FDA Action Alert: Merck, Insmed and Antares Pharma

The U.S. Food and Drug Administration (FDA) has a few target action dates scheduled for this week, including one for Sunday, September 23, which was approved in late August. Let’s take a look.

The FDA gave Merck & Co. a PDUFA target action date of September 23 for its supplemental Biologics License Application (sBLA) for its anti-PD-1 drug Keytruda in combination with pemetrexed (Alimta) and platinum chemotherapy (carboplatin or cisplatin) as a first-line treatment for patients with metastatic nonsquamous non-small cell lung cancer (NSCLC). This was evaluated under Priority Review. The agency approved it for this indication and combination on August 20, 2018.

The supplemental application was based on overall survival (OS) and progression-free survival (PFS) data from the Phase III KEYNOTE-189 clinical trial.

“Keytruda is rapidly becoming a foundation for the treatment of appropriate patients with metastatic non-small cell lung cancer,” said Roger M. Perlmutter, president, Merck Research Laboratories, in a statement in August. “Today’s approval for the expanded label for Keytruda based on data from the KEYNOTE-189 trial is an important milestone, and reinforces our steadfast commitment to improving survival outcomes, and providing hope, for more patients with lung cancer.”

Bridge Water, NJ-based Insmed Incorporated has a target action date of Friday, September 28 for its New Drug Application (NDA) for ALIS (Amikacin Liposome Inhalation Suspension) for adults with nontuberculous mycobacterial (NTM) lung disease caused by Mycobacterium avium complex (MAC). It was granted Priority Review.

NTM is a rare and serious lung disease, which includes multiple symptoms like fever, weight loss, cough, lack of appetite, night sweats, bloody sputum, and fatigue. Though rare, its prevalence increased by about 8 percent a year from 1997 to 2007.

On August 7, the FDA’s Antimicrobial Drugs Advisory Committee voted 12 to 2 in favor of ALIS, as well as in favor of the surrogate endpoint of sputum culture conversion that was used in the Phase III CONVERT trial. However, in a separate vote, the committee voted against the safety and effectiveness of the drug in the broadest population of adults with NTM lung disease caused by MAC.

“We are very pleased by the outcome of today’s advisory committee meeting, which recognized the role ALIS may be able to play in addressing the significant unmet medical need among patients suffering from NTM lung disease caused by MAC, a chronic, debilitating and potentially fatal infection,” stated Will Lewis, Insmed’s president and chief executive officer.

Antares Pharma, based in Ewing, NJ, has a target action date of Saturday, September 29 for its investigational new drug for testosterone replacement therapy, Xyosted. The date was set in April, after the company resubmitted the drug application on March 29, 2018 after receiving a Complete Response Letter from the FDA.

The agency originally rejected the company’s NDA for Xyosted in October 2017. The CRL specified two deficiencies in the clinical data. The FDA indicated they were concerned the drug could cause a clinically problematic increase in blood pressure, as well as possible occurrence of depression and suicidality. There were no issues cited related to manufacturing or efficacy. As part of its resubmission, the company re-analyzed the data, but was not required to conduct additional clinical trials.

At the company’s second-quarter report on August 7, Robert F. Apple, company president and chief executive officer, said in a statement, “The recent launch of AMAG’s Makena auto injector product, the addition of a rescue pen development program to our business alliance pipeline and the potential for a late third quarter approval of our proprietary product Xyosted should continue to drive additional increases in revenue going forward….We are also focused on Xyosted launch planning as we continue to identify highly experienced sales representatives and stand ready to bring them on board contingent upon product approval on the September 29, 2018 target action date.”

https://www.biospace.com/article/fd1a-fda-action-alert-merck-insed-and-antares-pharma/

Some Cancer Cells Hide From Immunotherapy Treatments

Some cancer cells have a remarkable and frightening sense of self-preservation to avoid immunotherapy treatments.

That is the finding from a new study conducted by researchers at the Fred Hutchinson Cancer Research Center in Seattle. The study results, published in Nature Communications, took a close look at why immunotherapies do not always provide lasting treatments for some cancer patients.

The study focused on Merkel cell carcinoma patients and looked at why those patients who had been treated with immunotherapy would sometimes their cancers shrink at first but then come back. For the study, the Fred Hutchison researchers used a new technology that looked at how cancer cells change under the pressure of immunotherapy treatments.

Merkel cell carcinoma is a rare skin cancer caused by a common virus. About 20 percent of Merkel cell patients have an initial positive response to immunotherapy treatment but then relapse. It has been unclear why, Dr. Kelly Paulson, senior fellow at Fred Hutchison said.

By answering the question of “why,” Paulson said it will allow scientists to develop immunotherapies that can get toward long-term tumor control to make cancer a more chronic disease.

“Cancer is really tricky. We’re just starting to learn how tricky it is,” Paulson told BioSpace ahead of the study’s publication.

With the rise of immunotherapies like checkpoint inhibitors, Paulson said it was an exciting time to attempt to harness the body’s immune system in order to take out the cancer without affecting other cells in the microenvironment. Since the checkpoint inhibitors came onto market, she said they have been effective in certain types of cancer. She said with some melanomas, the checkpoint inhibitors have even eradicated some cases of metastatic cancer.

“There’s potential for the immune system to cure cancer. But, it’s challenging because not everybody gets that cure,” she said.

In the case of the Fred Hutchison study, the researchers studied the cancer cells from two patients Merkel cell carcinoma patients who initially responded to therapy, but saw their cancers return. The two patients were treated with a combination of a checkpoint inhibitor and a T-cell therapy that involved removing the cells from patients, multiplying them in a lab and then infusing them back into the patients. The T-cells were not engineered when they had been removed.

The patients responded well at first. Paulson said biopsies showed the T-cells got into the cancers and facilitated the tumor regression.

But then the cancer returned in both of them. In one patient, it was metastatic.

Paulson and colleagues used single-cell RNA sequencing to investigate the molecular changes in T cells, tumor cells and all other cells in the tumor microenvironment to see what had changed in the patients. And what they learned was both fascinating and a bit scary. They saw that the tumor was hiding from the T-cells, Paulson said.

“It was really quite tricky how the cancer came back.”

The tumor was able to accomplish this by removing one piece of human leukocyte antigens (HLA), a gene trio that allows T-cells to find the cancer cells. The single-cell RNA sequencing showed one piece of the HLA trip had been hidden by the tumor and that allowed the cancer cells to return without the T-cells noticing.

With that new knowledge in hand, Paulson and colleagues returned to the lab. They cultured cells from one of the patients and applied drugs already used clinically for other cancers that turned the cancer marker back on. The results from the in-vitro study will potentially be able to help other cancer patients who relapse following immunotherapy treatment.

Paulson said what she has learned is that a multi-pronged approach is the best approach to treating cancer than relying on a single treatment.

Paulson said they have known that other cancers have tricks to avoid destruction, but to her knowledge, this is the first time this particular trick with Merkel cell carcinoma has been reported.

“It’s a new variation on a theme that’s been known,” she said.

With the Fred Hutchison research now published, Paulson said it will likely lead to many questions about other cancers and their responses to immunotherapies. Paulson said researchers can begin to look hard at immunotherapy resistance across cancer settings in order to understand how cancer comes back after immunotherapy and why.

https://www.biospace.com/article/some-cancer-cells-hide-from-immunotherapy-treatments-study-finds/

RELX upgraded to Overweight from Equal Weight at Barclays

Barclays analyst Nick Dempsey upgraded RELX to Overweight and raised his price target for the shares to GBP 17.40 from GBP 17.10. The analyst views the current valuation as attractive.
https://thefly.com/landingPageNews.php?id=2794141

Amarin could have blockbuster after ‘stunning’ data, STAT’s Feuerstein says

https://thefly.com/landingPageNews.php?id=2794145

Ladenburg CEO Richard Lampen to Replace Phillip Frost as Chairman

Ladenburg Thalmann Financial Services Inc. (NYSE: LTS) announced today that its Board of Directors has appointed Richard Lampen, Ladenburg’s President and Chief Executive Officer, to serve as Chairman of the Board, replacing Dr. Phillip Frost. Adam Malamed, Ladenburg’s Executive Vice President and Chief Operating Officer, will join the Board of Directors.

Dr. Phillip Frost said, “I have decided to retire from the Ladenburg Board and will concentrate my efforts on OPKO Health and my philanthropic interests. As a long-term shareholder, I am confident in Ladenburg’s outlook and look forward to its continued growth and success.”

“We thank Phil for his service to Ladenburg and its shareholders over the past 14 years,” said Richard Lampen. “Ladenburg would not be where it is today without his many contributions, and his presence in the boardroom will be sorely missed.”

Mr. Lampen continued, “Our business is robust, and the company remains well-capitalized. Ladenburg’s book value exceeds $390 million, the Ladenburg entities hold approximately $250 million of cash, and the company is focused on building on its successes and delivering value to shareholders.”

https://www.streetinsider.com/Corporate+News/Ladenburg+Thalmann+%28LTS%29+CEO+Richard+Lampen+to+Replace+Phillip+Frost+as+Chairman/14630746.html

Needle-free blood draws at last?

The dreaded needlestick in the healthcare environment is a source of nightmares for many.  People have dreamed about getting rid of needles for years, not only to help patients relax when getting their blood drawn, but also to keep healthcare workers safe.

But even though there is legislation on the books—the Needlestick Safety and Prevention Act of 2000 encourages the use of safety sheaths and retractable needles and requires healthcare facilities to evaluate new sharps safety devices annually—injuries from sharps and needlesticks continue to occur.

NEEDLE-FREE BLOOD DRAWS

University Hospitals in Cleveland, Ohio, announced in July that it has implemented the PIVO needle-free device from San Francisco–based Velano Vascular at UH Cleveland Medical Center for inpatient blood draws.

“As an institution, we continually look for innovative new technologies that improve the delivery and quality of care we provide,” Daniel I. Simon, MD, president of UH Cleveland Medical Center, says in a statement. “As caregivers, we strive to serve our patients in the most humane and personal way possible. This new procedure makes it possible for us to do both, eliminating the pain and anxiety associated with blood collection while advancing our own high standards and practices.”

Two other hospitals, Griffin Hospital in Derby, Connecticut and Brigham & Women’s Hospital in Boston, are also testing the PIVO device.

In typical practice, an IV needle is used to puncture the skin. That needle is then withdrawn and replaced with a plastic tube that becomes soft and almost noodle-like over time. While a “noodle” is fine for injecting fluids and medications into a patient, it’s bad for drawing fluids out of a patient, as the negative pressure of suction causes the tube’s soft walls to collapse. Also, clots that form at the ends of the IV catheter can disrupt the blood testing process.

The PIVO uses a narrower-gauge, stiffer tube inside the existing IV tube for collecting a blood draw. The device is used once and then thrown away, after which the IV catheter is reattached to the bag containing whatever fluids were being delivered to the patient prior to the blood draw. PIVO allows practitioners to extract high-quality blood samples from the vein, eliminating the need for multiple needlesticks.

The device was created by Velano Chief Executive and co-founder Eric M. Stone and President Pitou Devgon, MD. Velano won FDA approval for the PIVO in 2015; it has also obtained two U.S. patents for the device, according to published reports, with additional applications outstanding in the U.S. and abroad. Velano has publicly acknowledged receiving a total of $8.5 million in investments to improve the device.

The adoption of PIVO at UH’s flagship academic campus follows evaluation of the technology and the procedure in multiple UH Cleveland Medical Center inpatient units, the hospital said in a statement.

“Our evaluation and collaboration proved that PIVO delivers high-quality blood draws in an elegant manner that enhances the patient-practitioner relationship, reduces rejected blood samples, and provides an alternative to accessing central lines for blood collection,” said Cheryl O’Malley, vice president of patient care services and nursing at UH Cleveland Medical Center. “We are excited to bring this procedure and technology to our entire academic hospital, especially for our most vulnerable patients like those at UH Rainbow Babies & Children’s.”

SAFER SHARPS SLOW TO EVOLVE

More than 400 million blood draws occur annually in hospitals in the U.S., informing as much as 70% of all clinical decisions. Many of these are conducted in a hospital setting on patients that receive as many as three blood draws daily. This number of daily draws can increase dramatically for the 30% of U.S. hospital patients that are classified as “difficult venous access,” or DVA, due to obesity, age, or disease.

Stone is a Northeast Ohio native and former UH Rainbow Babies & Children’s Hospital patient. “As a chronic disease sufferer and over the course of multiple hospitalizations as a teenager, I developed a clinical fear of needles,” said Stone. “My personal experience as a patient has informed our person-centered mission at Velano to enable more humane care. Coming full circle, back to UH and Rainbow, to make this technology a national standard of care will enable our children and their parents to have their blood drawn in a gentler fashion.”

It may have important benefits for healthcare staff, too.

In July 2017, the Houston-based group International Safety Center released surveillance data from hospitals in 2015 that showed a marked increase in injuries from sharps and needlesticks sustained by training physicians (i.e., residents and interns) compared to 2014, and an overall increase in injuries sustained in the operating room, along with an unexpected decrease in the use of safety-engineered medical devices.

And, according to OSHA, up to 5.6 million workers in the U.S. are at risk of exposure to bloodborne pathogens, such as HIV and hepatitis, because they use needles and other sharps like scalpels as part of their everyday job. In fact, every year, about 1 million workers in hospital and clinic settings suffer a needlestick or other sharps-related injury.

One well-known example of this is the experience of nurse Karen Daley. In 1998, she was working in the ED at a Boston-area hospital and was stuck by a needle protruding from a full sharps container. As a result, Daley contracted both HIV and Hepatitis and had to end her career in the ED. She has since become an advocate for needlestick safety and lobbied for the 2000 Needlestick Safety and Prevention Act. She is also former president of the American Nurses Association.

Safe in Common, a nonprofit organization based in York, Pennsylvania, issued a list of guidelines in 2013 that serves as a “wish list” of attributes for sharps safety. Established in 2010, SIC is an organization of healthcare professionals and advocates that work to raise awareness of needlestick injuries and save lives of healthcare workers.

The guidelines, titled “The Top Ten Golden Rules of Safety,” were released at the Association for Professionals in Infection Control and Epidemiology conference in Fort Lauderdale, Florida. Specifically, the guidelines seek to make needlestick injuries a “never event,” an incident so rare that it almost never happens, by lobbying for sharps that are easy to use in even the most distracting environments. In addition, safety devices should be activated automatically so that they’re safe and easy to use with one hand. Sharps should also be “rendered safe prior to removal or exposure to the environment,” should not cause additional harm or discomfort to the patient, and should not add to the already-high cost of medical waste.

https://www.healthleadersmedia.com/nursing/can-nurses-look-forward-needle-free-blood-draws

India launches ‘Modicare’, world’s biggest health scheme

India on Sunday launched the world’s biggest health insurance scheme which Prime Minister Narendra Modi said would cover some 500 million poor people.

The programme, dubbed “Modicare”, promises health cover worth 500,000 rupees ($6,900) to every poor family to treat serious ailments.

The scheme is expected to cost the central and 29 state governments $1.6 billion per year in total. Funding will be increased gradually according to demand.

Modi handed medical cards out at the launch in Ranchi, capital of the eastern state of Jharkhand, calling it a historic day for India.

He called the scheme “a big step towards providing good quality and accessible healthcare to the poor of India. Over 100 million families will benefit.”

India’s overburdened public health system is plagued by a shortage of hospitals and doctors and most people use private clinics and hospitals if they can afford to.

But a private consultation can cost 1,000 rupees ($15), a huge sum for millions living on less than $2 a day.

More than 60 percent of the average family’s spending goes on medicines and healthcare, the government estimates.

Experts have praised the latest programme but say it should have included primary day-to-day healthcare instead of just secondary and tertiary care for more serious and long term treatment.

“Modicare does not extend to primary healthcare, which, we believe, is the weakest link in the provision of public health in India,” Rajiv Lall and Vivek Dehejia of the IDFC Institute think-tank said in a column for the Mint newspaper.

“The crucial point is that poorly delivered primary care inevitably increases the burden on health and finance at the secondary and tertiary levels down the line,” they said.

 Explore further: India unveils healthcare for 500 million of its poorest

https://medicalxpress.com/news/2018-09-india-modicare-world-biggest-health.html