First Human Zika Vaccine Trial

August 20, 2018

Researchers are launching the first human trial of an experimental live Zika vaccine. The vaccine, which contains a weakened version of the virus, was de­veloped by scientists at the National Institute of Allergy and Infectious Diseases (NIAID). The trial plans to enroll a total of 28 healthy, non-pregnant adults, ages 18 to 50, at Johns Hopkins School of Public Health Center for Immunization Research and at the Vaccine Testing Center at Larner College of Medicine at the University of Vermont. Trial participants will be randomly assigned to receive a single subcutaneous dose of the experimental vaccine (20 participants) or a placebo (eight participants). Neither they nor investigators will know who is receiving the real thing. Participants will keep track of their tem­perature on diary cards at home – and return to the clinic for periodic checkups for about six months. Researchers will take blood samples during visits to see if they’re developing antibodies in response to the vaccine. Anna Durbin, a professor of International health at Hopkins School of Public Health, is leading the Phase I clinical trial. Most people infected with the Zika virus — primarily transmitted by certain mosquitoes — have mild to no symptoms. But it can cause serious birth defects and developmental problems in babies born to women infected during pregnancy. That’s why the Centers for Disease Control and Prevention advises women who are pregnant or planning to become pregnant not to travel to areas with a known Zika risk. “Zika virus infection remains a significant threat to pregnant women and their developing fetuses, and we can expect to see periodic outbreaks and cases in areas where Aedes aegypti mosquitoes thrive,” said NIAID Director Anthony Fauci. “NIAID remains committed to developing safe and effective Zika vaccines, and we are pleased to begin clinical testing of a live attenuated candidate.”

“Triple Pill” May Keep a Lid on BP
A low-dose, three-in-one pill may be an easy new way to treat high blood pressure. A trial led by The George Institute for Global Health in Sidney, Australia, found that a whopping 70 percent of patients who took the so-called Triple Pill — containing half doses of three different meds — reached blood pressure targets, compared to just over half of those who received usual care. Typically, patients begin treatment with one drug at a very low dose that’s gradually increased with other drugs added to the mix to reach target blood pressure measures. It takes time and tinkering with meds and doses to come up with the most effective cocktail. That means patients have to frequently visit their doctor to see if the meds are working or if they need to be changed or doses adjusted to meet treatment goals. “This is not only time inefficient, it’s costly. We also know that many doctors and patients find it too complicated and often don’t stick to the process,” said study co-author Ruth Webster. In an attempt to find a simpler approach, researchers enrolled 700 patients with an average age of 56 and blood pressure of 154/90 mm Hg in a six-month trial. Participants were randomly assigned either the combo pill or standard care. The test tablet contained the blood pressure meds telmisartan (20 mg), amlodipine (2.5 mg), and chlorthalidone (12.5 mg). The findings, published in JAMA: a significantly higher proportion of patients receiving the “Triple Pill” hit their target blood pressure of 140/90 or less (with lower targets of 130/80 for patients with diabetes or chronic kidney disease). The three-in-one option was not only more effective, it was also found to be safe, researchers said. The George Institute says it plans to examine the cost-effectiveness of the “Triple Pill” — and test its appeal among doctors and patients. An estimated one in three U.S. adults — around 75 million people — suffer from high blood pressure. But only about 54 percent have it under control, according to the Centers for Disease Control and Prevention (CDC). The condition ups the risk for heart attack and stroke, two of the leading causes of death in the U.S.

FDA OKs Optivo for Lung Cancer
The FDA last week approved Bristol-Myers Squibb’s Opdivo (nivolumab) for patients with metastatic small cell lung cancer (SCLC) that fails to respond to platinum-based chemotherapy and at least one other therapy. “Small cell lung cancer can be a very challenging disease, particularly for those who have already been through multiple types of treatment, as most patients relapse within a year of diagnosis,” said Andrea Ferris, president and chairman of the LUNGevity Foundation. “This approval marks a major milestone for the patients touched by this unrelenting disease and may motivate them to pursue further treatment where there previously were no other approved options.” The agency OK’d Optivo after 12 percent of 109 patients (in the SCLC cohort of the ongoing Phase I/II CheckMate -032 clinical trial) responded to it after chemo and another therapy failed. According to researchers, 12 patients had a partial and one (0.9 percent) a complete response. The median duration of response (DOR) was 17.9 months. The drug was discontinued in 10 percent of patients and one dose was withheld in 25 percent because of side effects. Some 45 percent of trial participants experienced serious side effects. SCLC is a very aggressive cancer that makes up about 10 to 15 percent of all lung cancers. About 27,000 cases are diagnosed in the U.S. each year.

Schizophrenia: If At First You Don’t Succeed, Try Clozapine?
A new study suggests doctors may want to consider prescribing the potent, atypical an­tipsychotic drug clozapine earlier for schizophrenia if a typical antipsychotic doesn’t work. Physi­cians generally don’t prescribe clozapine for newly diagnosed patients until they’ve tried at least two other less potent antipsychotics. But a trial found that if the first drug didn’t help, switching to another similar antipsychotic usually didn’t have much of a clinical impact, either. So researchers concluded it might be more effective to skip the second antipsychotic – and move onto clozapine earlier. New York’s Mount Sinai Hospital recruited 486 newly diagnosed schizophrenia patients and gave them up to 800 mg per day of the antipsy­chotic amisulpride for four weeks. Patients whose symptoms didn’t subside were then either continued on amisulpride or switched to up to 20 mg per day of olanzapine, another typical antipsychotic, for six more weeks. After 10 weeks, patients still suffering from hallucinations and/or other schizophrenia symptoms were given up to 900 mg per day of clozapine for 12 weeks. Ten weeks is gener­ally considered very early to start prescribing clozapine. But lead researcher Rene Kahn says the trial found that trying it then “could potentially save time and reduce suffering.” The findings were published The Lancet Psychiatry.

Cetuximab Can’t Clear Trial for Throat and Mouth Cancer
Cetuximab, a targeted anti-cancer drug believed to be less toxic than its rival cisplatin, has failed to show it can help curb the growth of throat and mouth cancers caused by HPV. There was a lot of hope for cetuximab when researchers began a Phase III trial of 849 patients with HPV-related mouth or throat cancers in June 2011 in which they received a combination of radiation therapy and either cetuximab or the more potent cisplatin. But researchers found that cetuximab was far less effective than cisplatin at controlling tumor growth. “The goal of this trial was to find an alternative to cisplatin that would be as effective at controlling the cancer but with fewer side effects. We were surprised by the loss of tumor control with cetuximab,” said lead investigator Andy Trotti of the Moffit Cancer Center in Tampa, Florida. Cetuximab, most commonly known by its brand name Erbitux, is already approved for treatment of metastatic colorectal cancer, some cancers of the head and neck, non-small cell lung cancer and a form of skin cancer. Its most common side effects are relatively mild — ranging from a rash to nausea. Cisplatin, on the other hand, may cause kidney damage, hearing loss and bone marrow suppression. Researchers plan to release their full findings in October.

FDA Approves First EpiPen Generic
The FDA last week approved the first direct generic competitor to the EpiPen, paving the way for cheaper competition that may lower prices. The new generic will be made by Israeli generic manufacturer Teva Pharmaceuticals. It was greenlighted after the FDA issued new guidance for generic copies of products like the EpiPen, the most widely prescribed epinephrine auto-injector in the U.S. Epinephrine reduces swelling in airways and increases blood flow in people suffering anaphylaxis or life-threatening reactions to foods, insect stings or medicines. “This approval means patients living with severe allergies who require constant access to lifesaving epinephrine should have a lower-cost option, as well as another approved product to help protect against potential drug shortages,” FDA Commissioner Scott Gottlieb said in a statement. Mylan, which bought the rights to the EpiPen from Pfizer, has been under fire for hiking the price of the EpiPen to more than $600 for a twin pack. The approval covers generic copies of EpiPen and EpiPen Jr. for kids. Teva Pharmaceuticals can market its generic epinephrine auto-injector in 0.3-milligram and 0.15-milligram doses, the FDA said. The company didn’t say how much it would charge for the generic version or when it would be available. Anaphylaxis occurs in approximately one in 50 Americans, according to the FDA. “People who have had an anaphylaxis episode always face the risk of another one,” Gottlieb said. “Because of this risk, they must carry an emergency dose of epinephrine at all times. Many must keep more than one dose at hand.”