Search This Blog

Monday, November 11, 2019

Reata’s bardoxolone successful in late-stage kidney disease study

Reata Pharmaceuticals (NASDAQ:RETAannounces positive results from the Phase 3 part of its Phase 2/3 clinical trial, CARDINAL, evaluating bardoxolone methyl in patients with chronic kidney disease (CKD) caused by a rare inherited disorder called Alport syndrome.
The study met the primary endpoint of statistically valid increase from baseline to week 48 in a measure of kidney function called eGFR (estimated glomerular filtration rate) compared to placebo. Key secondary endpoints were also met.
No safety signals were observed versus the Phase 2 portion.
According to the company, the FDA indicated that a demonstrated improvement in eGFR after one year of treatment may be sufficient to support accelerated approval.
The company will host a conference call tomorrow, November 12, at 8:00 am ET to discuss the data and Q3 results.

FibroGen EPS misses by $0.03, beats on revenue

FibroGen (NASDAQ:FGEN): Q3 GAAP EPS of -$0.57 misses by $0.03.
Revenue of $33.17M (+14.3% Y/Y) beats by $1.56M.
Shares +0.17%.

Injectable, flexible electrode could replace rigid nerve-stimulating implants

IMAGE
By electrically stimulating nerves, neuromodulation therapies can reduce epileptic seizures, soothe chronic pain, and treat depression and a host of other health conditions without the use of conventional drugs like opioids.
Now, University of Wisconsin-Madison biomedical engineers and their collaborators have made a significant advance that could dramatically reduce the cost of neuromodulation therapy, increase its reliability and make it much less invasive.
With a type of electrode that can be injected as a liquid and then cure in the body, the researchers have laid the groundwork for a new kind of neural interface system.
The researchers unveiled their creation, which they’ve dubbed the “injectrode,” in a paper published online this week in the journal Advanced Healthcare Materials.
Today’s neuromodulation treatments rely on surgically implanted devices that can cost up to six figures, require complex procedures to install, and often fail — given that they’re rigid devices attempting to mesh with soft biological tissue.
The researchers’ system leverages an entirely new way of thinking.
“You can inject the liquid around the nerve, and it cures in the body to create a wired contact,” says Kip Ludwig, a UW-Madison professor of biomedical engineering and neurological surgery. “Typical implants are really stiff, and so as the body moves, they wear and tear and break down. Our liquid cures, and the result is much closer to the normal elasticity of tissue. You can actually stretch it and increase its size 150 percent to 200 percent without losing its conductivity.”
To create the injectrode, the researchers mixed a silicone base — similar to surgical glue — with small metal particles to make the liquid sufficiently conductive.
They put their device through a battery of Food and Drug Administration preclinical tests, and used it to induce heart rate changes in pigs by stimulating their vagus nerve, an approach that’s shown promise for treating heart failure, hypertension and other maladies.
“We essentially went through the standard repertoire of electrochemical tests to show this acts like a standard wire electrode that could be used to stimulate the nerve,” says James Trevathan, a postdoctoral fellow in Ludwig’s lab and first author on the study.
Ludwig co-authored the study and cofounded Neuronoff, a company based on the injectrode, with Case Western Reserve University biomedical engineering professor Andrew Shoffstall and Neuronoff CEO Manfred Franke. They’re also part of a multi-institution team that recently secured a $2.1 million grant from the National Institutes of Health to further develop the system to stimulate spinal nerves as a non-opioid alternative to treating chronic back pain.
The paper and grant represent crucial early steps in a larger effort to create a minimally invasive system for neural stimulation.
As part of the NIH grant, the researchers are testing a scheme in which they inject the fluid around the nerve, then extrude a thin insulated string of the material back to just underneath the surface of the skin, where they inject more of the composite material. Then they can use a basic transcutaneous electrical nerve stimulation, or TENS, unit — the kind you can buy at a department store or pharmacy — to stimulate the nerve from the surface of the skin, making the whole setup less expensive and more adaptable compared to traditional implanted electrodes.
“We’re making a bypass from the surface of the skin to the location we want to stimulate,” says Ludwig, who envisions eventually using a robotic surgical system for a procedure that would be akin to getting a tattoo. “As we learn more and more about how to interface with the nervous system, we’re not limited to what we’ve implanted through an invasive surgical procedure. We can actually change how we stimulate, how we talk to the nerve, because we’re essentially just routing our connection to this deep nerve back to the surface of the skin.”
###
Other coauthors on the paper include Professor Justin Williams and senior scientist Aaron Suminski of the UW-Madison Department of Biomedical Engineering, Doug Weber of the University of Pittsburgh, and researchers from Mayo Clinic.
This research was supported by the Defense Advanced Research Projects Agency (grant N66001?17?2?4010), National Science Foundation (DMR?1720415) and NIH (1U18EB029251?01).

Frequent pot smokers face twice the odds for stroke

Smoking pot doesn’t do your heart or your brain any favors, a pair of new studies shows.
Frequent pot smokers are more than twice as likely to suffer a  compared with those who don’t partake, the first study found.
They’re also more likely to be hospitalized for a dangerously erratic  rhythm, according to the second study.
Both studies are to be presented at an upcoming meeting of the American Heart Association (AHA), in Philadelphia, Nov. 16 to 18. Research presented at meetings is typically considered preliminary until published in a peer-reviewed journal.
The findings are “thought provoking at a time when there is a great push to legalize marijuana, and the herb and its metabolites are being promoted as a cure-all for a myriad of medical conditions and ailments,” said Dr. Ranjit Suri, an electrophysiologist at Mount Sinai St. Luke’s in New York City. Suri was not part of either study.
The first study found that non-smokers who use marijuana more than 10 days a month are nearly 2.5 times more likely to have a stroke versus non-users.
For the study, researchers evaluated federal survey data on more than 43,000 adults, aged 18 to 44, of whom about 14% reported using pot in the last 30 days.
The study team was surprised that people so young had such an elevated stroke risk, said lead author Tarang Parekh, a health policy researcher at George Mason University in Fairfax, Va.
“Young cannabis users, especially those who use tobacco and have other  for strokes, such as , should understand that they may be raising their risk of having a stroke at a young age,” he said.
Prior studies have shown that marijuana can increase blood clotting and cause arteries to narrow, both of which can increase the risk of stroke, Parekh said. This might explain the observed association.
In the second study, researchers found that people who compulsively use cannabis have an up to 50% greater risk of being hospitalized for an arrhythmia—an erratic heartbeat that can increase risk of stroke, heart attack or heart failure.
The team compared more than 570,000 people hospitalized with an arrhythmia against more than 67 million patients hospitalized for other reasons, looking specifically at those diagnosed with cannabis-use disorder.
People aged 25 to 34 who compulsively used cannabis were 52% more likely to land in the hospital suffering an arrhythmia, the researchers found, while those aged 15 to 24 were 28% more likely to be hospitalized for an irregular heartbeat.
“The effects of using cannabis are seen within 15 minutes and last for around three hours. At lower doses, it is linked to a rapid heartbeat. At higher doses, it is linked to a too-slow heartbeat,” said lead researcher Dr. Rikinkumar Patel, a  in the department of psychiatry at Griffin Memorial Hospital in Norman, Okla.
Doctors need to ask new stroke and heart patients about their  to better inform their treatment options, both sets of researchers concluded.
“The risk of cannabis use linked to  in young people is a major concern, and physicians should ask patients hospitalized with arrhythmias about their use of cannabis and other substances because they could be triggering their arrhythmias,” Patel said.
However, both studies were observational and do not establish a direct cause-and-effect link between marijuana use and these conditions, Suri noted.

Explore further

More information: Harvard Medical School has more about marijuana and heart health.

Google collecting health data without patient knowledge

Google’s (GOOG -1%)(GOOGL -0.9%) Project Nightingale is collecting personal health data from Ascension facilities in 21 states without patient or doctor knowledge, according to WSJ sources.
The data includes lab results, diagnoses, and other information, including patient names and dates of birth.
The tech giant launched the project with the second-largest health system last year. Now, at least 150 Google employees have access to data on “tens of millions” of patients.
Privacy experts say Project Nightingale appears allowable under the federal HIPAA law, which lets hospitals share data with business partners if the information helps “the covered entity carry out its health-care functions.”
Google is partially using the data to build new software that uses machine learning to suggest care changes for an individual patient.

Regenxbio sues FDA over gene therapy clinical hold

Regenxbio is taking the FDA to court over a clinical hold. The lawsuit alleges the FDA imposed the hold “without notice or explanation” and has since “rebuffed” Regenxbio’s repeated requests for an explanation of the regulatory action.
In the lawsuit, news of which was reported by FDA Law Blog, Regenxbio argues the legislation that gives the FDA the power to issue clinical holds is unconstitutional. Regenxbio wants the court to pass a judgment that the law is unconstitutional and issue a permanent injunction to set aside the partial and full clinical holds affecting its pipeline.
The dispute began last month when, in Regenxbio’s telling of events, an FDA official told it two INDs were on a full clinical hold, effective immediately, without providing a reason. Regenxbio later learned the clinical hold is “due to issues associated with their delivery systems.”
Regenxbio wants a fuller explanation of the “issues” and “device concerns” that prompted the FDA clinical hold but claims it is being made to wait. The FDA allegedly told Regenxbio it would issue a letter outlining the deficiencies within 30 days, as is required by regulations, and later responded to “multiple communications” from the company by saying it will provide an explanation by Nov. 15.
The lack of warning and explanation are the main operational grievances identified in the lawsuit but the case gets at bigger topics with implications far beyond Regenxbio’s INDs. While some complaints raised in the lawsuit are specific to the FDA’s handling of Regenxbio’s INDs, the case also argues that Congress overstepped when it  empowered the agency to issue a clinical hold “for such other reasons as the [Health and Human Services] Secretary may by regulation establish.”
Regenxbio wants the court to order the legislation unconstitutional. The company is also seeking “any other relief that this Court deems just and proper,” reflecting its belief it has been harmed by the clinical hold.
“FDA’s actions have harmed, and continue to harm, Regenxbio. In addition to the reputational harm on Regenxbio caused by the clinical hold, Regenxbio is suffering actual and direct economic and competitive injury from the delay in development of these life-altering blindness treatments,” the lawsuit alleges.
The case is the second time this year that the FDA has been taken to court over a clinical hold. In February, Vanda Pharmaceuticals sought a legal fix to its partial clinical hold, arguing the FDA’s request for 9-month, non-rodent toxicity studies runs counter to scientific evidence. A federal judge returned the matter to the FDA in March. Vanda filed an amended complaint in May and a hearing is set for next month.

Aslan Pharma (-56%) lead drug flunks mid-stage study in biliary tract cancer

Thinly traded nano cap ASLAN Pharmaceuticals (ASLN -56.2%) craters on almost a 5x surge in volume, albeit on turnover of only 106K shares, in reaction to unsuccessful results from the first part of its Phase 2/3 clinical trial, TreeTopp, evaluating lead candidate varlitinib in patients with biliary tract cancer (BTC).
The study failed to achieve the primary endpoints of progression-free survival (PFS) and overall response rate (ORR). Specifically, median PFS in the treatment group was 2.83 months compared to 2.79 months for placebo. ORR was 9.4% versus 4.8% for control.
On a positive note, no new safety signals were observed.
One ray of hope is a subset of BTC patients who received the combination varlitinib and chemo agent capecitabine in a second-line setting. This group showed “improved efficacy.”
The data analysis is continuing.
Varlitinib is an orally available, reversible, small molecule pan-HER inhibitor. An investigator-initiated Phase 2 study in second-line HER1/HER2-positive gastric cancer is in process.