A-315675 is a novel, pyrrolidine-based compound that was evaluated in this study for its ability to inhibit A and B strain influenza virus neuraminidases in enzyme assays and influenza virus replication in cell culture. A-315675 effectively inhibited influenza A N1, N2, and N9 and B strain neuraminidases with inhibitor constant (Ki) values between 0.024 and 0.31 nM. These values were comparable to or lower than the Ki values measured for oseltamivir carboxylate (GS4071), zanamivir, and BCX-1812, except for the N1 enzymes that were found to be the most sensitive to BCX-1812. The time-dependent inhibition of neuraminidase catalytic activity observed with A-315675 is likely due to its very low rate of dissociation from the active site of neuraminidase. The half times for dissociation of A-315675 from B/Memphis/3/89 and A/Tokyo/3/67 (H3N2) influenza virus neuraminidases of 10 to 12 h are significantly slower than the half times measured for oseltamivir carboxylate (33 to 60 min). A-315675 inhibited the replication of several laboratory strains of influenza virus in cell culture with potencies that were comparable or superior to those for oseltamivir carboxylate and BCX-1812, except for the A/H1N1 viruses that were found to be two- to fourfold more susceptible to BCX-1812. A-315675 and oseltamivir carboxylate exhibited comparable potencies against a panel of A/H1N1 and A/H3N2 influenza virus clinical isolates, but A-315675 was found to be significantly more potent than oseltamivir carboxylate against the B strain isolates. The favorable in vitro results relative to other clinically effective agents provide strong support for the further investigation of A-315675 as a potential therapy for influenza virus infections.
KBTX College Station Texas -
The CDC has already offered assistance on this cluster of cases. The illnesses started with flu-like symptoms, then progressed to pneumonia and, in some cases, organ failure. All of the patients initially tested negative for the flu.
News about the illness has people packing into doctors offices and clinics.
At the Conroe Urgent Care Clinic Thursday, at least 18 patients came in with flu-like symptoms.
“We’re testing at least five to seven people positive for H1N1 [daily] as opposed to October when we hardly had any," said Physician Assistant Derrick Goodwill.
The commonly used RAPID flu test is not very reliable.
“The recommendation right now is to give Tamiflu to patients even if they don’t test positive,” Goodwill said.
COMMENT An EUA might be in order if this gets much worse. Do we need 6-10 months of delay while people get seriously ill from something which was previously the subject of an EUA and is approved in at least 3 other countries.
They have said 2 things 1) file by year end 2) have ready for 2014-15 flu season. Given the NDA timeline of about 10 months(unless "accelerated review"), that means within the next 10 days to file-on last conf call, said one of their people wasn't there because he was working on the filing-so 5 catalysts in this timeline-File, Accept submission after 60 day prelim review, 74 day letter, Advisory Committee, Approval -overall 6-10months (and of course, Stockpile)
Once the application is submitted, the FDA has 60 days to conduct a preliminary review which will assess whether the NDA is "sufficiently complete to permit a substantive review". If the NDA is found to be insufficiently complete (and reasons for this can vary from a simple administrative mistake in the application to a requirement to reconduct much of the testing), then the FDA rejects the application with the issue of a Refuse to File letter which is sent to the applicant explaining where the application has failed to meet requirements.
Assuming that everything is found to be acceptable, the FDA will decide if the NDA will get a standard or accelerated review and communicate the acceptance of the application and their review choice in another communication known as the 74-day letter. A standard review implies an FDA decision within about 10 months while a priority review should complete within 6 months
Half of their editorial note for the Dec 20 update is about antivirals - just get that NDA filed and they will move it.
Treatment with antivirals is recommended as soon as possible for patients with confirmed or suspected influenza who have severe, complicated, or progressive illness; who require hospitalization; or who are at higher risk for influenza complications,††† without waiting for confirmatory testing (3). Antiviral treatment also may be considered for outpatients with confirmed or suspected influenza who do not have known risk factors for severe illness, and is most effective when treatment is initiated within 48 hours of illness onset. Recommended antiviral medications include oseltamivir (Tamiflu) and zanamivir (Relenza). The majority of influenza viruses tested for the 2013–14 season since October 1, 2013, have been susceptible to oseltamivir. The seven oseltamivir-resistant pH1N1 viruses identified in late October through November were from three different states in the South and West. Sporadic oseltamivir-resistant pH1N1 virus infections, including small geographic clusters, have occurred previously, but the public health impact has been limited (4,5). This situation is being closely monitored. All influenza viruses, including those from the oseltamivir-resistant cluster, tested since October 1, 2013, have been susceptible to zanamivir.
In editorial comments on flu update
Antiviral medications continue to be an important adjunct to vaccination for reducing the health impact of influenza..
Somebody else was having trouble posting, so I'll try
Wells Fargo maintained an Outperform rating on BioCryst Pharma . Comments follow news BioCryst has selected two optimized plasma kallikrein inhibitors to advance into preclinical development as potential once-daily, oral treatments for the prevention of hereditary angioedema (HAE) attacks.
Analyst Brian Abrahams said, "While the second generation compounds are still at an early preclinical stage, PK profiles of the compounds look promising, suggesting that they could potentially further improve upon '4161's profile (and IP) and help the longterm life cycle management of the company's potential HAE franchise. We continue to believe '4161's proofofconcept study (OPuS1), expected to read out by mid2014, has a good probability of success, and that BCRX shares undervalue the potential HAE opportunity on a risk/reward basis."
twice in December newsletter (see HAEi site, news tab, newsletter), along with Shire and others, but points out clinical trials Opus 1 and follow on drug candidates. They would probably like some good news by their global meeting in May 2014.
ISID Promed mail reports a death - elderly lady, but the problem is, these "wet" ie publicly slaughtered fowl are all over China.
This report describes a novel case of avian influenza (H10N8) virus infection, contracted in Jiangxi province of mainland China, by an immunocompromised elderly lady. Similarly to other avian influenza virus infections encountered so far (with the exception of H5N1 virus) there has been no onward transmission of infection to other related or unrelated humans. Circumstantial evidence suggests that the infection was contracted by exposure to domestic fowl in a local "wet" market. The patient died.
ISID promed reports, antivirals are all we've got.
In another lab development, researchers based at Icahn School of Medicine at Mount Sinai in New York City today [10 Dec 2013] reported findings from experiments that suggest oseltamivir-resistant strains of H7N9 transmit and cause disease just as effectively as strains that aren't resistant to the drug. The team published its findings in the latest online edition of Nature Communications.
Analysis of a strain from one of Shanghai's 1st H7N9 patients revealed the resistance marker in one of the strains, and resistant H7N9 strains have also been linked to clinical treatment failures in some of China's severely ill patients. The reports raised concerns, because, so far, there is no vaccine against the novel strain, which leaves antiviral medications as a key treatment and prevention measure.
H7N9 found in 3 samples from poultry markets, but nobody told the chicken sellers
Samples from 2 Shenzhen wet markets have tested positive for the H7N9 bird flu virus that has infected 2 people in Hong Kong.
Confirmation of the test findings came 2 days after the municipal government said the border city could not be confirmed as the source of the outbreak.
The Health and Family Planning Commission of Guangdong said yesterday [Tue 10 Dec 2013] that H7N9 had been detected in 3 samples of blood and urine taken from poultry stalls at 2 wet markets in Shenzhen's Longgang district.
The infected samples were among 70 collected on Tue [10 Dec 2013] from 13 wet markets across the city. One infected sample came from a chopping board at a stall selling live poultry at the Henggang market. The other 2 were found in chicken urine from a stall at the Kangqiao market in the Nanwan neighbourhood.
The commission said the risk of bird flu spreading in the province was high and warned the public to stay alert.
But last night [10 Dec 2013], traders at the Kangqiao market said sales were continuing. "They came to collect samples, but we heard nothing about the test results, and trade continued all day long today," one trader said.
University of Hong Kong microbiologist Ho Pak-leung said he believed the deadly virus was already spreading in Guangdong and the surrounding areas.
If my child can’t swallow capsules, how do I open Tamiflu® capsules and mix the medicine?
Pour a small amount (about a spoonful) of the thick, sweetened liquid into a cup or bowl. Carefully open the Tamiflu® capsule prescribed by your doctor and pour out all of the powder inside the capsule and mix it into the liquid. The exact amount of liquid used doesn’t matter, as long as the powder inside the capsule is mixed in well. All of the medicine may not dissolve, just be sure it is all well mixed. Use only the prescribed dose.
All publicly traded companies have to comply with regulation FD, which requires release of material information, ie that which would make an investor buy or sell stock, on an open and widely disseminated basis. I am not sure an investment conference statement, without a simultaneous press release,of significant material information would comply with FD. On the other hand, the HAEA, or HAEi organizations are not so limited, except by any confidentiality agreements doctors or patients signed. This trial is taking place in Germany where they have electronic diaries of HAE onset.
That Ms Swisher writes an article about gender equality in tech and twitter's board, but can't bring herself to mention Yahoo's leadership as a step forward, says a lot about the thin veneer of balance over a big layer of bias in her "reporting"
In a paper released Thursday [28 Nov 2013] in the journal BMC Medicine, Vespignani and his collaborators provide those hard numbers, and they aren't terribly reassuring.
"This study provides a very accurate modeling approach to assess the probability of containment in the case of accidental escape," explained Vespignani, who holds joint appointments in the College of Science, College of Computer and Information Science, and Bouve College of Health Sciences. "Unfortunately, there are large chances that the outbreak will not be contained."
Vespignani and his research team used census data from the city of Rotterdam in the Netherlands to create a computational model that tracked how an experimental virus would spread if it were accidentally released from a facility operating at a biosafety level of 3 or 4. These labs carry out the most health-hazardous biological research in the world and are often located in populous urban areas.
(And what's your contingency plan - a big antiviral stockpile. )
In children rendered critically ill by the flu, treatment with NAIs reduced their risk of dying by 64 percent, the study found.
Researchers found that in recent years, however, fewer than two-thirds of severely ill children received NAIs while hospitalized for the flu.
Dr. Octavio Ramilo, a professor of pediatrics at Ohio State University, said a flu-stricken child who is sick enough to go to the hospital needs to receive antiviral therapies immediately.
"The minute you come to the hospital, we [should] start you on antiviral therapy," said Ramilo, who also is chief of infectious diseases at Nationwide Children's Hospital in Columbus, Ohio.
China's armed forces will adopt defensive emergency measures to respond to aircraft that do not cooperate in the identification or refuse to follow the instructions, it said.
So long as nothing breaks out over South China Sea - hearing today
The United States is gravely concerned about China's new long-range nuclear bombers that can target previously unreachable US military bases in the Pacific, according to a new report.
The US-China Economic and Security Review Commission warns in its annual report that China is 'rapidly expanding and diversifying' its ability to strike US bases, ships and aircraft throughout the Pacific, even places like Guam that were previously out of reach, The Foreign Policy magazine reported on Wednesday.
The House Armed Services Committee is set to discuss China's Hongzha-6K bomber at a hearing on Wednesday when members of the commission will testify about their report.