FDA approves esketamine nasal spray for refractory depression


  • The FDA has approved esketamine nasal spray, Spravato (Janssen Pharmaceuticals), for treatment-resistant depression.

Why this matters

Key highlights

  • Indication is for adults with depression for whom ≥2 other antidepressant medications have failed.
  • It is to be taken with an oral antidepressant.
  • A black box warning accompanies approval because of serious adverse event risk, including for sedation, abuse, and suicidal thoughts and behaviors.
  • The spray is also subject to restricted distribution under a Risk Evaluation and Mitigation Strategy (REMS):
    • REMS requirements include patient commitment not to drive or use heavy machinery on the day of administration.
    • Health care providers are to monitor patients for 2 hours after self-administration of the spray, which cannot be taken home.
  • Supporting evidence:
    • Short-term placebo-controlled trial: effect was detected within 2 days in some cases.
    • Results of 2 other short-term trials did not meet threshold for statistical effect.
    • Long-term trial suggested stable remission or response, latency to relapse with treatment.
  • Side-effects include dissociation, dizziness, increased BP, feeling inebriated.
  • Spray is contraindicated in pregnancy and with breastfeeding and may increase risk for vascular events in patients with existing disease.

U.S. FDA Approves New Protocol for Study on Bayer’s Essure Birth Control Device

The U.S. Food and Drug Administration on Thursday approved a new protocol for a post-marketing study of Bayer AG’s Essure birth-control device, as the regulator seeks more information on the device’s safety.

The study would now monitor women implanted with the devices for five years, up from three years, and would need additional blood tests.

The company faces several lawsuits over Essure in the United States.

Women have claimed in lawsuits that the device, which is implanted in a woman’s fallopian tubes to permanently block the passage of eggs to the uterus, could pierce the tubes, and that the device’s metal parts could become dislodged and migrate to other parts of the body.

Bayer said in July it would phase out the birth control product in the United States, a decision which the company said was due to declining sales of the implantable device and not based on safety concerns.

FDA Clears Test to Analyze Nutrients in Breast Milk

The US Food and Drug Administration (FDA) has cleared for marketing a diagnostic test to measure nutrients in breast milk, including the concentration of fat, carbohydrates, protein, total solids, and energy.

The Miris Human Milk Analyzer

The Miris Human Milk Analyzer (Miris AB) can help with nutritional management of newborns and young infants at risk for growth failure due to prematurity or other medical conditions. Knowing the macronutrient content of the breast milk may help clinicians make informed decisions on how to fortify the breast milk based on the individual needs of the infant, the FDA explained in a news release.

“For the first time, doctors have access to a test to help analyze the nutrients in breast milk. While this test is not for everyone, it has the potential to aid parents and healthcare providers, mainly in a hospital setting, in better assessing the nutrient needs of certain babies who are not growing as expected,” Courtney Lias, PhD, director of the Division of Chemistry and Toxicology Devices in the FDA’s Center for Devices and Radiological Health, said in the release.

The Miris Human Milk Analyzer uses an infrared spectroscopy system to analyze human milk and provide a quantitative measurement of fat, protein, and total carbohydrate content. It can also calculate the total solids and energy content of the milk. It is intended for use by trained personnel in clinical laboratories.

The accuracy of the Miris analyzer was demonstrated in an FDA analysis of 112 samples of human milk tested by the Miris analyzer and by independent methods. Both methods were similarly effective at determining levels of protein, fat, and carbohydrates in the milk.

However, the FDA said certain medications that a nursing mother may be taking could interfere with the test’s ability to accurately measure nutrient levels in breast milk.

The agency advises healthcare providers to carefully evaluate the Miris Human Milk Analyzer test results in conjunction with clinical assessments (such as weight and growth) when creating a nutritional management plan for an infant.

The FDA reviewed the Miris Human Milk Analyzer test through the de novo premarket review pathway, a regulatory pathway for some new types of low- to moderate-risk devices.

Along with this marketing authorization, the FDA is establishing “special controls” that set forth the agency’s expectations in ensuring the accuracy, reliability, and effectiveness of tests intended to measure the nutritional content of human milk to aid in the nutritional management of certain infants.

“These special controls, when met along with general controls, provide a reasonable assurance of safety and effectiveness for tests of this type,” the agency said.

FDA Approves New Treatment for Patients With Acute Myeloid Leukemia

The U.S. Food and Drug Administration today approved Daurismo (glasdegib) tablets to be used in combination with low-dose cytarabine (LDAC), a type of chemotherapy, for the treatment of newly-diagnosed acute myeloid leukemia (AML) in adults who are 75 years of age or older or who have other chronic health conditions or diseases (comorbidities) that may preclude the use of intensive chemotherapy.

“Intensive chemotherapy is usually used to control AML, but many adults with AML are unable to have intensive chemotherapy because of its toxicities. Today’s approval gives health care providers another tool to use in the treatment of AML patients with various, unique needs. Clinical trials showed that overall survival was improved using Daurismo in combination with LDAC compared to LDAC alone for patients who would not tolerate intensive chemotherapy,” said Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.

AML is a rapidly progressing cancer that forms in the bone marrow and results in an increased number of abnormal white blood cells in the bloodstream and bone marrow. The National Cancer Institute at the National Institutes of Health estimates that in 2018, approximately 19,520 people will be diagnosed with AML and approximately 10,670 patients with AML will die of the disease. Almost half of the adults diagnosed with AML are not treated with intensive chemotherapy because of comorbidities and chemotherapy related toxicities.

The efficacy of Daurismo was studied in a randomized clinical trial in which 111 adult patients with newly diagnosed AML were treated with either Daurismo in combination with LDAC or LDAC alone. The trial measured overall survival (OS) from the date of randomization to death from any cause. Results demonstrated a significant improvement in OS in patients treated with Daurismo. The median OS was 8.3 months for patients treated with Daurismo plus LDAC compared with 4.3 months for patients treated with LDAC only.

Common side effects reported by patients receiving Daurismo in clinical trials include low red blood cell count (anemia), tiredness (fatigue), bleeding (hemorrhage), fever with low white blood cell count (febrile neutropenia), muscle pain, nausea, swelling of the arms or legs (edema), low platelet counts (thrombocytopenia), shortness of breath (dyspnea), decreased appetite, distorted taste (dysgeusia), pain or sores in the mouth or throat (mucositis), constipation and rash.

The prescribing information for Daurismo includes a Boxed Warning to advise health care professionals and patients about the risk of embryo-fetal death or severe birth defects. Daurismo should not be used during pregnancy or while breastfeeding. Pregnancy testing should be conducted in females of reproductive age prior to initiation of Daurismo treatment and effective contraception should be used during treatment and for at least 30 days after the last dose. The Boxed Warning also advises male patients of the potential risk of drug exposure through semen and to use condoms with a pregnant partner or a female partner that could become pregnant both during treatment and for at least 30 days after the last dose. Daurismo must be dispensed with a patient Medication Guide that describes important information about the drug’s uses and risks. Patients should also be advised not to donate blood or blood products during treatment. Health care providers should also monitor patients for changes in the electrical activity of the heart, called QT prolongation.

The FDA granted this application Priority Review designation. Daurismo also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.

The FDA granted the approval of Daurismo to Pfizer.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

First DTC Test for Some BRCA Mutations Authorized by FDA

The US Food and Drug Administration (FDA) has authorized the use of a direct-to-consumer (DTC) test for BRCA1/2 mutations. While it is not the first DTC genetic test to enter the US marketplace, this is the first one to test specifically BRCA mutations.

The new test is the Personal Genome Service Genetic Health Risk (GHR) Report for BRCA1/BRCA2 (Selected Variants), from the company 23andMe.

However, the scope of the test is limited because it can test for only three genetic variants out of more than 1000 known BRCA mutations. The three genetic mutations covered by the test are the most common ones found in Ashkenazi (East European) Jews, but they are not the most common BRCA1/2 mutations found in the general population, the agency explains.

Therefore, while a positive test result will alert individuals to an increased cancer risk, a negative result can be falsely reassuring. Because it tests for only three mutations, a negative result does not rule out the possibility that an individual may be carrying other BRCA mutations that elevate cancer risk.

“This test provides information to certain individuals who may be at increased breast, ovarian or prostate cancer risk and who might not otherwise get genetic screening, and is a step forward in the availability of DTC genetic tests,” said Donald St. Pierre, acting director of the Office of In Vitro Diagnostics and Radiological Health in the FDA’s Center for Devices and Radiological Health, in a statement.

But he added that there are a lot of caveats. “While the detection of a BRCA mutation on this test does indicate an increased risk, only a small percentage of Americans carry one of these three mutations and most BRCA mutations that increase an individual’s risk are not detected by this test,” he explained.

Katie Watson, a spokesperson for 23andme, reiterated that the test does not include most of the BRCA1 and BRCA2 variants found in people who are not Ashkenazi Jews. Therefore, a “variant not detected” result is far less informative for people with no Ashkenazi Jewish ancestry.

However, a “variant detected” result is still informative for other populations, she pointed out. “The effect of BRCA1 and BRCA2 variants on a person’s risk of developing breast, ovarian, prostate, and other cancers is well understood in people of many different ethnicities,” Watson said. “So if a woman has one or more of these genetic variants but is not of Ashkenazi Jewish descent, she still has a greatly increased risk of developing breast and ovarian cancer.  And men of other ethnicities who have a variant still have an increased risk of developing male breast cancer and, in some cases, prostate cancer.”

About 1 in 40 people of Ashkenazi Jewish ancestry have a deleterious BRCA mutation compared with about 1 in 400 people in the general population. The three variants included in this test account for over 90% of these BRCA1 and BRCA2 variants found in the Ashkenazi Jewish population.

Watson emphasized that a negative test result (“no variants detected”) does not significantly reduce one’s cancer risk because other genetic and nongenetic factors not tested here still play a large role in overall risk for these cancers. “However, a positive result is very informative and may significantly increase one’s genetic risk for certain cancers, especially breast and ovarian cancer,” Watson told Medscape Medical News.

“But we also make it very clear that the 23andme test does not describe a person’s overall risk of developing breast, ovarian, or prostate cancer or test for all possible variants in the BRCA1 and BRCA2 genes. Most BRCA1 and BRCA2 variants linked to hereditary cancers are not included in this test or test for variants in other genes linked to hereditary cancers,” Watson added.

Ramping Up Genetic Counseling

The number of women seeking genetic testing for BRCA gene mutations has steadily increased over the past decade. According to one recent study, which examined private insurance claims for BRCA mutation testing between 2004 and 2014, testing increased from 24.3% to 61.5%.

But despite the more than twofold increase in testing, most women are not getting genetic counseling — even though guidelines stress its importance. A study conducted in 2015 found that among 3628 women who underwent comprehensive BRCA testing that was ordered by their physicians, only 36.8% of the women (n = 1334) reported receiving genetic counseling from a genetics professional. Patients of obstetricians and gynecologists had the lowest rates of referral (n = 130 women [12.3%]).

Company Also Sells Reports

Watson explained that the company does provide information on why a customer may wish to engage in genetic counseling and how to contact local genetic counselors, which can be found in reports on the company website. “We believe people should have the choice to access their genetic information, and that’s always been core to our mission,” she said. “If a customer decides to view these particular reports, they will be provided with information about resources that may be helpful, including support groups, genetic counseling, and how to discuss results with family.”

The BRCA1/BRCA2 report will be part of the broader 23andMe Health + Ancestry service that includes more than 75 reports on health, wellness, traits, and ancestry, Watson explained, and this service costs $199. “New and existing 23andMe Health + Ancestry Service customers who were genotyped on the company’s most recent platforms will have access to this report in the coming weeks,” she said. “There will be no additional cost for the BRCA report for new or existing customers.”

Watson also pointed out that their test has a high level of accuracy. “The analytical testing of our genotyping process and our ability to correctly identify each of the variants in these reports met predetermined accuracy thresholds, per the FDA review process,” she said. “As with our other FDA-reviewed reports, we again demonstrated greater than 99% concordance as compared to Sanger sequencing, which is considered the gold standard for analyzing DNA. It also showed greater than 99% reproducibility and repeatability.”

The FDA concurs — they have determined that the company provided sufficient data to show that the test is accurate and can provide reproducible results. “The company submitted data on user comprehension studies, using representative GHR test reports, that showed instructions and reports were generally easy to follow and understood by a consumer,” the agency said in a press release. “The test report provides information describing what the results might mean, how to interpret results and where additional information about the results may be found.”

Target Audience

Despite its limitations, DTC testing could be a convenient and low-cost option for individuals who do not meet the current criteria for BRCA screening or who find that there are too many restrictions and barriers. For example, while genetic counseling is recommended, some insurance companies are now requiring that women be advised by a certified genetic counselor or someone with similar training before a genetic test can be ordered. The American Congress of Obstetricians and Gynecologists has opposed this restriction, warning that it places an unnecessary burden on the patient and could limit access to care.

In addition, large studies conducted in Canada, Israel, and the United Kingdom have indicated that more than half of Ashkenazi women who carry the mutation do not qualify for genetic testing on the basis of family history. Most young women with breast cancer do not have a family history of breast or ovarian cancer or Ashkenazi Jewish ancestry and therefore would also be ineligible for BRCA mutation testing before a cancer diagnosis.

FDA clears New device for retrieving clots up to 24 hrs in Ischaemic Stroke


FDA approves Biktarvy ,a once daily HIV drug


Are MRI-Safe Cardiac Devices Outpacing the FDA?

As safety data accrue, regulatory changes are awaited for this class of ICDs.

  •  Challenging the FDA to keep pace with the advance of so-called “MRI-safe” or “conditional” implantable cardiac defibrillators (ICDs), yet another manufacturer has presented study results showing these devices pose no risk to patients undergoing MRI.

“Regulatory changes are needed to allow for routine MRI in patients with conditional ICDs after proper evaluation by qualified personnel,” Khaled Awad, MD, from the University of Alabama-Birmingham School of Medicine, commented at a press conference during the Heart Rhythm Society’s 36th Annual Scientific Sessions.

Awad’s non-randomized, single-arm results are for an ICD — Biotronik’s Iforia ProMRI ICD System — that is already in clinical use as a standard ICD but with the MRI-safety feature deactivated until it receives FDA approval.

His findings are similar to randomized resultsreported earlier at the meeting for another device that is not FDA-approved, Medtronic’s Evera MRI.

Both studies “further confirm that if you design a system platform specifically for MRI it should perform well in the MRI environment and hopefully it will open the door to a new era where most devices are designed to meet that standard,” said Awad.

The study included 154 patients (mean age 60 years) from 39 U.S. clinical sites who were implanted with the ICD device in the MRI-safe mode.

The MRI-safety mode disables detection and therapy of ventricular arrhythmias and must be turned off after scanning to re-activate the ICD.

After a 5-week waiting period, 148 patients received non-clinically indicated cardiac (25.7%) or thoracic spine (74.3%) 1.5 Tesla MRI scans that were standardized between all centers and “aimed at stressing the device and the whole system as much as possible and increasing the magnitude of the magnetic field to probably the highest one would encounter in a clinical scan,” Awad said.

At both 1- and 3-month follow-up there were no adverse outcomes deemed to be related or possibly related to the ICD system or MRI, no significant increases in ventricular capture threshold, or significant decreases in ventricular sensing.

“We didn’t detect any changes to pacing or sensing parameters, and most importantly there was no impact on the device’s main function which is detecting and treating ventricular arrhythmias. This device platform will allow patients with ICDs to safely undergo MRI in 1.5T scanners for various clinical indications,” he concluded.


The U.S. Food and Drug Administration approved Anthrasil, Anthrax Immune Globulin Intravenous (Human), to treat patients with inhalational anthrax in combination with appropriate antibacterial drugs.

Anthrasil is manufactured from the plasma of individuals vaccinated against anthrax. The plasma contains antibodies that neutralize toxins produced by the anthrax bacteria.

The efficacy of Anthrasil was studied in animals because it was not feasible or ethical to conduct adequately controlled efficacy studies in humans. Rabbits and monkeys were exposed to a lethal aerosolized dose of B. anthracis spores, then treated with Anthrasil or a placebo, and evaluated for survival. Survival in anthrax-infected monkeys treated with Anthrasil ranged from 36 to 70 percent compared to 0 percent survival in the placebo group with a trend toward increased survival at higher doses of Anthrasil. Rabbits treated with a moderate dose of Anthrasil after infection exhibited 26 percent survival compared to 2 percent survival in the placebo group. Another study in rabbits showed that a combination of Anthrasil and antibiotics resulted in 71 percent survival compared to 25 percent survival in animals treated with antibiotics alone.

The results of studies in research animals provided sufficient evidence that Anthrasil is reasonably likely to benefit humans with inhalational anthrax. The FDA’s Animal Rule allows efficacy findings from adequate and well-controlled animal studies to support FDA approval when it is not feasible or ethical to conduct trials in humans.

The safety of the product was tested in 74 healthy human volunteers. The most commonly observed side effects were headache, back pain, nausea and infusion site pain and swelling.

FDA OKs New Infection Drugs

Antibacterial and anti-flu products add to weapons against disease.

A new antibacterial drug and an anti-influenza medication got the nod from the FDA.

The agency approved the combination of ceftolozane, a cephalosporin antibacterial drug, and tazobactam, a beta-lactamase inhibitor, which will be sold as Zerbaxa and used to treat complicated intra-abdominal infections and complicated urinary tract infections.

And it also approved peramivir (Rapivab), an anti-influenza drug delivered by intravenous injection and intended for patients unable to take medication orally or by inhalation.

The approval of ceftolozane/tazobactam is an important milestone, according to the Infectious Diseases Society of America (IDSA), which has been pushing for the development of 10 new systemic antibacterial drugs by 2020.

That campaign — dubbed the 10 x ’20 Initiative — began in 2010, so this approval comes at the halfway mark, the society noted in a statement.

It’s also the fifth new drug since the campaign was launched and the first to address “certain serious and resistant Gram-negative bacteria,” the IDSA statement said.

Zerbaxa’s OK comes in a busy year for antibiotic development. The FDA this year has already approved dalbavancin (Dalvance), tedizolid (Sivextro), and oritavancin (Orbactiv).

The other new antibacterial is ceftaroline fosamil (Teflaro), approved late in 2010.

“The FDA approval of several new antibacterial drugs this year demonstrates the agency’s commitment to increasing the availability of treatment options for patients and physicians,” according to Edward Cox, MD, of the agency’s Center for Drug Evaluation and Research.

“We must continue to help foster the development of new antibacterial drugs and encourage prudent use of existing treatments to conserve their utility,” Cox said in a statement.

On the other hand, the fight is not over, the IDSA said.

“Even this important approval doesn’t address all of our antibiotic needs,” the society statement said. “Patients still face life-threatening infections for which additional new antibiotics are urgently needed.”

Ceftolozane/tazobactam got approval as a qualified infectious disease product under the Generating Antibiotic Incentives Now (GAIN) title of the FDA Safety and Innovation Act as “an antibacterial or antifungal human drug intended to treat a serious or life-threatening infection,” the agency said in a statement.

The combination’s efficacy in complicated intra-abdominal infections (in combination with metronidazole) was established in a clinical trial with 979 adults, randomly assigned to receive the combination plus metronidazole or meropenem.

Efficacy in complicated urinary tract infections was established in a clinical trial where 1,068 adults were randomly assigned to receive the combination or levofloxacin (Levaquin).

The drug’s label notes that efficacy was observed to be lower in patients with renal impairment. The most common side effects in clinical trials were nausea, diarrhea, headache, and fever.

Meanwhile, the agency has also approved peramivir, according to the drug’s maker, BioCryst Pharmaceuticals, of Research Triangle Park, N.C.

The drug is a neuraminidase inhibitor, like oseltamivir (Tamiflu) and zanamivir (Relenza), but given as a single-dose IV shot. Oseltamivir is an oral medication, while zanamivir is inhaled.

Peramivir is intended to be used by adult patients who have uncomplicated flu, but can’t take oral or inhaled drugs. The approved indication specifies that patients must have been symptomatic for no more than 2 days.