FDA Approval to Expand the Age Range for Ravicti (glycerol phenylbutyrate) Oral Liquid to Include Newborns

  In  continuation of my update on   glycerol phenyl butyrate   

        Horizon Pharma plc (NASDAQ: HZNP) announced the U.S. Food and Drug Administration (FDA) has approved a supplemental new drug application (sNDA) to expand the age range for Ravicti (glycerol phenylbutyrate) Oral Liquid to include infants younger than two months of age living with a urea cycle disorder (UCD).

Ravicti is now FDA-approved for use as a nitrogen-binding agent for chronic management of UCDs in adults and children of all ages who cannot be managed by dietary protein restriction and/or amino acid supplementation alone. Ravicti must be used with dietary protein restriction and, in some cases, dietary supplements. Ravicti is not indicated for treatment of acute hyperammonemia in patients with UCDs, and its safety and efficacy for the treatment of n-acetylglutamate synthase (NAGS) deficiency has not been established.

“The FDA approval of Ravicti for children younger than two months provides a new alternative for the management of patients with a UCD that is easy to dose and administer to infants given the liquid formulation,” said Nicola Longo, M.D., Ph.D., clinical geneticist at Primary Children’s Hospital and the University of Utah Hospital, and a lead investigator of a clinical study evaluating Ravicti for newborns. “UCDs are severe and can be life-threatening. We hope that the combination of early diagnosis – through newborn screening or by measurement of ammonia levels – and the availability of novel treatments, such as this one, can help to improve the outcome of affected patients.”

A study was conducted to assess safety, efficacy and pharmacokinetics in pediatric patients with UCDs two months of age and younger (n=16). In the study, 10 patients transitioned to Ravicti from sodium phenylbutyrate, three transitioned from intravenous sodium benzoate and sodium phenylacetate, and three were treatment naïve. Patients were treated with Ravicti for an average of 10.7 months. Results demonstrated safety and efficacy in children younger than two months, with Ravicti-treated patients maintaining stable ammonia levels relative to their pre-study enrollment. In addition, mean ammonia levels were lower during treatment with Ravicti compared to baseline values.

“As we increase our efforts to develop new investigational medicines for people living with rare and rheumatic diseases, Horizon continues to seek ways to better serve patients with our current medicines,” said Elizabeth Thompson, Ph.D., vice president, clinical development, rare diseases, Horizon Pharma. “The FDA approval of Ravicti for children under the age of two months is a milestone in our efforts to help people living with UCDs, and we are proud to be bringing a new treatment option to the vulnerable newborn patient population.”

A UCD is a rare genetic disorder that affects approximately 1 in 35,000 live births in the United States. It is caused by an enzyme deficiency in the urea cycle, a process that is responsible for converting excess ammonia from the bloodstream and ultimately removing it from the body. Because of this, people with a UCD experience hyperammonemia, or elevated ammonia levels in their blood, that can then reach the brain and cause irreversible brain damage, coma or death. UCD symptoms may first occur at any age depending on the severity of the disorder, with more severe defects presenting earlier in life. 

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Horizon Pharma plc Announces FDA Approval to Expand the Age Range for Ravicti (glycerol phenylbutyrate) Oral Liquid to Include Newborns

FDA Approves ProAir Digihaler (albuterol sulfate) as the First and Only Digital Inhaler with Built-In Sensors

In continuation of my update on albuterol

Teva Pharmaceutical Industries Ltd., announced  that the U.S. Food and Drug Administration (FDA) has approved ProAir ® Digihaler™ (albuterol sulfate 117 mcg) inhalation powder, the first and only digital inhaler with built-in sensors which connects to a companion mobile application and provides inhaler use information to people with asthma and COPD. ProAir ® Digihaler™ is indicated for the treatment or prevention of bronchospasm in patients aged four years and older with reversible obstructive airway disease, and for prevention of exercise-induced bronchospasm (EIB) in patients aged four years and older.

“This approval marks a significant milestone not only for Teva, but for the respiratory community as it allows patients and their caregivers to better understand inhaler usage through digital technology,” said Sven Dethlefs, Executive Vice President, Global Marketing & Portfolio. “Teva recognizes the importance of integrating technology into patient care, and we are very proud to lead the way with the approval of ProAir ® Digihaler™. The digital technology built into ProAir ® Digihaler™ provides patients with data on their inhaler use, which may help them to have a more informed dialogue with their healthcare provider regarding their asthma or COPD management.”

ProAir ® Digihaler™ contains built-in sensors that detect when the inhaler is used and measure inspiratory flow. This inhaler-use data is then sent to the companion mobile app using Bluetooth ® Wireless Technology so patients can review their data over time, and if desired, share it with their healthcare professionals.

“There are 25 million Americans living with asthma1, many of whom use inhalers as part of their treatment regimen. Despite advancements in care over the years, we know that many are using their rescue medications incorrectly2 or too often3,” said Tonya Winders, President & CEO of the Allergy & Asthma Network. “The FDA approval of ProAir ® Digihaler ™ is significant because it may help patients track their inhaler usage and provide data that can be used to work more closely with their HCPs on their asthma management. This approval is a major step forward and is indicative of how medications are evolving through technological innovations.”

The approval of ProAir ® Digihaler™ is based on the review of a supplemental new drug application (sNDA) submitted by Teva to the FDA. ProAir ® Digihaler™ combines a breath-activated, multi-dose dry powder inhaler with albuterol, the most widely used asthma rescue medication, with a built-in electronic module and a companion mobile app.

“One of the challenges physicians are faced with in caring for their asthma and COPD patients is knowing if their patients are using their inhaled medication as they should. That’s what makes a product like this so important to doctor-patient discussions,” said Tushar Shah, M.D., Global Head of Specialty Clinical Development & Medical Affairs at Teva Pharmaceuticals. “Offering a tool that enables doctors to see data on their patients’ inhaler usage will allow them to have more productive conversations about identifying issues and how to manage their illness.”

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FDA Approves ProAir Digihaler (albuterol sulfate) as the First and Only Digital Inhaler with Built-In Sensors

FDA Approves Inbrija (levodopa inhalation powder) for Intermittent Treatment of OFF Episodes in People with Parkinson’s Disease

In continuation of my update on Levodopa

Acorda Therapeutics, Inc. today announced that the U.S. Food and Drug Administration approved Inbrija™ for intermittent treatment of OFF episodes in people with Parkinson’s disease treated with carbidopa/levodopa. OFF episodes, also known as OFF periods, are defined as the return of Parkinson’s symptoms that result from low levels of dopamine between doses of oral carbidopa/levodopa, the standard oral baseline Parkinson’s treatment.

“Today’s approval of Inbrija marks a major milestone for both Acorda and the Parkinson’s community, for whom we are gratified to have developed this much needed therapy,” said Ron Cohen, M.D., Acorda President and CEO. “This milestone resulted from over two decades of research and development, beginning in the laboratory of Dr. Robert Langer at Massachusetts Institute of Technology, through years of enormous perseverance and ingenuity by the entire Acorda team.”

“Despite being on treatment, patients may experience OFF periods as Parkinson’s progresses, which can be disruptive,” said Todd Sherer, Ph.D., CEO, The Michael J. Fox Foundation. “The Foundation provided funding for the early clinical development of Inbrija because patients told us that OFF periods were one of their most serious issues. We knew we had to help address this unmet need, and this approval is a significant step forward for the community as it provides a new option to manage these gaps in symptom control.”

“In the clinical study program, Inbrija established its safety profile and demonstrated clinically meaningful improvements in motor function, as measured by the UPDRS Part III,” said Robert A. Hauser, M.D., MBA, Professor of Neurology and Director of the Parkinson's Disease and Movement Disorders Center at the University of South Florida. “Inbrija helps address a significant unmet need for people with Parkinson’s, and we look forward to adding this new treatment option to our armamentarium.”

FDA approval of Inbrija was based on a clinical program that included approximately 900 people with Parkinson’s on a carbidopa/levodopa regimen experiencing OFF periods. Inbrija is not to be used by patients who take or have taken a nonselective monoamine oxidase inhibitor such as phenelzine or tranylcypromine within the last two weeks.

“I’m delighted that Inbrija has been approved and may be added to patients’ existing Parkinson’s medications for on-demand use, based on individual patient need,” said Burkhard Blank, M.D., Chief Medical Officer of Acorda. “We thank the FDA for a constructive dialogue throughout the development program and their partnership during the review cycle. We especially thank all those who volunteered for the Inbrija clinical trials, without whose commitment new medications could not be developed. And we are grateful for the people living with Parkinson’s, their care partners, researchers, clinicians and advocacy groups, who have all collaborated with us to help achieve this milestone.”

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FDA Approves Inbrija (levodopa inhalation powder) for Intermittent Treatment of OFF Episodes in People with Parkinson’s Disease

Naloxone Nasal Spray Works Best to Stop Opioid OD...

In continuation of my update on naloxone

A one-step nasal spray is the easiest form of naloxone to give someone suffering an opioid overdose, researchers say.

Increased public availability of naloxone, also known by the brand name Narcan, is considered a key way to reduce opioid overdose deaths. But there's more than one way to administer it, and it wasn't clear which method would be most successful when given by a bystander.

In this study, 138 adults watched a two-minute video demonstrating how to administer naloxone using one of the three methods -- two nasal sprays and one intramuscular shot. Each participant then selected one method to administer naloxone to a mannequin.

The study participants had a higher rate of success with the single-step nasal spray than with an intramuscular naloxone injection. They administered the one-step nasal spray faster than either a multi-step atomized spray or shot.

"With training, nasal sprays in general had a higher degree of success than the shot," said study author William Eggleston. He's a clinical assistant professor in the School of Pharmacy and Pharmaceutical Sciences at Binghamton University in New York.

"Even if it seemed to us it was a no-brainer that we should be using nasal sprays, we had no data before, so now we have some to support that," he said in a university news release.

https://en.wikipedia.org/wiki/Naloxone#/media/File:Naloxone.svg

Cassipa Approved for Opioid Dependence

In continuation of my update on buprenorphine and naloxone

                                           

Cassipa (buprenorphine and naloxone), a film designed to be placed under the tongue, has been approved to treat opioid dependence, the agency said in a news release.

Both buprenorphine and naloxone have been approved previously for this purpose.

"Opioid replacement therapy can be an important part of effective treatment," said FDA Commissioner Dr. Scott Gottlieb. "Opioid use disorder should be viewed similarly to any other chronic condition that is treated with medication."

The newly approved drug duo should be part of a complete treatment plan that includes counseling and psychosocial support to treat people with opioid use disorder. Cassipa may only be dispensed by approved prescribers, the agency said.

Side effects of the drugs include oral numbness, burning mouth, inflammation of the mouth's mucous membrane, headache, nausea, vomiting, excessive sweating and constipation.

Cassipa is produced by Teva Pharmaceuticals USA, based in New Jersey. Its parent company is located in Israel.

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

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

Coffee May Have Another Perk for Kidney Patients

In continuation of my update on coffee

The benefit remained "even after considering other important factors such as age, gender, race, smoking, other diseases and diet," according to one of the study's lead authors, Miguel Bigotte Vieira, of North Lisbon Hospital Center in Portugal.

In the study, Vieira's team tracked data on 4,863 U.S. chronic kidney disease patients monitored from 1999 to 2010.

Although the study couldn't prove cause-and-effect, it found that greater caffeine intake was tied to greater life expectancy for people with chronic kidney disease.

Compared to those who consumed very little caffeine per day, people with caffeine intake in the high range had about a 25 percent lower risk of death over an average follow-up of five years.

People who consumed the most caffeine tended to be white and male, with more education and higher incomes. They were also more likely to be current or former smokers and heavier drinkers than those who drank only small amounts of caffeine.

The findings were published Sept. 12 in Nephrology Dialysis Transplantation.

According to the researchers, chronic kidney disease affects 14 percent of American adults, leading to higher health care costs and a greater risk of death.

So, simply drinking more coffee or other caffeine-laden beverages "would represent a simple, clinically beneficial and inexpensive option, though this benefit should ideally be confirmed in a randomized clinical trial," Vieira said in a journal news release.

One U.S. endocrinologist who wasn't connected to the study said there could be physiologic reasons behind the benefit.

"Coffee has had a bad reputation, but this study showed that people who drink coffee did better," said Dr. Robert Courgi, of Southside Hospital in Bay Shore, N.Y."Perhaps it is because coffee may help the blood vessels function better through nitric oxide," he said. Nitric oxide is a key player in healthy blood vessel function.

Ref: https://medlineplus.gov/caffeine.html

FDA Finds Another Carcinogen in Certain Valsartan Heart Meds

In continuation of my updates on Valsartan

There's more bad news for Americans who took certain brands of the common blood pressure medication valsartan.

The U.S. Food and Drug Administration on Thursday warned that it has found a second impurity in three lots of Torrent Pharmaceuticals' valsartan drug products, which are used to treat both high blood pressure and heart failure.

The FDA first recalled valsartan medicines back in July, after the Chinese company that makes the drugs, Zhejiang Huahai Pharmaceuticals, found a contaminant called N-nitrosodimethylamine (NDMA) in several batches of its active ingredient, valsartan API.

NDMA is a suspected carcinogen. However, there was some reassurance earlier this week for people who had used the recalled Chinese-made product. A study involving more than 5,000 patients followed for nearly five years found those who took the recalled valsartan were not more likely to develop cancer in the short term. Long-term cancer risk remains unclear, however.

Now, in a news release issued Thursday, the FDA said Torrent's valsartan 160 milligram (mg) (lot BV47D001) and 320mg (lots BV48D001 and BV48D002) tablets are also tainted with N-Nitrosodiethylamine (NDEA). NDEA is also classified as a possible cancer-causing agent by the U.S. Environmental Protection Agency.

Contamination by both NDMA and NDEA could result from a specific sequence of manufacturing steps and chemical reactions, the FDA explained. After NDMA was detected, the agency immediately began retesting all valsartan products, including the already recalled drugs and others sold in the United States, the agency explained.

The FDA's testing shows that not all products made using Zhejiang Huahai Pharmaceuticals' valsartan API contain the potentially dangerous impurities.

"As we continue to investigate the root cause of the impurities found in products that contain valsartan, our scientists are testing these products to better understand these impurities and to ensure they're not present in other products," FDA Commissioner Dr. Scott Gottlieb said in the news release.

He said the FDA is also taking steps to prevent similar contaminations in the future, and providing the public with up-to-date information.

"We'll also continue to work with global regulatory agencies to learn as much as we can about how these impurities came about and how they may affect patients' health around the globe," Gottlieb added.

The agency has created a running list of affected products, and urges all patients taking a valsartan drug to check the list periodically to see if their medication is affected.

If you find that you are taking a drug that's included in the recall, talk to your doctor immediately, the FDA said. People using a recalled valsartan drug should not discontinue treatment until their doctor prescribes them an alternative medication, the agency said.

FDA Approves Xelpros (latanoprost ophthalmic emulsion) to Treat Open-angle Glaucoma or Ocular Hypertension

In continuation of my update on latanoprost

Sun Pharmaceutical Industries Ltd. and Sun Pharma Advanced Research Company Ltd. (SPARC) announced U.S. Food and Drug Administration (USFDA) approval for the New Drug Application (NDA) of Xelpros (latanoprost ophthalmic emulsion) 0.005% for the reduction of elevated intraocular pressure (IOP, or pressure inside the eye) in patients with open-angle glaucoma or ocular hypertension. This approval is from Sun Pharma’s Halol (Gujarat, India) facility.

Sun Pharma in-licensed Xelpros from SPARC in June 2015 and this approval will trigger a milestone payment to SPARC. SPARC is also eligible for milestone payments and royalties on commercialization of Xelpros in the US.

Xelpros is the first and only form of latanoprost that is not formulated with benzalkonium chloride (BAK), a preservative commonly used in topical ocular preparations. Xelpros is developed using SPARC’s proprietary Swollen Micelle Microemulsion (SMM) technology.

“As the only BAK-free version of latanoprost, Xelpros will be an important and alternative treatment option for individuals with open-angle glaucoma or ocular hypertension,” said Abhay Gandhi, CEO, North America, Sun Pharma. “This approval, coming less than one month following the approval of CEQUA™ (cyclosporine ophthalmic solution) 0.09%, reaffirms the strength of Sun Pharma’s fast-growing Ophthalmics division and its commitment to serving the needs of patients with ocular disorders.”

Anil Raghavan, CEO, SPARC said, “Approval of Xelpros by USFDA is a significant milestone for SPARC. It is also a validation of our SMM technology which helps to solubilize drugs that have limited or no solubility thus eliminating the need for benzalkonium chloride (BAK).”

In randomized, controlled clinical trials of patients with open-angle glaucoma or ocular hypertension with a mean baseline Intraocular pressure (IOP) of 23-26 mmHg, Xelpros lowered IOP by a mean of up to 6-8 mmHg.

Xelpros will be commercialized in the U.S. by Sun Ophthalmics, the branded ophthalmic division of Sun Pharmaceutical Industries Ltd.’s wholly owned subsidiary.

Breast Cancer Drug Promising in Phase 3 Trial

 For women with advanced breast cancer who carry the BRCA1 and BRCA2 gene mutations, an experimental drug could improve survival, a new study suggests.

The BRCA mutations are linked with a greater risk for aggressive breast and ovarian cancer. The drug, talazoparib, works by blocking an enzyme called poly ADP ribose polymerase (PARP), thus preventing cancer cells from killing healthy ones.

In a phase 3 trial of 431 women, funded by the drug's maker, those who received talazoparib lived longer without their cancer progressing than women treated with standard chemotherapy by an average of three months, researchers found.

"For women with metastatic breast cancer and a BRCA mutation, PARP inhibitors may be considered for their treatment," said lead researcher Dr. Jennifer Litton, an associate professor of breast medical oncology at the University of Texas M.D. Anderson Cancer Center in Houston.

When it's functioning properly, BRCA actually helps repair damaged DNA and prevents tumors, but when BRCA1 and BRCA2 go awry, they encourage breast cancers.

PARP inhibitors such as talazoparib appear to interfere with the function of mutated BRCA in breast cells, causing them to die rather replicate.

In addition, several ongoing studies are looking at combinations with PARP inhibitors "to try to expand who may benefit or lengthen how long they may work," Litton said.The trial results are preliminary, as talazoparib has not yet been approved by the U.S. Food and Drug Administration.

In January, the FDA approved the first PARP inhibitor, Lynparza, to treat BRCA-mutated breast cancer.

Similar drugs have already been used to treat advanced, BRCA-mutated ovarian cancer, according to the agency.

In the current trial, the women who were randomly selected to receive talazoparib had a higher response rate to treatment than women who received standard chemotherapy: 63 percent versus 27 percent, the researchers found.

The drug does have side effects. Among women receiving talazoparib, 55 percent had blood disorders, mostly anemia, compared with 38 percent of those receiving standard chemotherapy.

In addition, 32 percent of the women receiving talazoparib had other side effects, compared with 38 percent of those on standard chemotherapy.

Oncologist Dr. Marisa Weiss is the founder and chief medical officer of Breastcancer.org. "Smart medicines like this PARP inhibitor work better than traditional chemo in women with HER2-negative metastatic disease and a BRCA1/2 genetic mutation," she said.

This targeted form of treatment takes advantage of a weakness in the BRCA gene to further cripple the cancer cell's ability to repair itself, grow and spread, said Weiss, who was not involved with the study.

Normal cells are mostly spared. As a result, more cancer cells are killed with fewer side effects, Weiss said.

"Most importantly, patients themselves have reported a better experience with less hair loss and improved quality of life," she said.

Weiss advises women with advanced breast cancer to have genetic testing.

"In both my clinical practice and within the online support community, we advise women with metastatic breast cancer to get genetic testing upon diagnosis, in order to get the best care first," she said.

The trial was funded by drug maker Pfizer, and the results were published Aug. 15 in the New England Journal of Medicine.

https://www.nejm.org/doi/full/10.1056/NEJMoa1802905

Ref : https://en.wikipedia.org/wiki/Talazoparib

Nusinersen (Spinraza) for Spinal Muscular Atrophy May Help Older Children

 A drug used to treat a rare and deadly muscle-wasting disease in children still improves muscle control even if treatment begins at a later age, a new study found.

Spinal muscular atrophy (SMA) is a leading genetic cause of death in infants worldwide. It attacks nerve cells in the spinal cord, leading to muscle weakness, which can affect breathing, swallowing, walking and head control.

SMA type 1 is the most common and severe form of the disease. It starts before 6 months of age, with infants never gaining the ability to sit up. The median survival rate is eight to 14 months. That means half have shorter lives, half longer.

Previous studies focused on children 7 months old or younger.

This new study included 33 children, ages 8 months to 8 years, with SMA type 1. They were given an injection of the drug nusinersen (Spinraza) into the spinal canal.

The drug increases production of a protein essential for motor neurons in the spinal cord to survive. It was approved by the U.S. Food and Drug Administration in December 2016, and is the first and only approved treatment for all types of SMA.

Six months after the injection, all 33 children had significant muscle control improvements, even the oldest, the researchers reported.

Five patients, ranging from 18 months to 4 years of age when they got their first injection, were able to sit up without support for the first time.

The study was published Aug. 29 in the online issue of the journal Neurology.

"This study is exciting because we found participants had motor function improvement six months after receiving treatment, even an 8-year-old participant," study author Dr. Laurent Servais said in a journal news release.

Servais is a pediatric neurologist at Pitie-Salpetriere Hospital in Paris, France, and Citadelle Hospital in Liege, Belgium.

"The overall response was to the same extent as that in the previously studied younger population," he noted.

"Spinal muscular atrophy type 1 is a devastating disease, and it is encouraging to see that nusinersen may also help people who are at a later stage in the disease process," Servais said.

More research is needed, he said, to find out if genetic factors affect differences in patients' response to treatment.

Ref : https://en.wikipedia.org/wiki/Nusinersen