TN, in September 2018. For more information on the ATTR-ACT trial, go to www.clinicaltrials.gov.

https://en.wikipedia.org/wiki/Tafamidis

US FDA Accepts Regulatory Submissions for Review of Tafamidis to Treat Transthyretin Amyloid Cardiomyopathy