The US Food and Drug Administration (FDA) has approved glycopyrrolate inhalation solution 25 mcg twice daily (Lonhala Magnair, Sunovion Pharmaceuticals) for maintenance treatment of airflow obstruction in adults with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema.

Lonhala Magnair is the first nebulized long-acting muscarinic antagonist (LAMA) approved by the FDA for the treatment of COPD. It is the first time the Magnair eFlow technology system, developed by PARI Pharma GmbH, has been used, Sunovion said in a news release.

“This technology is a virtually silent, portable, closed system nebulizer that is designed to deliver the drug in two to three minutes and allows people to breathe normally while using the device,” the company said.

“Despite the availability of several therapies, many people still struggle to control their COPD ― a challenge that may be affected by the delivery method used to administer a medication,” Gary Ferguson, MD, of the Pulmonary Research Institute of Southeast Michigan in Farmington Hills, said in the release.

“Lonhala Magnair offers an important new option that combines the efficacy of a proven medication for COPD with the attributes of a unique handheld nebulizer that allows a person to breathe normally while taking their medication,” Dr Ferguson said.

The approval is based on data from the clinical trials in the GOLDEN (Glycopyrrolate for Obstructive Lung Disease via Electronic Nebulizer) program, which included GOLDEN-3 and GOLDEN-4, two phase 3 randomized, double-blind, placebo-controlled studies in adults with moderate to very severe COPD.

In these studies, individuals using Lonhala Magnair showed “statistically significant and clinically important” changes from baseline in trough forced expiratory volume in 1 second (FEV1) at 12 weeks, the company said.

In addition, the GOLDEN-5 phase 3 study demonstrated the long-term safety and tolerability of Lonhala Magnair in comparison with tiotropium bromide delivered by the HandiHaler device in adults with moderate to very severe COPD. Overall, treatment-emergent adverse events were similar for patients receiving glycopyrrolate and those receiving tiotropium during a 48-week period, the company said.

Sunovion expects to be available in US pharmacies in early 2018.

Lonhala Magnair should not be started in patients with acutely deteriorating COPD or to relieve sudden symptoms of COPD and should not be used more than twice daily. It is contraindicated in patients with hypersensitivity to glycopyrrolate or any of the ingredients.

AstraZeneca today announced that the US Food and Drug Administration (FDA) has approved Bydureon® BCise™ (exenatide extended-release) injectable suspension, a new formulation of Bydureon (exenatide extended-release) injectable suspension in an improved once-weekly, single-dose autoinjector device for adults with type-2 diabetes whose blood sugar remains uncontrolled on one or more oral medicines in addition to diet and exercise, to improve glycemic control.

Unlike other glucagon-like peptide-1 (GLP-1) receptor agonists, Bydureon BCise has a unique, continuous-release microsphere delivery system designed to provide consistent therapeutic levels of the active ingredient, exenatide, to help patients reach and maintain steady state. The new formulation in the innovative Bydureon BCise device is proven to reduce blood sugar levels, with the added benefit of weight loss, although not a weight loss medicine.

Across two clinical trials, average HbA1c reductions of up to 1.4% and average weight loss of up to 3.1 pounds were achieved when used as monotherapy or as an add-on to metformin, a sulfonylurea, a thiazolidinedione, or any combination of two of these oral anti-diabetic medicines at 28 weeks. The most common adverse reactions reported in ≥5% of patients in clinical trials were nausea (8.2%) and adverse events associated with injection-site nodules (10.5%).

Bydureon BCise is designed for ease and patient convenience in a once-weekly, pre-filled device with a pre-attached hidden needle. The medication is administered in three simple steps – mix, unlock, inject.

Ruud Dobber, President, AstraZeneca US and Executive Vice President, North America, said: “We know that physicians have established longstanding confidence in the significant HbA1c reduction Bydureon provides their patients to help achieve consistent control, with the added benefit of weight loss. With the approval of Bydureon BCise, we’re now introducing a new formulation in an improved, easy-to-use device, that will help enhance the patient experience.”

Bydureon BCise will be available for patients in the US in the first quarter of 2018. Bydureon Pen will also remain available for patients. A regulatory application for the new autoinjector device has also been accepted by the European Medicines Agency.

The US Food and Drug Administration (FDA) last week approved an antibiotic called secnidazole (Solosec, Symbiomix Therapeutics) for women with bacterial vaginosis.

Secnidazole is the first single-dose oral treatment for bacterial vaginosis, the most common vaginal infection in women aged 15 to 44 years, according to the Centers for Disease Control and Prevention.

A dose of secnidazole comes in the form of a 2-g packet of granules. Patients sprinkle the granules on applesauce, yogurt, or pudding and eat the mixture within 30 minutes without chewing or crunching the granules.

Most current antibiotics for bacterial vaginosis must be taken for 5 to 7 days, and often more than once a day. As a single-dose treatment, secnidazole promises to improve adherence and the likelihood of a cure, Symbiomix Therapeutics stated in a news release.

The FDA determined that secnidazole was safe and effective on the basis of two randomized, placebo-controlled clinical trials involving 333 nonpregnant women up to age 54 years.

Vulvovaginal candidiasis, headache, nausea, dysgeusia, vomiting, and diarrhea were among the most common adverse events observed in the two studies. The drug’s label warns that vulvovaginal candidiasis associated with the use of secnidazole may require treatment with an antifungal drug.

The agency also warns about the potential risk for carcinogenicity because mice and rats treated chronically with drugs structurally related to secnidazole have developed tumors.

“Avoid chronic use.”

The drug is not recommended for women who are breast-feeding. If they take it, however, they should discontinue breast-feeding for 96 hours afterward.

The FDA approved Kymriah (tisagenlecleucel) for certain pediatric and young adult patients with a form of acute lymphoblastic leukemia (ALL) that is refractory or has relapsed at least twice.

Novartis announced today that the US Food and Drug Administration (FDA) has approved Kymriah^(TM)(tisagenlecleucel) suspension for intravenous infusion, formerly CTL019, the first chimeric antigen receptor T cell (CAR-T) therapy, for the treatment of patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse. Kymriah is a novel immunocellular therapy and a one-time treatment that uses a patient’s own T cells to fight cancer. Kymriah is the first therapy based on gene transfer approved by the FDA.

Kymriah is an innovative immunocellular therapy that is a one-time treatment. Kymriah uses the 4-1BB costimulatory domain in its chimeric antigen receptor to enhance cellular expansion and persistence. In 2012, Novartis and the University of Pennsylvania (Penn) entered into a global collaboration to further research, develop and commercialize CAR-T cell therapies, including Kymriah, for the investigational treatment of cancers.

 

Kymriah(TM) (tisagenlecleucel) Important Safety information

Kymriah may cause side effects that are fatal or life-threatening, such as Cytokine Release Syndrome (CRS) or Neurological Toxicities. Patients with CRS may experience symptoms including high fever, difficulty breathing, chills/shaking chills, severe nausea, vomiting and diarrhea, severe muscle or joint pain, very low blood pressure or dizziness/lightheadedness. Patients may be admitted to the hospital for CRS and treated with other medications.

Patients with neurological toxicities may experience symptoms such as altered or decreased consciousness, headaches, delirium, confusion, agitation, anxiety, seizures, difficulty speaking and understanding, or loss of balance. Patients should be advised to call their health care provider or get emergency help right away if they experience any of these signs and symptoms of CRS or neurological toxicities.

Because of the risk of CRS and neurological toxicities, Kymriah is only available through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called Kymriah REMS.

Serious allergic reactions, including anaphylaxis, may occur after Kymriah infusion. Kymriah can increase the risk of life-threatening infections that may lead to death. Patients should be advised to tell their health care provider right away if they develop fever, chills, or any signs or symptoms of an infection.

Patients may experience prolonged low blood cell counts (cytopenia), where one or more types of blood cells (red blood cells, white blood cells, or platelets) are decreased. The patient’s health care provider will do blood tests to check all of their blood cell counts after treatment with Kymriah. Patients should be advised to tell their health care provider right away if they get a fever, are feeling tired, or have bruising or bleeding.

Patients may experience hypogammaglobulinemia, a condition in which the level of immunoglobulins (antibodies) in the blood is low and the risk of infection is increased. It is expected that patients may develop hypogammaglobulinemia with Kymriah, and may need to receive immunoglobulin replacement for an indefinite amount of time following treatment with Kymriah. Patients should tell their health care provider about their treatment with Kymriah before receiving a live virus vaccine.

After treatment with Kymriah, patients will be monitored life-long by their health care provider, as they may develop secondary cancers or recurrence of their leukemia.

Patients should not drive, operate heavy machinery, or do other dangerous activities for 8 weeks after receiving Kymriah because the treatment can cause temporary memory and coordination problems, including sleepiness, confusion, weakness, dizziness and seizures.

Some of the most common side effects of Kymriah included: difficulty breathing, fever (100.4°F/38°C or higher), chills/shaking chills, confusion, severe nausea, vomiting and diarrhea, severe muscle or joint pain, very low blood pressure, and dizziness/lightheadedness. However, these are not all of the possible side effects of Kymriah. Patients should talk to their health care provider for medical advice about side effects.

Prior to a female patient starting treatment with Kymriah, their health care provider may do a pregnancy test. There is no information available for Kymriah use in pregnant or breast-feeding women. Therefore, Kymriah is not recommended for women who are pregnant or breast feeding. If either sex partner has received Kymriah, patients should talk to their health care provider about birth control and pregnancy.

Patients should tell their health care provider about all the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

After receiving Kymriah, patients should be advised that some commercial HIV tests may cause a false positive test result. Patients should also be advised not to donate blood, organs, or tissues and cells for transplantation after receiving Kymriah.

Duzallo was approved by the U.S. Food and Drug Administration (FDA) as a once-daily oral treatment for hyperuricemia associated with gout in patients who have not achieved target serum uric acid (sUA) levels with a medically appropriate daily dose of allopurinol alone. Duzallo is not recommended for the treatment of asymptomatic hyperuricemia. Ironwood expects Duzallo to be commercially available early in the fourth quarter of 2017.

Duzallo is the first drug that combines the current standard of care for the treatment of hyperuricemia associated with gout, allopurinol, with the most recent FDA-approved treatment for this condition, lesinurad. This fixed-dose combination provides a dual mechanism of action in a single tablet that can address both underlying causes of hyperuricemia – overproduction and underexcretion of serum uric acid.

Gout is a highly symptomatic and painful form of inflammatory arthritis caused by hyperuricemia, or elevated sUA levels in the blood, which can lead to painful flares and serious potential long-term health consequences.

“The approval of Duzallo provides a new fixed-dose and dual-mechanism treatment option to help patients with uncontrolled gout achieve target serum uric acid levels. This represents an important and needed new option in the treatment of hyperuricemia,” said Michael A. Becker, M.D., professor emeritus of medicine, Department of Medicine, The University of Chicago, Chicago, IL. “Gout is a serious and potentially progressive and debilitating inflammatory disease. Getting patients with gout to serum urate goal, and keeping them at or below goal, are essential to success in treating these patients. Duzallo will help reduce the significant unmet need among patients in the U.S. who fail to get their serum uric acid levels to goal despite taking allopurinol alone.”

“With Duzallo, nearly twice as many patients with uncontrolled gout may be able to achieve target serum uric acid levels compared to those patients taking allopurinol alone, which is important, considering the significant unmet need among uncontrolled gout patients to get to goal of under 6 mg/dL,” said Tom McCourt, senior vice president of marketing and sales and chief commercial officer at Ironwood.

Duzallo (lesinurad and allopurinol) is a once-daily oral therapy that contains lesinurad 200 mg plus allopurinol 300 mg; it is also available in a lesinurad 200 mg plus allopurinol 200 mg dosage. Duzallo is approved by the FDA as a once-daily oral treatment for hyperuricemia associated with gout in patients who have not achieved target serum uric acid (sUA) levels with a medically appropriate daily dose of allopurinol alone. Duzallo is not recommended for the treatment of asymptomatic hyperuricemia. Allopurinol is an XOI whose action differs from that of uricosuric agents such as lesinurad. Allopurinol reduces the production of uric acid (UA); lesinurad increases renal excretion of UA by selectively inhibiting the action of URAT1, the UA transporter responsible for the majority of renal UA reabsorption. The dual-mechanism combination of Duzallo can address both inefficient excretion and overproduction of UA, thereby lowering sUA levels. Duzallo should be taken in the morning with food and water, and patients should be advised to stay well hydrated when taking Duzallo (about 2 liters of liquid a day).

Melinta Therapeutics, announced today that the U.S. Food and Drug Administration (FDA) has approved Baxdela (delafloxacin), indicated in adults for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible bacteria. Baxdela is a fluoroquinolone that exhibits activity against both gram-positive and gram-negative pathogens, including MRSA (methicillin-resistant Staphylococcus aureus), and is available in both intravenous (IV) and oral formulations.

“Antibiotic resistance is a growing concern, and physicians need more tools in the fight against this threat to modern medicine. Approval of new therapies like Baxdela, which is effective against MRSA and other serious pathogens, provides physicians another option in addressing the challenges of ABSSSI patients,” said Dr. David Hooper, professor of medicine, Harvard University, and chief of Infection Control, associate chief, Division of Infectious Diseases, Massachusetts General Hospital.

Baxdela is indicated in adults for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible isolates of the following:

• Gram-positive organisms: Staphylococcus aureus (including methicillin-resistant [MRSA] and methicillin-susceptible [MSSA] isolates), Staphylococcus haemolyticus, Staphylococcus lugdunensis, Streptococcus agalactiae, Streptococcus anginosus group (including Streptococcus anginosus, Streptococcus intermedius, and Streptococcus constellatus), Streptococcus pyogenes, and Enterococcus faecalis;
• Gram-negative organisms: Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae, and Pseudomonas aeruginosa.

IMPORTANT SAFETY INFORMATION

WARNING: SERIOUS ADVERSE REACTIONS INCLUDING TENDINITIS, TENDON RUPTURE, PERIPHERAL NEUROPATHY, CENTRAL NERVOUS SYSTEM EFFECTS, AND EXACERBATION OF MYASTHENIA GRAVIS

Fluoroquinolones have been associated with disabling and potentially irreversible serious adverse reactions that have occurred together, including:

• Tendinitis and tendon rupture
• Peripheral neuropathy
• Central nervous system effects

 

 

In the long-standing debate over whether antidepressants are safe to take during pregnancy, a new study suggests that exposure to the drugs in the womb might bump up a child’s risk of autism.

The risk of autism was 45 percent higher for kids whose moms took antidepressants compared to kids born to mothers with psychiatric disorders who weren’t prescribed antidepressants, the study found.

“We found consistent results pointing towards a small effect of antidepressants with autism, especially higher functioning forms of autism without intellectual disability,” said lead researcher Dheeraj Rai. He is a senior lecturer in psychiatry with the University of Bristol in the United Kingdom.

“We think it is important to keep in mind the absolute risk, which is small,” Rai said. “Over 95 percent of women in the study who took antidepressants during pregnancy did not have a child with autism.”

Also, the study wasn’t designed to prove a cause-and-effect relationship, and only found an association between antidepressants and the risk of autism.

What’s more, further analysis by the researchers indicated that forgoing antidepressants during pregnancy would not cause a drastic reduction in overall autism rates, noted Thomas Frazier, chief science officer for Autism Speaks, a nonprofit autism advocacy organization.

“It turns out you would prevent 2 percent of autism cases” if no pregnant women ever took antidepressants, Frazier said.

“It’s definitely not a major contributor,” Frazier added. “It appears to be a significant and real relationship, but it’s not a strong one in terms of how many cases of autism this would prevent.”

Another recent study, published online July 12 in JAMA Psychiatry, had better news for depressed moms-to-be. That research found no statistically significant difference in intellectual disability in children born to mothers taking antidepressants compared to kids whose moms didn’t take the drugs.

For the current study, Rai and his research team analyzed data from more than 254,000 children aged 4 to 17 living in Stockholm between 2001 and 2011.

Almost 5,400 of the children were diagnosed with autism. More than 3,300 of the children were exposed to antidepressants during pregnancy. And more than 12,000 children were born to mothers with psychiatric disorders who weren’t taking an antidepressant in pregnancy, the study revealed.

About 4 percent of children exposed to antidepressants had been diagnosed with autism. Meanwhile 2.9 percent of children born to a woman with a history of psychiatric problems who didn’t take antidepressants during pregnancy developed autism.

Antidepressants were more strongly associated with cases of autism that didn’t include intellectual disability, the researchers said.

No one is certain why antidepressants might be linked to autism, but most antidepressants act by increasing brain levels of a neurotransmitter called serotonin, Rai and Frazier said.

“Serotonin is important in brain development and higher levels have been observed in children with autism,” Rai said. He added that animal research has shown that exposing animal fetuses to antidepressants that boost serotonin levels causes autism-like symptoms in the animals.

At the same time, Rai said it is too early to rule out the possibility that depression itself increases the risk of autism, rather than the medications prescribed to treat depression.

“It is known that chronic forms of stress could affect brain development of the fetus,” Rai said. “There is also the possibility of a common genetic pathway — for example, women who have a higher genetic risk of autism could also be more likely to have severe depression and be prescribed antidepressants.”

Rai and Frazier also agreed that pregnant women with depression should not stop taking their medicine without first talking it over with their doctor.

“They should not base decisions about the use of antidepressants during pregnancy on any one study, especially when the research evidence is conflicting, as in this case where different studies have reached different conclusions,” Rai said.

“There could be severe risks of stopping or not taking antidepressants during pregnancy both to the mother and the fetus, so the benefits of these medications for mothers who need them should not be forgotten,” he said.

Rai concluded that this study should be seen as a “small effort contributing to the understanding of the complex mechanisms behind autism,” rather than evidence that antidepressants can in and of themselves cause autism.

The study was published online July 19 in the BMJ.

At least three people worldwide are infected with totally untreatable strains of gonorrhea which they are likely to be spreading to others through sex, the World Health Organization (WHO) said on Friday.

Giving details of studies showing a “very serious situation” with regard to highly drug–resistant forms of the sexually–transmitted disease (STD), WHO experts said it was “only a matter of time” before last–resort gonorrhea antibiotics would be of no use.

“Gonorrhea is a very smart bug,” said Teodora Wi, a human reproduction specialist at the Geneva–based UN health agency.

“Every time you introduce a new type of antibiotic to treat it, this bug develops resistance to it.”

The WHO estimates 78 million people a year get gonorrhea, an STD that can infect the genitals, rectum and throat.

The infection, which in many cases has no symptoms on its own, can lead to pelvic inflammatory disease, ectopic pregnancy and infertility, as well as increasing the risk of getting HIV.

Wi, who gave details in a telephone briefing of two studies on gonorrhea scheduled for publication in the journal PLOS Medicine, said one had documented three specific cases – one each in Japan, France and Spain – of patients with strains of gonorrhea against which no known antibiotic is effective. “These are cases that can infect others. It can be transmitted,” she told reporters. “And these cases may just be the tip of the iceberg, since systems to diagnose and report untreatable infections are lacking in lower–income countries where gonorrhea is actually more common.”

DRUG RESISTANCE

The WHO’s program for monitoring trends in drug–resistant gonorrhea found in a study that from 2009 to 2014 there was widespread resistance to the first–line medicine ciprofloxacin, increasing resistance to azithromycin, and the emergence of resistance to last–resort treatments––extended–spectrum cephalosporins (ESCs).

In most countries, it said, ESCs are now the only single antibiotics that remain effective for treating gonorrhea. Yet resistance to them has already been reported in 50 countries.

Manica Balasegaram, director of the Global Antibiotic Research and Development Partnership, said the situation was “grim” and there was a “pressing need” for new medicines.

The pipeline, however, is very thin, with only three potential new gonorrhea drugs in development and no guarantee any will prove effective in final–stage trials, he said.

“We urgently need to seize the opportunities we have with existing drugs and candidates in the pipeline,” he told reporters. “Any new treatment developed should be accessible to everyone who needs it, while ensuring it is used appropriately, so that drug resistance is slowed as much as possible.”