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Friday, April 5, 2019

U.S. forces Chinese divestiture in health data startup PatientsLikeMe

Real-world data gatherer PatientsLikeMe has to shop for a new buyer—and quickly—after the Trump administration ordered a Chinese company to divest its majority stake, according to a report from CNBC.
In 2017, PatientsLikeMe partnered with the Shenzhen, China-based iCarbonX—a genomics data firm supported by the conglomerate Tencent—and raised more than $100 million in a series C round with iCarbonX serving as lead investor.
iCarbonX agreed to provide multi-omics sequencing services, while PatientsLikeMe would serve as “a cornerstone” of its health technology collaboration, which aimed to merge and analyze biological and patient-generated information using artificial intelligence.
The Cambridge, Massachusetts-based PatientsLikeMe links together about 700,000 people with those who have similar conditions to share health experiences and gather data for research studies. Other companies participating in iCarbonX’s alliance included SomaLogic, HealthTell, AOBiome, GALT, Imagu and Robustnique, according to a release.
However, the Treasury Department’s Committee on Foreign Investment in the United States (CFIUS) has been scrutinizing Chinese investments in American companies.
CFIUS ordered the divestiture under a 2008 statute that allows the president to review and block any merger that could result in a foreign person or company controlling a U.S. company. That was expanded last year to include foreign investments and minority stakes, in addition to takeovers, the article said.
While CFIUS previously focused on multibillion-dollar international acquisitions, the actions singling out a small company could have harsh effects on the startup sphere by chilling international investment.
CNBC reported that Chinese expenditures in U.S. businesses have dropped 90% in the past two years, from $46 billion in 2016 to $4.8 billion in 2018, according to data from the Rhodium Group, which said another $20 billion in divestitures is still pending.

FDA declares 40 generics free of carcinogens as ‘sartan’ recalls continue

As recalls on blood pressure drugs continue to plague drugmakers, the FDA declared a slate of 40 generic pills safe to use.
On Thursday, the agency released a list of 40 generic angiotensin II receptor blockers (ARBs) that are free of three potentially carcinogenic compounds linked to various “sartan” drugs, including valsartan and losartan.
The FDA launched a global recall in 2018 after a U.S. drug manufacturer found high levels of N-nitrosodimethylamine (NDMA) in the valsartan active ingredient it had bought from a Chinese supplier. Since then, the FDA discovered that NDMA, N-Nitroso-N-methyl-4-aminobutyric acid (NMBA) and NDEA—all considered unsafe at certain levels—can be created during sartan drug manufacturing under certain conditions.

The first global recall included all non-expired generic valsartan sold by Major Pharmaceuticals, Teva and Huahai’s U.S. subsidiary, Solco Healthcare, as well as valsartan/hydrochlorothiazide (HCTZ) made by Teva and Solco.
The recall later expanded to other “sartan” products as impurities turned up in the irbesartan API produced by India’s Aurobindo and in losartan products made using an API from China’s Zhejiang Huahai Pharmaceuticals.
With an investigation underway, the FDA’s top two drug officials reiterated in a joint statement that generics with carcinogen levels higher than the accepted limit would be temporarily distributed to prevent a shortage of losartan, which is used to treat high blood pressure and prevent heart failure.

Outgoing FDA Commissioner Scott Gottlieb and Janet Woodcock, director of the Center for Drug Evaluation and Research, said agency scientists believe using the tainted drugs temporarily wouldn’t raise cancer risks in a “meaningful” way. “After careful evaluation of safety data and consideration of the benefits and risks to patients, we think it’s critical that patients have access to these drugs while impurity-free losartan is manufactured,” the Thursday statement said.
Gottlieb and Woodcock said they expected carcinogen-free products to replenish the U.S. supply of losartan within six months.
“We want to reassure patients that we strongly believe the risks, such as stroke, of abruptly discontinuing these important medicines far outweighs the low risk associated with continuing the medications with these impurities,” they said.
After the recalls, a suite of lawsuits were filed against drugmakers cited by the FDA, including Indian drugmaker Aurobindo and Huahai.

In October, Huahai told the Shanghai Stock Exchange that it faced lawsuits in four states over its production of tainted valsartan.
In a federal suit in Florida, consumers accused Walmart, Aurobindo, U.S. drugmaker ScieGen Pharmaceuticals and distributor Westminster Pharmaceuticals of producing and selling tainted irbesartan that may have exacerbated health conditions.
In an attempt to begin cleaning up the valsartan market, the FDA hustled through a new valsartan generic from India’s Alkem Laboratories last month. The agency said Alkem’s Diovan copy was free from NDMA and NDEA.

Why your doctor might ignore your DNR — and it’s perfectly legal

While seated in the waiting room of a Florida outpatient surgery center, an 82-year-old patient received a nasty surprise. The receptionist asked him to sign a form stipulating that the facility would disregard his properly executed DNR [do-not-resuscitate] order.
Specifically, the form stated that the center would ignore his end-of-life wishes “regardless of the contents of any advance directives/living wills.” The patient was angry and confused.
There’s a business rationale for health care facilities to proclaim their indifference to a patient’s wishes. By keeping people alive at all cost, they avoid potential liability for a mishap before, during or after a medical procedure.
But are they allowed to ask a patient awaiting surgery to sign such a form?
“It is legal but it may not be ethical,” said Craig Klugman, a professor of bioethics at DePaul University in Chicago. “It is done out of fear of harming patients and the liability.”
He notes that several medical associations have concluded that asking patients to sign blanket DNR overrides is not appropriate. Instead, the provider should confer with the patient beforehand and hash out a plan if things go awry.
In practice, however, such conversations rarely occur. In the run-up to surgery, harried providers may lack the time or inclination to raise this sensitive issue. And patients might assume that as long as they’ve completed their advance directives and their doctor has signed their DNR order, there’s nothing further to discuss.
There’s an understandable medical reason why some facilities disregard DNRs. Say a procedure involves anesthesia and temporary cardiac abnormalities or other serious problems arise. Anesthesiologists and surgeons can in many cases “pretty easily reverse” such adverse events, Klugman says, thus bringing you back to life before you know it.
“You might have an interaction with the anesthesia drug,” he said. “It can have nothing to do with your underlying disease,” and resuscitating you poses a manageable risk. So it’s no wonder facilities want you to acknowledge in advance that they can intervene in such instances.
Always ask ahead of time if a hospital, outpatient surgical center or other provider will honor your DNR order. Know their policy in advance so that you’re not caught off guard when they ask you to sign something just before they wheel you into the operating room.
“You have to be willing to negotiate,” Klugman said. “When I’m handed an informed consent form, I cross things out and add things in,” such as limiting the institution’s ability to share his medical information with third parties without his permission.
It’s also important to understand what documents you need to convey your end-of-life wishes. Laws and protocols vary by state.
Terms such as “advance directive,” “living will” and “health care power of attorney” can have subtle differences depending on where you live. In addition, about two-thirds of states have some version of a “POLST” form that indicates what medical treatments you want (or don’t want) in an emergency, Klugman says. In some states, physicians and other providers must honor a valid advance directive or face disciplinary action.
Because you cannot anticipate every conceivable scenario when you might get resuscitated or receive life-altering care, think ahead. Write an expansive letter describing under what conditions you want to be kept alive (to play with your grandkids?, eat and drink on your own?, cheer your favorite sports team? etc.).
Use the letter as an opportunity to share your values and end-of-life philosophy. For instance, consider whether you prioritize pain management over mental clarity (or vice versa) if battling a major illness. Sign and date the letter and share it with your family, medical providers and anyone else involved in your care.
“Be as clear as you can be with your written documents and with your loved ones so that your health care agent can express your wishes on your behalf,” said Robyn Shapiro, an attorney and founder of the Health Sciences Law Group in Fox Point, Wis. “Be clear with your doctor as well.”
An often-overlooked step involves completing a psychiatric advance directive, especially if you have a mental illness. Otherwise, a crisis can leave you dependent on others to make life-or-death decisions for you.
“A psychiatric advance directive can be a different form or part of standard advance directives,” Shapiro said. “If you have a history of mental illness, you can say if you want a loved one to enter you in a clinical [drug] trial or get electroshock therapy.”

Janssen Gets Euro Priority Tag for CAR-T Therapy JNJ-68284528

The Janssen Pharmaceutical Companies of Johnson & Johnson today announced that the European Medicines Agency (EMA) has granted a PRIME (PRIority MEdicines) designation for the companys investigational B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CAR-T) therapy, JNJ-68284528 (JNJ-4528). PRIME offers enhanced interaction and early dialogue to optimise development plans and speed up evaluation of cutting-edge, scientific advances that target a high unmet medical need.1
The PRIME designation of this novel BCMA CAR-T therapy highlights the value of regulatory innovation in the European Union, said Sjaak Bot, Vice President, Head EMEA Regulatory Affairs at Janssen Biologics B.V. We hope to bring this important advance to patients as quickly as possible and this PRIME designation, the first for Janssen, marks an important milestone towards potential market approval.
The PRIME designation is based on results from the Phase 1/2 LEGEND-2 study (NCT03090659) evaluating LCAR-B38M CAR-T cells, sponsored by Nanjing Legend Biotech Co.,2 and the Phase 1b/2 CARTITUDE-1 study (NCT03548207) evaluating JNJ-4528, sponsored by Janssen and being conducted in collaboration with Legend Biotech USA Inc.3 Results from the LEGEND-2 study were presented at the American Society of Hematology (ASH) 2018 annual meeting.4 Results from the CARTITUDE-1 study will be presented in the future.

Abiomed: Cardiogenic Shock Survival Up Significantly since Impella FDA PMA OK

Three years ago this week, Abiomed’s (NASDAQ: ABMD) Impella heart pump received its FDA PMA approval for AMI cardiogenic shock.
At the time of Impella’s FDA PMA approval, the cardiogenic shock survival rate to explant in the Impella Quality Assurance (IQ) Database was 51% in the United States1. Today, Impella heart pumps, combined with the adoption of best practices, which include the use of Impella pre-PCI, have contributed to a significant increase in cardiogenic shock survival and native heart recovery. New data from the IQ Database on nearly 5,000 patients treated between April 2018 and March 2019 show an increase in survival from 51% to 67%2, a relative increase of 34% in survival.
Since FDA PMA approval, Abiomed has collected data on nearly 100% of U.S. Impella patients in the observational IQ Database. This clinical data, combined with the FDA post-approval studies embedded in Abiomed’s prospective cVAD Study, helped identify and validate best practices for Impella use associated with improved survival and native heart recovery. These best practices, including use of Impella pre-PCI, reduction of inotropes, early identification of shock, and hemodynamic monitoring with pulmonary artery catheters, have now been validated in multiple publications: Journal of Interventional Cardiology, 2014: Placement of Impella pre-PCI is associated with more complete revascularization and improved survival to discharge in the setting of AMI cardiogenic shock (65% with Impella placed pre-PCI vs. 41% post-PCI, p=0.023).
American Journal of Cardiology, 2017: Initiation of Impella before PCI and prior to initiation of inotropes or vasopressors is independently associated with improved survival. Survival to discharge was 68%, 46%, 35%, 35%, and 26% for patients requiring 0, 1, 2, 3, and 4 inotropes before mechanical circulatory support, respectively

Intercept to Present on 1st Successful Phase 3 for Liver Fibrosis Due to NASH

Intercept Pharmaceuticals, Inc. (Nasdaq: ICPT), a biopharmaceutical company focused on the development and commercialization of novel therapeutics to treat progressive non-viral liver diseases, today announced that multiple OCA abstracts will be presented at the International Liver Congress 2019, the 54th Annual Meeting of the European Association for the Study of the Liver (EASL), in Vienna, Austria from April 10, 2019 through April 14, 2019.
‘We are thrilled to be presenting our groundbreaking Phase 3 REGENERATE results during the Opening Ceremony and General Session of the 2019 International Liver Congress, which promises to be a watershed event for the hepatology community,’ said Mark Pruzanski, M.D., President and Chief Executive Officer of Intercept. ‘In addition to REGENERATE, we will be presenting a late-breaking poster on a placebo-controlled study of OCA showing physiologic improvement of liver function in NASH patients with fibrosis, as assessed by the HepQuant quantitative liver function test. In PBC, we are looking forward to a late-breaking oral presentation of an investigator-initiated study which showed that the addition of bezafibrate to OCA improved both cholestasis and pruritus, underscoring the rationale for our plan to develop a fixed dose combination of these two agents.’

LivaNova reports preliminary Q1 revenue $251M, consensus $264.58M

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