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Saturday, January 26, 2019

Google’s Effort to Prevent Blindness Hits Roadblock


Alphabet Inc.’s Google has developed artificial intelligence that can detect a condition that causes blindness in diabetic patients, though tests in India demonstrate the challenges of transferring such technology from the lab to the doctor’s office.
The tech giant’s Automated Retinal Disease Assessment tool is trained to diagnose diabetic retinopathy, a complication of diabetes, by reading images of patients’ retinas. Studies show that the artificial intelligence can be as effective as a doctor at identifying symptoms.
Google is testing ARDA in India where at least 60 million people have diabetes and often don’t know they should be screened for the eye condition. A shortage of ophthalmologists means reaching patients is difficult, and doctors say the technology could help to fill the gap.
Google is the latest tech firm to explore using AI in health care. Amazon.com Inc., International Business Machines Corp. and UnitedHealth Group Inc. sell software that mines patients’ records, and IBM developed AI that detects melanoma on images of skin.
By using technology similar to algorithms that recognize people or dogs in photos, ARDA detects signs of the illness–lesions, burst blood vessels and patches of yellow on the retina–and grades their severity.
“This is a technology that can make a really big difference,” said Lily Peng, a Google product manager and one of the leaders of the team developing ARDA at the company’s California offices.
While ARDA is effective working with sample data, according to three studies including one published in the Journal of the American Medical Association, a recent visit to a hospital in India where it is being tested showed it can struggle with images taken in field clinics. Often they are of such poor quality that the Google tool stops short of producing a diagnosis–an obstacle that ARDA researchers are trying to overcome.
The stakes are high. If diabetic retinopathy is caught early it can be kept at bay through monitoring and management of the diabetes, said R. Kim, an Indian ophthalmologist who runs the Aravind Eye Hospital in Madurai, Tamil Nadu, where Google is testing ARDA. More advanced stages need laser surgery that can stop progression. If it isn’t treated, the condition can cause blindness.
For Google, diabetic retinopathy was an ideal case study because experts agree on its symptoms. With skyrocketing rates of diabetes, India provided the right testing ground. As incomes have grown, so have citizens’ waistlines. The prevalence of the condition in India increased 64% from 1990 to 2016, according to government data.
“I am not proud to say, but India is becoming the diabetic capital of the world,” Dr. Kim said.
Yet the country has just 11 ophthalmologists for every million people, compared with 59 in the U.S., according to the International Council of Ophthalmologists. Training the number needed is “a race you can’t win,” he said.
In many cases, diabetic patients in India visit a doctor only when they have already lost some vision, Dr. Kim said. He hopes ARDA will reach more patients through doctors’ offices or pharmacies, pre-empting the need for his ophthalmologists to run screening camps in rural areas.
To create ARDA, Ms. Peng’s team obtained more than 1.6 million images of retinas that were each evaluated by ophthalmologists. Google used those graded images to train the algorithm. Now the team is grappling with how to make it work with low-quality images produced by the sort of equipment affordable in developing countries such as India.
On a November day in a telemedicine center at Dr. Kim’s hospital, ophthalmologists wearing headsets waited for 73 local eye clinics to connect patients in rural areas via webcam.
Ophthalmologist Anusha Arunachalan got a call from a clinic an hour from Madurai. A 39-year-old diabetic homemaker was having trouble seeing.
Six images sent by a clinic technician showed the patient’s retinas covered by pools of blood. Dr. Arunachalan diagnosed proliferative diabetic retinopathy–an advanced stage of the condition. Then Google gave it a try. It graded two of the six images as proliferative–though one was deemed of poor quality–and two others as severe. The tool was unable to grade two of the photos accurately because they were unclear.
While Dr. Arunchalan said it also was hard for her to read some of the images, “One [clear] image is enough for me. I don’t need three images” for each eye to make a diagnosis, she said.
Doctors at the telemedicine center said they often look at the clear parts of faulty images to make a diagnosis, while the algorithm sometimes can’t.
It isn’t a unique problem, said John Quackenbush, professor of computational biology at the Harvard T.H. Chan School of Public Health. Algorithms can be trained on sample images but real-world photos can be different.
“I don’t think it is insurmountable,” he said, on hearing about Google’s challenges.
Google is also testing the algorithm with another partner in India and one in Thailand and is working on making ARDA work with different-quality images, Ms. Peng said. But the challenge is also ethical.
If Google allowed the algorithm to make a diagnosis from blurred images, it could miss small lesions that appear in the early stages of the condition, she said. Google must decide how bad an image can be before ARDA refuses to grade it.
“It’s a trade-off. We want them to be able to use cameras that are a little harder to use but at some point it should move into something where it is ungradable,” Ms. Peng said.
Nonetheless, when ARDA gets a good image, it can identify early signs of the condition that doctors may have missed, Dr. Kim said.
Whereas ARDA does it in seconds, a human can take three minutes to grade an image plus the time taken to open it on a computer, Dr. Kim said. A busy doctor, he said, could very well miss tiny red lesions in a patient’s eye.

Gilead among low-debt stocks to buy, Barron’s says


After the first down year for U.S. stocks in a decade – and a quick snapback so far in 2019 – it may be a good time for investors to re-evaluate which kinds of stocks they want in their portfolios, and one good bet seems to be companies with low debt, Al Root writes in this week’s edition of Barron’s. With more cash than debt and high return on assets, Gilead Sciences (GILD), KLA-Tencor (KLAC), Teradyne (TER) and Gentex (GNTX) are his four picks.
https://thefly.com/landingPageNews.php?id=2854119

Civica Rx Starting With 20 Generic Drugs for Hospitals, Plans to Expand to 100+


Civica Rx was announced about a year ago, in January 2018. It is a not-for-profit generic drug company formed by five healthcare systems: U.S. Department of Veterans Affairs (VA),Intermountain Healthcare, Ascension, SSM Health and Trinity Health.
The company planned originally to offer 14 drugs in 2019. Because it has far exceeded its expectations for developing relationships with generic drug manufacturers and participating hospitals—approximately 800 now—it expects to offer 20. And within three to five years, believes it will offer up to 100 generic medicines.

Civica Rx has raised more than $160 million from its members, which along with the original groups, now includes HCA Healthcare, the Mayo Clinic, the Catholic Health Initiatives and more.
Civica Rx was created in response to severe shortages in the U.S. of hundreds of common generic drugs caused by consolidation of the generic companies, and manufacturing problems. Sometimes this has led to steep price increases, which is very much contradictory to why generics were developed. In particular, when a single company manufactures a generic drug, prices are kept very high.
“These are very, very old drugs that have been used not only for decades, some for almost a century,” Civica Rx chief executive officer Martin VanTrieste told Reuters. “When hospitals can’t have them, they are forced to cancel patient treatments or find alternative treatments. In most cases, that is suboptimal care or no care at all.”
In a study conducted at the University of Chicago on behalf of three healthcare organizations that was released this month, more than 90 percent of U.S. hospitals had to “identify alternative therapies to mitigate the impact of drug price increases and shortages.”
Hospitals working with Civica Rx agree to pay fees based on their size, as well as the cost of drugs purchased.
To date, Civica Rx hasn’t disclosed which manufacturers it is working with. It has only indicated its first drugs will be manufactured at sites in New Jersey, Pennsylvania and North Carolina already licensed to manufacture generic drugs. According to Reuters, Civica is negotiating long-term prices with the drug manufacturers in exchange for commitments from the member hospitals to buy the drugs for five to 10 years.
In the next four or five years, Civica Rx plans to buy or build its own manufacturing plants in order to stockpile six months of drugs to maintain availability. Its goal is also to ensure competition to keep prices low.
“We want to be very competitive,” VanTrieste told Reuters. “We want multiple manufacturers to make the products. We want our health systems to buy only half from us.”
Civica Rx also announced that another dozen healthcare systems have joined the organization. The new organizations include Advocate Aurora Health, Allegheny Health Network, Baptist Health South Florida, Franciscan Alliance, Memorial Hermann Health System, NYU Langone Health, Ochsner Health System, Sanford Health, Spectrum Health, St. Luke’s University Health Network, Steward Health Care and UnityPoint Health.
In prepared remarks, VanTrieste said, “Drug shortages have become a national crisis where patient treatments and surgeries are canceled, delayed or suboptimal. We thank these organizations for joining us to make essential generic medicines accessible and affordable in hospitals across the country.”
In a Reaction Data survey, 80 percent of almost 750 providers, payers and pharmaceutical companies said they are optimistic or cautiously hopeful Civica Rx will change the status quo. Pharmaceutical companies, however, were more skeptical the organization could overcome regulatory and logistical barriers, with only 29 percent believing it would be successful. About 38 percent of payers believed it will succeed.

Unanimous Supreme Court Ruling Could Create Patent Problems for Small Pharma


This week, the U.S. Supreme Court rejected Swiss pharmaceutical company Helsinn Healthcare SA’s claim that Teva Pharmaceutical violated patent rights when the Israel-based company released a generic version of its anti-nausea medicine, Aloxi.
The Supreme Court unanimously upheld a lower court’s ruling that had canceled the Switzerland-based company’s patent on Aloxi, a medicine used with chemotherapy patients. The Aloxi patent had been canceled due to a violation of a provision in U.S. patent law that “forbids sales of an invention before applying for a patent,” Reuters reported. Teva first began to sell its version of the anti-nausea medicine last year after the company had argued that Helsinn invalidated its patent, according to the report.

In 2001, Helsinn, which is a small company, struck a deal with another company to distribute Aloxi in the United States in order to defray its costs. The deal had been publicly announced in regulatory filings and press releases, Reuters said. For Helsinn, Aloxi was the company’s primary revenue generator. The drug provided hundreds of millions of dollars for the company annually, Reuters said.
Teva argued that the patent was invalid because the 2001 deal was struck two years before Helsinn first applied for a patent. That constituted a sale, Teva argued, according to the report. Helsinn argued that it had never disclosed its formula dosage or proof-of-concept details about Aloxi, which the court rejected. According to the America Invents Act of 2011, a company or inventor must file a patent application within one year of disclosing the products in a publication or other means available to the public.
In March 2018, Teva released its palonosetron hydrochloride injection to prevent nausea and vomiting that may occur as a result of receiving cancer chemotherapy with a moderate or high risk of causing nausea and vomiting.
The unanimous ruling by the Supreme Court could have some wide-ranging implications. As Reuters noted in its coverage, the ruling “could make it easier to cancel key patents, especially among smaller drugmakers.” The ruling could also widen the patent law provision “prohibiting the patenting of an invention if it has been on sale or offered to the public more than a year before the patent application was filed,” Reuters said.
With the ruling, larger companies could take advantage of the product lines of smaller companies. As the Boston Business Journal reported, many smaller companies do not have the capital to file patents on every new invention within that time frame and “often rely on partnerships and other deals with larger companies to advance their research pipelines.” The ruling has certainly gained its fair share of detractors. The Journal said MassBio, a trade organization in Massachusetts, said the ruling could hinder startups and innovation.

Friday, January 25, 2019

Muddy Waters calls Corcept report ‘extremely interesting,’ has no position


Carson Block’s Muddy Waters said via Twitter, “Extremely interesting article just out by @SIRF_Report on $CORT. Could rise to the level of #MoralityShorts – co markets a rare disease drug, which is prescribed in questionable amounts by MDs often receiving honoraria. Patient deaths in FAERS database…Because of patient deaths, sell-side analysts and funds in $CORT have a moral obligation to do REAL research to determine whether company is encouraging over / wrongful prescription. MW has no position.” Shares of Corcept Therapeutics are down 14%, or $1.96, to $11.85 in afternoon trading.

Franklin Resources reports 5.5% passive stake in Collegium Pharmaceutical


In a regulatory filing, Franklin Resources disclosed a 5.5% stake in Collegium, which represents about 1.82M shares. The filing does not allow for activism.

Franklin Resources reports 8.2% passive stake in Dermira


In a regulatory filing, Franklin Resources disclosed a 8.2% stake in Dermira, which represents about 3.5M shares. The filing does not allow for activism.