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

Unapproved Drug, Ibudilast, Slows Brain Shrinkage in Progressive MS

A drug that has long been used in Japan for asthma may slow down brain shrinkage in people with progressive multiple sclerosis, a preliminary trial has found.

The study, published Aug. 30 in the New England Journal of Medicine, tested an oral drug called ibudilast. It is not approved in the United States, but has been used for years in Japan as a treatment for asthma and for vertigo in stroke survivors.

Researchers found that the drug slowed brain shrinkage by 48 percent when compared with an inactive placebo among patients with progressive MS.

Multiple sclerosis is a neurological disorder caused by a misguided immune system attack on the protective sheath around nerve fibers in the spine and brain. Depending on where the damage occurs, symptoms include vision problems, muscle weakness, numbness, and difficulty with balance and coordination.

Most people with MS are initially diagnosed with the "relapsing-remitting" form, meaning that their symptoms flare up for a time and then ease.

Patients in this trial had progressive MS, where the disease steadily worsens without periods of recovery.

And while more than a dozen drugs are available to manage relapsing MS, there are few options for progressive forms of the disease, said Dr. Robert Fox, lead researcher on the new study.

In general, the drugs for relapsing MS do not work for people with progressive forms, said Fox, a neurologist at the Cleveland Clinic.

The biology of progressive MS, Fox explained, seems to be "fundamentally different." Inflammation drives relapsing MS, while the progressive forms seem to be driven by degeneration of nerve cells in the brain, following damage from the inflammatory phase.

Ibudilast can suppress inflammation, and it was first tested against relapsing MS -- where it failed to prevent relapses. But, Fox said, the drug did slow brain shrinkage (atrophy). And that led researchers to suspect it might help patients with progressive MS.

Fox and his colleagues recruited 255 patients with progressive MS from 28 U.S. medical centers. Patients were randomly assigned to take either ibudilast or placebo pills every day for 96 weeks.

In the end, patients on the drug showed, on average, 48 percent less atrophy in their brain tissue.

The big question, Fox said, is whether that will slow patients' progression to disability.

"This is a proof-of-concept," he said. "We've shown that this slows brain atrophy. We haven't shown that it slows clinical progression."

Longer-term studies are needed to prove that. For now, Fox stressed, "this drug is not available in the U.S., and it will be some time before it is."

Bruce Bebo is executive vice president of research for the National Multiple Sclerosis Society -- which partly funded the trial.

Bebo called the findings a "milestone," but cautioned that the drug will have to show benefits against the disease's course, and not only brain shrinkage."Those clinical benefits take a longer time to measure," he said. For patients and families, though, this is one more positive step against progressive MS, he added."This is one of a number of trials testing new therapies for progressive MS," Bebo said. "It's only a matter of time before we'll have more and better treatments."Ibudilast did have side effects: 92 percent of patients in the trial reported "adverse events," though 88 percent of placebo patients did, too. Headaches and gastrointestinal symptoms -- like abdominal pain and nausea -- were the main problems tied to the drug.In addition, 9 percent of ibudilast patients developed depression, compared to 3 percent of placebo patients.Fox said, "That's something we'll want to watch very carefully going forward."But overall, only 8 percent of ibudilast patients withdrew from the study because of a side effect. That suggests the drug was well-tolerated, Fox said.

There are two forms of progressive MS: secondary, which develops after an initial diagnosis of relapsing MS; and primary, which means it progressively worsens from the start, with no periods of remission.

About half of Americans with MS have a progressive form of the disease, according to Bebo.

Yet, Fox said, they've been "underserved" when it comes to research into new treatments."Progressive MS has been the forgotten child," Fox said. "I think this study can provide them with another chapter of hope."

FDA Approves Merck’s Pifeltro (doravirine) for the Treatment of HIV-1 in Appropriate Patients

Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced that the U.S. Food and Drug Administration (FDA) has approved Pifeltro (doravirine, 100 mg), a new non-nucleoside reverse transcriptase inhibitor (NNRTI) to be administered in combination with other antiretroviral medicines. Pifeltro is indicated for the treatment of HIV-1 infection in adult patients with no prior antiretroviral treatment experience, and is administered orally once daily with or without food. Pifeltro does not cure HIV-1 infection or AIDS.

The FDA also approved Delstrigo, a once-daily fixed-dose combination tablet of doravirine (100 mg), lamivudine (3TC, 300 mg) and tenofovir disoproxil fumarate (TDF, 300 mg).

Pifeltro is contraindicated when co-administered with drugs that are strong cytochrome P450 (CYP)3A enzyme inducers as significant decreases in doravirine plasma concentrations may occur, which may decrease the effectiveness of Pifeltro.

FDA Approves Merck’s Pifeltro (doravirine) for the Treatment of HIV-1 in Appropriate Patients

Merck,  known as MSD outside the United States and Canada,  announced that the U.S. Food and Drug Administration (FDA) has approved Pifeltro (doravirine, 100 mg), a new non-nucleoside reverse transcriptase inhibitor (NNRTI) to be administered in combination with other antiretroviral medicines. Pifeltro is indicated for the treatment of HIV-1 infection in adult patients with no prior antiretroviral treatment experience, and is administered orally once daily with or without food. Pifeltro does not cure HIV-1 infection or AIDS.

The FDA also approved Delstrigo, a once-daily fixed-dose combination tablet of doravirine (100 mg), lamivudine (3TC, 300 mg) and tenofovir disoproxil fumarate (TDF, 300 mg).

Pifeltro is contraindicated when co-administered with drugs that are strong cytochrome P450 (CYP)3A enzyme inducers as significant decreases in doravirine plasma concentrations may occur, which may decrease the effectiveness of Pifeltro.

FDA Approves Merck’s Delstrigo (doravirine/lamivudine/tenofovir disoproxil fumarate) for the Treatment of HIV-1 in Appropriate Patients

In continuation of my update on Lamivudine and Tenofovir


    




doravirine                                 Lamivudine                                             Tenofovir

Merck  known as MSD outside the United States and Canada, announced that the U.S. Food and Drug Administration (FDA) has approved Delstrigo, a once-daily fixed-dose combination tablet of doravirine (100 mg), lamivudine (3TC, 300 mg) and tenofovir disoproxil fumarate (TDF, 300 mg) for the treatment of HIV-1 infection in adult patients with no prior antiretroviral treatment experience. Delstrigo is administered orally once daily with or without food. Delstrigo contains a boxed warning regarding post-treatment acute exacerbation of hepatitis B (HBV) infection. Delstrigo does not cure HIV-1 infection or AIDS.

The FDA also approved Pifeltro (doravirine, 100 mg), the new non-nucleoside reverse transcriptase inhibitor (NNRTI) contained in Delstrigo, for administration in combination with other antiretroviral medicines.

Delstrigo is contraindicated when co-administered with drugs that are strong cytochrome P450 (CYP)3A enzyme inducers as significant decreases in doravirine plasma concentrations may occur, which may decrease the effectiveness of Delstrigo. Delstrigo is contraindicated in patients with a previous hypersensitivity reaction to 3TC. For more information, see “Selected Safety Information” below.

Immune reconstitution syndrome can occur, including the occurrence of autoimmune disorders with variable time to onset, which may necessitate further evaluation and treatment. Renal impairment, including cases of acute renal failure and Fanconi syndrome, have been reported with the use of TDF. Delstrigo should be avoided with concurrent or recent use of a nephrotoxic agent, as cases of acute renal failure after initiation of high-dose or multiple non-steroidal anti-inflammatory drugs (NSAIDs) have been reported in patients with risk factors for renal dysfunction who appeared stable on TDF.

Data Supporting the Approval of Delstrigo (doravirine 100 mg/3TC 300 mg/TDF 300 mg)

The FDA approvals of Delstrigo and Pifeltro are based on findings from the pivotal, randomized, multicenter, double-blind, active controlled Phase 3 trials, DRIVE-AHEAD and DRIVE-FORWARD, evaluating the efficacy and safety of Delstrigo and Pifeltro, respectively, in participants infected with HIV-1 with no antiretroviral treatment history.

FDA Approves Merck’s Delstrigo (doravirine/lamivudine/tenofovir disoproxil fumarate) for the Treatment of HIV-1 in Appropriate Patients

In continuation of my update on Imbruvica (ibrutinib)

The Janssen Pharmaceutical Companies of Johnson & Johnson today announced the U.S. Food and Drug Administration (FDA) approval of Imbruvica (ibrutinib) in combination with rituximab for the treatment of Waldenström’s macroglobulinemia (WM), a rare blood cancer.[1] The approval expands the label for Imbruvica in WM beyond its current approved use as a monotherapy to include combination use with rituximab. This approval represents the first approved non-chemotherapy combination option for the treatment of WM. Imbruvica first received FDA approval in WM as a monotherapy in January 2015 via the Breakthrough Therapy Designation pathway, making it the first FDA-approved therapy for the disease. The expanded label marks the ninth FDA approval for Imbruvica since 2013. Imbruvica is a first-in-class Bruton's tyrosine kinase (BTK) inhibitor jointly developed and commercialized by Janssen Biotech, Inc. and Pharmacyclics LLC, an AbbVie company.

The combination of Imbruvica and rituximab provides health care professionals with a new treatment option for patients living with this serious blood cancer,” said Dr. Lia Palomba, hematologist-oncologist at Memorial Sloan-Kettering Cancer Center, New York, and iNNOVATE study investigator. “Before Imbruvica, there were no FDA-approved treatment options for patients with Waldenström’s macroglobulinemia, a disease first acknowledged nearly 75 years ago. Today, Imbruvica continues to provide an important therapeutic approach in the treatment of this complex disease.”

This approval is based on results from the randomized, double-blind, placebo-controlled iNNOVATE study (PCYC-1127), the largest Phase 3 study of a non-chemotherapy combination in WM patients. The iNNOVATE study evaluated Imbruvica in combination with rituximab versus placebo plus rituximab in 150 patients with either relapsed/refractory (r/r) disease or previously untreated WM. At a median follow up of 26.5 months, a significant improvement in the Independent Review Committee (IRC)-assessed primary endpoint of progression-free survival (PFS) was seen with Imbruvica plus rituximab when compared with placebo plus rituximab (30-month PFS rates were 82% vs. 28%, respectively). Patients in the Imbruvica plus rituximab treatment arm experienced an 80% reduction in relative risk of disease progression or death compared with patients treated with placebo plus rituximab (hazard ratio=0.20; confidence interval, 0.11-0.38, p<0.0001). The data were presented in an oral session at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, selected for Best of ASCO 2018 Meetings, and simultaneously published in The New England Journal of Medicine.

“Results from iNNOVATE showed significant improvement in progression-free survival at 30 months and demonstrated the superiority of Imbruvica plus rituximab over rituximab monotherapy in Waldenström's macroglobulinemia,” said Meletios A. Dimopoulos, M.D., Professor and Chairman of the Department of Clinical Therapeutics, National and Kapodistrian University of Athens School of Medicine, Athens, Greece, and iNNOVATE lead study investigator. “Based on these results, Imbruvica in combination with rituximab may be considered as a first- and second-line option for appropriate people diagnosed and living with WM.”

“The clinical data generated for Imbruvica plus rituximab in the treatment of Waldenström’s macroglobulinemia offers physicians evidence to consider this combination regimen for newly-diagnosed patients. Today’s approval represents an important milestone for people living with this rare and incurable blood cancer who have limited FDA-approved treatment options,” said Andree Amelsberg, M.D., Vice President of Oncology Medical Affairs at Janssen Scientific Affairs, LLC. “We remain dedicated to a comprehensive clinical development program to explore the full potential of Imbruvica, including in combination with other therapies.”

Warnings and Precautions remain the same: hemorrhage, infections, cytopenias, cardiac arrhythmias, hypertension, second primary malignancies, tumor lysis syndrome, and embryo-fetal toxicity. The most common adverse reactions (occurring in 20% or more of patients) of all grades in patients treated with Imbruvica plus rituximab in the iNNOVATE study were bruising (37%), musculoskeletal pain (35%), hemorrhage (32%), diarrhea (28%), rash (24%), arthralgia (24%), nausea (21%), and hypertension (20%). Grade 3 or 4 infusion-related reactions were observed in 1% of patients treated with Imbruvica plus rituximab.

The recommended dose of Imbruvica for WM is 420 mg orally once daily until disease progression or unacceptable toxicity as a single agent or in combination with rituximab. When administering Imbruvica in combination with rituximab, consider administering Imbruvica prior to rituximab when given on the same day.

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

Sunovion receives Complete Response Letter from FDA for dasotraline NDA

Sunovion Pharmaceuticals Inc. (Sunovion) today announced that the U.S. Food and Drug Administration (FDA) issued a Complete Response Letter for the New Drug Application (NDA) for dasotraline, a novel dual-acting dopamine and norepinephrine reuptake inhibitor (DNRI), for the treatment of attention-deficit hyperactivity disorder (ADHD).

Upon completion of their review, the FDA determined that they cannot approve the dasotraline NDA for the treatment of ADHD in its current form. The Agency indicated that additional clinical data are needed to further evaluate the efficacy and tolerability of dasotraline for the treatment of ADHD. Sunovion plans to meet with the FDA to discuss their comments and determine next steps.

Dasotraline was evaluated in approximately 2,500 children and adults with ADHD in multiple placebo-controlled safety and efficacy studies, as well as two long-term safety studies.

"While we are disappointed with the FDA's decision, we remain confident in the future of dasotraline," said Antony Loebel, M.D., Executive Vice President and Chief Medical Officer at Sunovion, Head of Global Clinical Development for Sumitomo Dainippon Pharma Group. "We plan to discuss next steps for the dasotraline ADHD program with the FDA as soon as possible."

Dasotraline is also being studied for the treatment of moderate to severe binge eating disorder (BED) in adults in the U.S. Data from two positive pivotal studies will support an expected marketing application submission to the FDA for dasotraline to treat BED in FY2018.​

Ref : https://news.sunovion.com/press-release/fda-issues-complete-response-letter-new-drug-application-dasotraline-treatment-adhd

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

Ketamine’s role in treatment of depression: Study

In continuation of my update on Ketamine

The anaesthetic drug Ketamine has been shown to be beneficial in some cases of depression and suicidal ideation which have typically failed to respond to other standard antidepressant medications. A new study has explored the actual workings of ketamine in depression and found that the drug can act on the same receptors as opioid pain relievers.

The latest study was published in the American Journal of Psychiatry.

For this the researchers from the Stanford’s Neurosciences Institute included 12 volunteers at first. These cases were all of treatment-resistant depression.

The participants were all given infusion of Ketamine. In addition some were administered naltrexone and others normal saline infusion. Naltrexone is a drug that can block the effects of opioids.

Results showed that those on ketamine and saline combination found relief from their depressive symptoms quickly compared to those on ketamine and naltrexone combination. In fact those on ketamine and saline placebo reported at least a 90 percent reduction in their symptoms within the first three days of the infusion.

No such improvement was seen among those on ketamine and naltrexone. This proved that when the opioid actions are blocked, the ketamine cannot function as an antidepressant. Both groups faced certain side effects of ketamine such as an “out-of-the-body” experience, dysphoric feelings, tripping etc. This also showed that the antidepressant action of Ketamine was separate from its usual actions, which were seen in all participants in either group.

The initial trial plan was to include 30 patients. Due to the dramatic improvement seen in one group and no changes in the other, the team decided to stop the trial prematurely. This was to spare patients useless treatment.

Ketamine has been in news recently due to its unexplored potential as an antidepressant. If proven, researchers believe, this could impact depression research significantly. Ketamine has gathered interest mainly because it does not change the brain chemistry unlike other antidepressants. Co-author Boris Heifets, a clinical assistant professor of anesthesiology, perioperative and pain medicine at Stanford explained that ketamine blocks the brain’s receptors for glutamate. Glutamate is an important neurotransmitter in the brain. Many researchers have thought that glutamate could be the key zone where ketamine acts as an antidepressant. Heifets added that ketamine is not a simple drug and has varied targets which could be responsible for its antidepressant activities. A lot of money has been spent on developing agents that could work on the glutamate receptors and try to mimic ketamine’s antidepressant actions.

This study shows that the approach is incorrect and glutamates are not the target lead author Nolan Williams explained. Co-senior study author Dr. Alan Schatzberg, a professor of psychiatry and behavioral sciences at Stanford explained that the ketamine was not working as “everyone thought it was working.”

Heifets noted that ketamine is a drug of abuse (called “Special K” in party circuits) that has been in use for a long time and there is an abuse potential of this drug acting on the opioid receptors to provide such effects. He warned that this abuse potential should be kept in mind before ketamine comes into the market as an antidepressant.

However the whole team agrees that this new study shows how ketamine can help patients who have intractable depression. New drugs could be developed in the same lines they explain. These drugs could possibly activate the opioid receptors without having abuse potential they add. Williams added that ketamine has been seen to provide relief of symptoms in other mental ailments such as obsessive compulsive disorders and now is the time to explore if opioids play a role in these diseases as well.

Mark George, a professor of psychiatry, radiology and neuroscience at the Medical University of South Carolina in an editorial accompanying the article wrote that this study is a small one and so should be confirmed in larger trials before conclusions could be drawn.

Ref : https://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2018.18020138

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

Eat one avocado per day for six months and get paid, weight loss study

In continuation of my update on Avocado

A latest weight loss study from the Loma Linda University is looking for participants to consume avocados for them and get paid for it too. The study is to be called, “The Habitual Diet and Avocado Trial.”

Joan Sabaté, MD, PhD, lead author and director of the university's Center for Nutrition, Lifestyle and Disease Prevention, said in an online statement, “The study will examine whether eating one avocado per day reduces visceral adipose fat in the abdomen.” The team is calling out to men and women over the age of 25 years who have waist measurements of 40 and 35 inches or more respectively. The rules add that all participants must be willing to “eat one avocado per day for six months or eat only two avocados per month for the same period”. Pregnant and breastfeeding women and those who are planning to get pregnant would not be included in the study.

The rules for participating in the study state that the participants would be divided into two groups –

• The test group would be “given 16 avocados every two weeks and required to eat one avocado per day throughout the six-month study.”
• The control group on the other hand, “will be required to eat no more than two avocados per month during the same period.”

During the course of the study, all participants would be given free health screening and MRI scans and they would need to need each month with their dietician. Participants of both groups would be paid $300 each on completion of the study. They, in addition would be given 24 avocados.

Avocados are known to be rich in fats that are good for the heart. They can help control cholesterol and promote health. However some studies have contradicted the value of avocados in daily diet. Loma Linda University statement reads, “Since avocados contain the highest fat content of any fruit, it seems illogical to think they might actually help people lose their belly fat.” This study would examine if consuming one avocado per day can help reduce the abdominal fat.

At present the study is calling for 1000 participants from not only the Loma Linda University but also from the Tufts University, Penn State University and the University of California, Los Angeles. These would recruit 250 more participants each for the study. Once the study is complete, the data from the participants would be analyzed by the Wake Forest University.

Ref : https://hhd.psu.edu/nutrition/research/research-labs-and-initiatives/cardiometabolic-nutrition-research-lab/avocado-study

Low carbohydrate diet can increase risk of premature death, finds study

Low carbohydrate diets are unsafe and should be avoided, according to a large study presented today at ESC Congress 2018.

Study author Professor Maciej Banach, of the Medical University of Lodz, Poland, said: "We found that people who consumed a low carbohydrate diet were at greater risk of premature death. Risks were also increased for individual causes of death including coronary heart disease, stroke, and cancer. These diets should be avoided."

Obesity is a major health issue worldwide and raises the risk of several chronic conditions, including cardiovascular disease, hypertension, type 2 diabetes, and cancer. Different diets have been suggested for weight loss, such as diets low in carbohydrates and high in protein and fat. The long-term safety of these diets is controversial, with previous studies reporting conflicting results of their influence on the risk of cardiovascular disease, cancer, and death.

This study prospectively examined the relationship between low carbohydrate diets, all-cause death, and deaths from coronary heart disease, cerebrovascular disease (including stroke), and cancer in a nationally representative sample of 24,825 participants of the US National Health and Nutrition Examination Survey (NHANES) during 1999 to 2010. Compared to participants with the highest carbohydrate consumption, those with the lowest intake had a 32% higher risk of all-cause death over an average 6.4-year follow-up. In addition, risks of death from coronary heart disease, cerebrovascular disease, and cancer were increased by 51%, 50%, and 35%, respectively.

The results were confirmed in a meta-analysis of seven prospective cohort studies with 447,506 participants and an average follow-up 15.6 years, which found 15%, 13%, and 8% increased risks in total, cardiovascular, and cancer mortality with low (compared to high) carbohydrate diets (see figure for total mortality).

Professor Banach said: "Low carbohydrate diets might be useful in the short term to lose weight, lower blood pressure, and improve blood glucose control, but our study suggests that in the long-term they are linked with an increased risk of death from any cause, and deaths due to cardiovascular disease, cerebrovascular disease, and cancer."

Participants in the NHANES study had an average age of 47.6 years, and 51% were women. They were divided into quartiles based on the usual percentage of carbohydrates in their diet. The risks of all-cause and cause-specific death over an average 6.4-year follow-up rose with each fall in carbohydrate intake (see table), and remained significant after adjusting for all available factors that might have influenced the association (model 2 in the table).

The researchers also examined the link between all-cause death and low carbohydrate diets for obese (body mass index [BMI] 30 kg/m2 or greater) and non-obese (BMI under 30 kg/m2) participants in two age groups (55 years and older versus under 55) and found that the link was strongest in the non-obese older participants.

Low carbohydrate diet can increase risk of premature death, finds study