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Friday, May 31, 2019

Medical Marijuana ‘Useful Tool’ For Cancer Treatment: ASCO Study

Medicinal marijuana has long been a topic of controversy in the medical community. Issues about weed range from its legality to whether or not enough extensive studies have been done.
However, many experts acknowledge the benefits of medicinal marijuana and even feel that it could be a useful tool in treating cancer.
A study presented by the University of Colorado Cancer Center at the ASCO, American Society for Clinical Oncology, Annual Meeting 2019 showed that while 73 percent of surveyed oncology providers believe in the benefits that medicinal marijuana provides for cancer patients, only 46 percent of them were comfortable recommending it to patients. Survey respondents included 53 registered nurses, 48 specialized oncologists, 47 physicians, 17 pharmacists, and 7 oncology providers.
According to the report, 79 percent of survey respondents expressed that while they were uncomfortable prescribing medicinal marijuana as a tool for cancer treatment, additional educational programs during training and as continuing medical education courses could increase how comfortable they were in prescribing medicinal marijuana. Interestingly enough, around 68 percent of survey respondents reported that they received information about medicinal marijuana from their patients.

This discomfort could stem from the fact that most providers don’t train in states where medicinal marijuana is legal. Adapting the healthcare education to include medicinal marijuana, and providing training on medicinal marijuana could help to increase the comfortability of current providers in prescribing medicinal marijuana as a useful tool for cancer treatment.
Providers also brought up another issue they had with prescribing medicinal marijuana in the form of legal and regulatory concerns. Those working in academic medical centers expressed concerns about prescribing medicinal marijuana as it could jeopardize federal funding since marijuana remains to be a U.S Drug Enforcement Agency Schedule 1 drug.
Providers reported that if additional clinical data regarding the effectiveness of medicinal marijuana were provided, and if there were to be endorsed guidelines that would dictate the conditions and situations in which medicinal marijuana is to be prescribed, they would feel more at ease prescribing medicinal marijuana.

While there are numerous cancer medication used to treat different symptoms, medicinal marijuana has the benefit of treating numerous symptoms simultaneously. Medicinal marijuana has been found to be especially helpful to cancer patients undergoing chemotherapy as it helps to quell many of the side effects that come with undergoing the treatment.

ASCO: Primary care has crucial role in diagnosis, survival of cancer patients

Diagnosis, screening, risk reduction, managing comorbidities, helping to coordinate specialty care, long-term toxicities, palliative care, survivorship, and vaccination are just a few of the roles for primary care physicians related to the diagnosis and care of cancer patients.
The message, delivered today during a panel discussion at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, sought to address myriad of challenges faced when coordinating care after a person is first diagnosed with cancer, during treatment, after care, and in survivorship.
“We are on the front lines for diagnosing cancer, coordinating treatment phases leading to survivorship, and end-of-life care,” says Larissa Nekhlyudov, MD, MPH, an internist and survivorship care provider at Dana-Farber/Brigham and Women’s Hospital in Boston.
Piyush Srivastava, MD, an oncologist for Kaiser Permanente in Walnut Creek, Calif., says survivorship studies have shown that Stage I and Stage II cancer patients are more likely to die from hypertension or modifiable risks like cigarette smoking than cancer. Who would you prefer to manage high blood pressure, diabetes, or other chronic diseases? “The answer is that primary care physicians need to be an active member of the cancer-care team,” he says.
Consider that every 10 additional primary care physicians per 100,000 of population are associated with 51.5 days of additional life expectancy, versus 19.2 days for additional life expectancy with specialists. (JAMA Intern Med. 2019; 179(4) 506-514)
Every 10 additional primary care providers per 100,000 of population are also associated with reduced cardiovascular, cancer and respiratory mortality.
As oncologic therapies advance, it signals a need to adopt a more collaborative approach to patient care, during treatment and when a patient enters remission.
Trevor Jolly, MBBS, a medical oncologist at the University of North Carolina at Chapel Hill, adds the primary care physician should serve as the medical quarterback. He encourages primary care physicians and oncologists to pick up the phone and communicate about cases and better collaborate on treatment decisions, especially for those patients undergoing chemotherapy or radiation.
“During treatment, patients tend to rely on the specialist,” Jolly says. “But in my office, we are referring back to the primary care physician.”
Elizabeth Shiff, a cancer survivor and patient advocate at the University of Cincinnati, adds, when a patient is diagnosed with cancer, he or she is only thinking about next steps in the treatment plan. “It is important,” Shiff says, “to stress to the patient that his or her care will be like a triangle—between the oncologist, primary care physician, and patient. “Empower your patients with communication about the treatment plan and the role of providers,” she adds.
Jolly agrees. “I think we need to have a more collaborative approach where treatment decisions are shared, especially with comorbidities and when hypertension or diabetes is uncontrolled.”
As cancer therapies advance, survivorship numbers have been climbing as well. Consider that 1.7 million new cases of cancer are diagnosed each year, but there are 16.9 million survivors. It signals a growing need for improved collaboration between oncologists and primary care physicians.

ASCO 2019 Preview: Presentations to Keep An Eye On

American Society of Clinical Oncology (ASCO) meeting is always an exciting week in the pharma industry as multiple companies showcase their clinical research into various cancers.
The excitement gets underway on Friday in Chicago as companies unveil data from recent trials that could potentially change the way in which providers treat cancer. Below are a few presentations that will bear watching at ASCO.
Novartis – Swiss pharma giant Novartis will present data from across its oncology portfolio at ASCO for multiple cancers, including breast cancer, melanoma, lung cancer and other solid tumors. Novartis will walk into ASCO with its head held high after winning approval from the U.S. Food and Drug Administration for a first-of-its-kind breast cancer treatment. The FDA gave the nod to Piqray, the first and only treatment specifically for patients with a PIK3CA mutation in HR+/HER2- advanced breast cancer. Piqray works by inhibiting the PI3K pathway, predominantly the PI3K-alpha isoform, to address the effect of PIK3CA mutations. Piqray (alpelisib, formerly known as BYL719) in combination with fulvestrant, was approved by the FDA for the treatment of postmenopausal women, and men, with hormone receptor-positive, human epidermal growth factor receptor-2 negative (HR+/HER2-),PIK3CA-mutated, advanced or metastatic breast cancer. Novartis will present data from the Phase III SOLAR1 trial which earned Piqray its FDA approval.

The company will also provide additional clinical analyses from its key radioligand therapy – Lutathera, the first ever approved Peptide Receptor Radionuclide Therapy. Lutathera was approved in January for the treatment of somatostatin-receptor positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), an orphan disease.
Oncoceutics, Inc. – Philadelphia-based Oncoceutics, Inc. will showcase data from its ongoing trial assessing ONC201 in adult recurrent H3 K27M-mutant glioma. The oral abstract session presentation, entitled “Single agent ONC201 in adult recurrent H3 K27M-mutant glioma” will describe the clinical experience of ONC201, in adults with recurrent H3 K27M-mutant glioma. ONC201 is an orally active small molecule DRD2 antagonist. The presentation will discuss a cohort of adults with H3 K27M-mutant glioma patients who have received ONC201 after failure of available therapies. The results will include assessments of radiographic response, progression-free survival and overall survival, as well as safety and clinical benefit. In addition, there will be an update on ONC201 in previously irradiated pediatric H3 K27M-mutant glioma that will be presented in a poster session.
OncoNano Medicine, Inc. – Texas-based OncoNano will share full data from its first-in-human study of ONM-100, an intravenously administered imaging agent. The agent was well tolerated and enables fluorescent visualization of tumor-positive margins and occult disease in solid tumors during surgery, the company said. Low pH is a well-known indicator of diseased tissue and ONM-100 has the potential to act as a broadly indicated tumor agnostic imaging agent, OncoNano said. When used by surgeons, ONM-100 is delivered to the tumor and fluoresces in the acidic tumor microenvironment. This enables surgeons to visualize the tumor during surgery using existing near infrared surgical cameras. OncoNano recently concluded a Phase 1 clinical trial for ONM-100.

AstraZeneca – British pharma giant AstraZeneca will also showcase some of its oncology assets during the conference. Of note is data regarding the company’s Phase III POLO trial showing its market-leading PARP inhibitor Lynparza (olaparib) as a possible first-line treatment in metastatic pancreatic cancer (mPC) patients with a germline BRCA mutation. In February, the company announced the data from the late-stage trial that showed Lynparza provided a statistically significant and clinically meaningful improvement in progression-free survival (PFS) as first-line maintenance therapy. Lynparza received Orphan Drug designation from the FDA for pancreatic cancer in 2018, and AstraZeneca plans to file for approval in the second half of 2019.
Another study of note that AstraZeneca will share is the PACFIC trial demonstrating Imfinzi three-year overall survival in Stage III non-small cell lung cancer. Imfinzi is the first immunotherapy approved for stage III lung cancer. Last fall AstraZeneca released results that showed Imfinzi (durvalumab) significantly improved OS. Regardless of PD-L1 expression compared to placebo, the drug decreased the risk of death by 32 percent, the company said. Data also showed positive results in progression-free survival.

ASCO 2019 day one

Exclusive live coverage from day one of the American Society of Clinical Oncology’s annual meeting in Chicago.
• To view all of our coverage from the preeminent cancer event, produced in association with Kantar Health, as well as additional content, visit the Spotlight on ASCO 2019 and the future of oncology
ASCO 2019 kicks off this year with a strong focus on prostate cancer, as several pharma companies are attempting to find ways to treat the disease earlier, or find better ways to prevent it spreading.
Key readouts to look for on Friday 31st May:
  • Data from Johnson & Johnson’s Erleada (apalutamide) in patients with metastatic castration-sensitive prostate cancer (mCSPC). This will be the first time that we get the chance to see detailed data from the phase 3 TITAN study.
  • AstraZeneca and Merck & Co have data from the phase 2 TOPARB-B trial, testing their PARP inhibitor Lynparza (olaparib) for metastatic castration resistant prostate cancer.
  • AstraZeneca and Merck & Co are also due to present data from a phase 3 study testing Lynparza in pancreatic cancer, in patients with an inherited BRCA gene mutation.

View the live coverage from day one at ASCO 2019 below (the live blog may take a few seconds to load) and we will also have live coverage from day two at ASCO:
Last Updated: 2 hours ago
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That’s a wrap (for day one)
And that’s it for our live coverage of day one at ASCO 2019, presented in association with Kantar Health.
We’ll be back tomorrow with expanded news coverage of some of today’s key events as well as a live blog from day two of ASCO 2019.
In the meantime if you are on site tomorrow there’s an interesting looking session on social media for authors from 2-3pm.

Grail, deep-pocketed startup, shows ‘impressive’ early cancer blood test data

Could a blood test detect cancer in healthy people? Grail, a Menlo Park, Calif.-based company, has raised $1.6 billion in venture capital to prove the answer is yes. And at the world’s largest meeting of cancer doctors, the company is unveiling data that seem designed to assuage the concerns and fears of its doubters and critics. But outside experts emphasize there is still a long way to go.
The data, from a pilot study that Grail is using to develop its diagnostic before running it through the gantlet of two much larger clinical trials, are being presented Saturday in several poster sessions at the annual meeting of the American Society of Clinical Oncology. The data show that the company’s test can detect cancer in the blood with relatively few false positives and that it is fairly accurate at identifying where in the body the tumor was found. Another abstract seems to show that the test is more likely to identify tumors if they are more deadly. One big worry with a cancer blood test is that it would lead to large numbers of patients being diagnosed with mild tumors that would be better off untreated.
“The progress of the technology is impressive,” said Dr. Len Lichtenfeld, the acting chief medical officer of the American Cancer Society. But he also urged caution. “Grail is one organization that is pursuing this goal. We will get there. But we still have to prove the technology, and we still have to learn how to apply the technology.”
Dr. Eric Topol, the director and founder of the Scripps Research Translational Institute, called the results “encouraging” and commented that Grail is “trending toward credibility.” He agreed that if these early results hold up, the blood test could be more predictive than existing screening tools, like prostate-specific antigen or mammography. But he, too, emphasized the need for much more research. “All of this requires a large, prospective assessment,” he wrote via email.
Grail is running a preliminary study called the Circulating Cell-Free Genome Atlas (CCGA), which is being conducted in 15,000 patients. The goal from the beginning was to use this study to optimize a diagnostic test. This would then be tested in two more studies: one of 100,000 women enrolled at the time of their first mammogram, and a second of 50,000 men and women between the ages of 50 and 77 in London who have not been diagnosed with cancer. These huge studies are one reason Grail has raised so much money.
But the data being reported at the ASCO meeting are from a tiny sliver of that first study: an initial analysis of 2,301 participants from the training phase of the sub-study, including 1,422 people known to have cancer and 879 who have not been diagnosed. These data are being used to pick exactly what test Grail will run.
Dr. Steven Joffe, the chief of the division of medical ethics at the University of Pennsylvania Perelman School of Medicine, called it “important and necessary work, but very different from the envisioned use as a screening tool.”
The first big surprise is exactly what test the company is using. When it was spun out of DNA sequencing giant Illumina in 2016, Grail was focused on genes. The idea was that little bits of DNA shed by cancer cells could be detected in the blood. But Grail is now not looking at the genes themselves, but patterns called methylation, which is used by the body to change how the genetic code is read.
“You start out with a few cells, but then they become tremendously differentiated into brain cells, heart cells, skin cells, all of those things,” said Dr. Alex Aravanis, Grail’s head of research and development. “Methylation is the fundamental signal that determines those cell identities and cell fates.”
Grail had previously presented strategies of using DNA in the blood to detect cancer: sequencing the entire genetic code, or a targeted panel of genes, or using methylation. Aravanis said that methylation was not only the most accurate method, but the best at telling where the tumor originated — whether it was breast cancer, lung cancer, or pancreatic cancer, for instance, that the patient had.
The test was set up so that it would have a 99% specificity — meaning that for every 100 people told they had cancer, 1% would actually not have the disease. The test could detect 34% of cancers at stage 1, when the cancer is least risky, 77% at stage 2, and 84% at stage 3. For 94% of patients, the diagnostic gave the tissue of origin of the test, and it was right nine times out of 10.
Ability to correctly identify where the cancer was varied by tumor type. At 99% specificity, the test identified 59% of early-stage lung cancers, 74% of colorectal cancers, and 78% of pancreatic cancers. The test got better when later-stage cancers were included: identifying location for 92% of lung cancers, 97% of colorectal cancers, and 79% of pancreatic cancers.
With these data, it’s possible to start to imagine what the use of a Grail cancer blood test would look like in the real world. Dr. Anne-Renee Hartman, Grail’s vice president of clinical development, said that between 1% and 1.5% of people older than 50 develop cancer each year. So a test that looked at 100,000 individuals and detected cancer in 70% of them would find 700 cancers. If it had a 99% specificity, it would tell 1,000 people who do not have cancer that they had the disease. The test would tell doctors where to look, and they would have to calm those whose tumors could not be found and treat those whose tumors were findable.
This may not sound great. The test would still be scaring more people unnecessarily than it’s helping. But Hartman and Aravanis pointed out that that’s far better than existing tests like mammography, CT screening, or PSA. Those, Aravanis said, have false positive rates that are 10 times higher.
Still, while the Grail executives said they envision the company’s test used to screen large numbers of people, they also pointed out that their big studies contain plenty of people at higher risk, like heavy smokers or people with mutations known to increase their risk of cancer. Anirban Maitra, a pancreatic cancer researcher at MD Anderson Cancer Center, said that if you look just at pancreatic cancer, not all cancers, it’s likely almost 1,000 people who don’t have cancer would be identified for every 15 that are diagnosed. “It may be better to apply tests of this nature in a pre-selected high risk population (mutation carriers, or cohorts being followed for cancer surveillance due to some concurrent high risk features) before going all in on a general population,” he said.
Dr. Charu Aggarwal, an assistant professor of medicine at the University of Pennsylvania, said she, too, would like to see the test tried in patients at higher risk. But she also was surprised and impressed by the data. “I’m really intrigued,” she said.
Aravanis also argued that Grail has another advantage here: that it appears to be detecting deadlier early-stage tumors, no matter where they are in the body. “All cancers are not the same. We really want to find those cancers that are dangerous that grow, progress and cause clinical harm,” he said.
Grail is taking the next steps. Hartman, its head of clinical development, said that the company plans to soon start experiments where it will return results back to patients and their doctors, so they can understand what patients do with the information. Until now, Grail has been taking patients’ blood and watching, but not telling them about the results of its still-experimental tests.
Dr. Otis Brawley, a professor of oncology and epidemiology at Johns Hopkins University, said he was impressed by the data.
“This is truly exciting in that it’s a company that has consistently tried to do the right thing in developing a screening test,” he said. “Many companies have tried to cut corners.”
Aravanis also said that the company is cognizant that its final test can’t be too expensive, and that it is targeting small enough areas of the genome that it can make the test affordable. “We want this to be broadly accessible when deployed,” he said. “Being able to price it in a way that’s compatible with that is very important to us.” He gave a range from $600 to a few thousand dollars, and said that it would get to the low end of that range if possible.
There will definitely be competition. Yesterday, Thrive, a Cambridge., Mass.-based company, announced that it had raised $110 million to develop a competing test developed by researchers at Johns Hopkins University. That test combines DNA and protein data to tell where in the body tumors are. Thrive says its test will cost hundreds of dollars. The race is on.

Men using active surveillance in prostate cancer often don’t monitor correctly

Preliminary results from a University of North Carolina Lineberger Comprehensive Cancer Center study found that just 15 percent of a group of men in North Carolina with early-stage prostate cancer who choose active surveillance instead of treatment followed the recommended monitoring guidelines.
The findings, to be presented Sunday, June 2, at the American Society of Clinical Oncology Annual Meeting 2019 in Chicago, were drawn from an analysis of 346 men newly diagnosed between 2011 and 2013 with low or intermediate-risk prostate cancer in North Carolina. Researchers analyzed how often men received biopsies and other tests according to the guidelines from the National Comprehensive Cancer Network.
“Active surveillance has rigorous guidelines — people need regular PSA tests, they need prostate exams, they need prostate biopsies so you can watch the cancer very closely, and you don’t lose the opportunity to treat the cancer when it starts to grow,” said UNC Lineberger’s Ronald C. Chen, MD, MPH, associate professor in the UNC School of Medicine Department of Radiation Oncology. “One of the main findings of this study is that in this population-based cohort, not in a clinical trial or purely academic setting, only 15 percent of patients in active surveillance received recommended monitoring.”
Data have shown that active surveillance is safe, but UNC Lineberger researchers note that those data have been drawn from clinical trials or studies in large academic institutions. To evaluate monitoring in a broad population, they studied a group of patients from North Carolina to determine if they adhered to NCCN active surveillance guidelines, which recommended prostate-specific antigen (PSA) tests at least every six months, digital rectal exams annually, and a repeat biopsy within 18 months of diagnosis.
In the first six months, 67 percent of patients had received a PSA test, and 70 percent received a digital rectal exam. Just 35 percent received a biopsy within the first 18 months. Across all types of tests by 24 months, only 15 percent of patients received monitoring compliant with the guidelines.
“Based off of the NCCN guidelines, which is what we believe most of the community practices would be following in terms of active surveillance guidelines, we’re finding very few patients who elected to undergo active surveillance actually received the recommended monitoring,” said the study’s first author Sabrina Peterson, a student at the UNC School of Medicine.
Researchers also reported they did not find any variables, such as income, race or age, linked with whether or not patients would adhere to the monitoring guidelines. The findings led researchers to call for more research into outcomes for active surveillance outside of controlled studies.
“This raises the question of whether we need to investigate whether active surveillance is a safe option when patients do not receive routine monitoring,” Chen said. “Our goal is not to reduce the number of patients choosing active surveillance; rather, the results of this study should increase awareness and efforts to ensure that active surveillance patients are monitored rigorously.”
Researchers also analyzed trends linked to patients who stopped active surveillance and started treatment. In addition to finding that disease progression motivated patients to switch to treatment, they found that a patient’s level of anxiety was linked to whether or not they stopped active surveillance and switched to treatment.
“When we looked at some of the reasons why people would have treatment instead of active surveillance, anxiety seems to be one of the reasons why people have treatment and stop active surveillance,” Chen said.
In addition to Chen, other authors included Sabrina Peterson, Ramsankar Basak, Dominic Himchan Moon, Claire Liang, Deborah S. Usinger, Sarah Walden, and Aaron J. Katz.
The study was supported by the Patient-Centered Outcomes Research Institute and the Agency for Healthcare Research and Quality.

Fast moving Chinese regulators wave third homegrown PD-1 to market

Jiangsu Hengrui has secured an OK for its PD-1 drug, marking the fifth PD-1 approval in China and tilting the scale toward homegrown checkpoints.
Hengrui — a top 25 biopharma company globally led by Piaoyang Sun — joins Junshi and Innovent in facing foreign counterparts: Merck’s Keytruda and Bristol Myers’ Squibb’s Opdivo.
Its drug, camrelizumab, has long been tapped as one of the first finishers in China’s heated checkpoint race. Incyte dished out $25 million plus $770 million in biobucks to partner on its PD-1, although an odd adverse reaction diminished the American biotech’s enthusiasm.
Regardless, the National Medical Products Administration sanctioned camrelizumab as a treatment for recurrent or refractory classical Hodgkin’s lymphoma following two lines of systemic chemotherapy.
That’s the exact indication that Innovent scored for its drug Tyvyt, which goes to show how quickly indications can get crowded.
Meanwhile, Junshi’s Tuoyi is indicated for melanoma, as is Keytruda — though Merck recently racked up an additional approval in non-small cell lung cancer.
All told, these drugs totaled $6.4 million in sales in 2018, according to IMS data quoted by Hengrui.
BeiGene, CStone and Alphamab are among the more well-known players also angling for near-term approval of their own checkpoints, with Hodgkin’s lymphoma set to be a key battleground.
Hengrui, though, is also exploring NSCLC, esophageal cancer and hepatocellular cancer in Phase III while also eyeing a green light in the US.

eHealth: Medicare Advantage premiums drop 33% during latest enrollment period

Medicare Advantage (MA) and Part D applications were up 87% during the open enrollment period between January and March compared to the same period last year, according to a new report from eHealth.
The report looks at the costs and reactions from enrollees of Medicare’s latest open enrollment period. During the first three months of this year, the average MA premium dropped 33% from $12 to $8 from 2018, and average out-of-pocket limits decreased 11%. The average monthly premium for Part D coverage decreased during this time as well from $26 to $25.
Chris Hakim, senior vice president and general manager of Medicare for eHealth, said the company has been tracking the downward trend on average MA premiums for some time. It was noted in eHealth’s previous report at the year-end annual enrollment period as well.
“This may be a sign of strong competition and increased efficiency in the Medicare Advantage market,” Hakim told FierceHealthcare.
More than half of respondents (53%) used open enrollment as an opportunity to switch from one MA plan with prescription drug coverage to another plan also with drug coverage.
During the time period, average deductibles for MA plans with prescription drug coverage decreased from $151 to $132, but deductibles for Part D plans increased from $292 to $308.
Currently, a person enrolled in an MA plan can leave the plan and return to original Medicare or join another Advantage plan during open enrollment. Prior to 2018, enrollees could not switch to a different MA plan during those months. Now that midyear options for enrollment are available, Hakim notes that there are several factors that might lead to more plan swapping among MA enrollees.
For example, Hakim notes that a lot of baby boomers are aging into Medicare, and this group is tech-savvy, careful with money and increasingly comfortable comparing options and enrolling online.
“The combination of more Medicare Advantage plans coming into the market and increased competition, increased transparency in cost and coverage, plus a more informed and tech-savvy buyer, there’s plenty of reason to think this is a trend that will continue,” he said.
Still, half of the respondents of this study had not previously been aware of the new open enrollment period before reviewing coverage options, and 38% learned about it only after contacting an agent or broker. In addition, 31% learned about it from a news source.

Hakim was surprised that half of the respondents who bought new coverage had visited first but didn’t enroll there, and those that bought from eHealth instead noted they wanted help from a licensed agent. So how did consumers react to this year’s open enrollment period?
Respondents changed plans due to dissatisfaction with old insurers (22%), dissatisfaction with copays (15%) or because a preferred doctor was no longer in-network (12%).
“I think our report, combined with regulatory changes and encouragement from the federal government, suggests we’ll continue to see an expansion of Medicare Advantage plans in the market and increased enrollment by Medicare beneficiaries,” Hakim added. “With increased competition, we may continue to see decreasing average premiums. A big factor in those decreasing premiums is the popularity of $0 premium Medicare Advantage plans.
“While Medicare Advantage plans may not be the best match for everyone in every situation (some people prefer original Medicare with a Medicare Supplement plan), they work for a lot of people, and it’s no mystery why they’re so attractive,” he said.

Turning Point makes push to outdo Pfizer, Roche in targeted cancer therapy

  • Turning Point Therapeutics, a San Diego-based biotech six weeks from its public market debut, unveiled fresh clinical results Friday that keep it on track to challenge Pfizer, Roche, and Eli Lilly in the fast-moving field of targeted cancer therapies.
  • Expanded data from an early Phase 1/2 trial showed treatment with repotrectinib, Turning Point’s experimental tyrosine kinase inhibitor, caused tumors to shrink in nine of 11 lung cancer patients never treated with similar drugs, and seven of 22 previously treated.
  • That latter group of patients is particularly important for the biotech. Drugs like Pfizer’s Xalkori are commonly used as initial treatment for people diagnosed with a type of non-small lung cancer driven by a mutation known as ROS1. Treatment resistance can develop for some, however, after which options are limited.

Turning Point raised nearly $200 million from an initial public offering last month, capitalizing on widespread enthusiasm for targeted cancer therapies.
Founded in 2013, the biotech aims to replicate the success of companies like Loxo Oncology and Ignyta, the targets of recent buyouts by Eli Lilly and Roche, respectively.
Both Loxo and Ignyta drew attention with drugs designed to home in on tumors spurred to grow by rare genetic mutations, posting encouraging data that lured their eventual pharma buyers. In the case of Loxo, positive results for patients with solid tumors harboring abnormal fusions of a gene called NTRK to other strips of DNA led to the approval of Vitrakvi (larotrectinib). Bayer acquired rights to Vitrakvi before Lilly’s acquisition.
Turning Point believes it can outdo its targeted cancer peers with repotrectinib, which it’s developing for NTRK positive as well as ROS1 positive cancers.
Friday’s data, which will be presented at the annual meeting of the American Society of Clinical Oncology, is the first look at repotrectinib that new investors in Turning Point have had since October.
Results among patients never treated with tyrosine kinase inhibitors, or TKIs, are from just 11 patients. But the response rates to repotrectinib appear on par at this early stage with those for Xalkori (crizotinib) and entrectinib in ROS1 positive lung cancer.
Notably, repotrectinib also looks active in individuals already treated with TKIs. A 2017 study of lung cancer patients given Xalkori found more than half of tumor specimens studied had developed resistance, mutating in response to treatment.
One type of genetic alteration, known as solvent front mutations, are particularly problematic for most of the TKIs approved or in development due to the way the drugs bind to the targeted kinase. According to Turning Point, repotrectinib’s design allows the drug to sidestep this type of resistance mutation, potentially making the drug a better candidate for patients who no longer respond to Xalkori or similar therapies.
The company’s claim is bolstered by having J. Jean Cui as founder and chief scientific officer. Cui worked for Pfizer from 2003 to 2013 and is described in Turning Point’s prospectus as an inventor for Xalkori and the pharma’s more recently approved lung cancer drug Lorbrena (lorlatinib).
Results presented Friday showed 32% of TKI-pretreated patients responded to repotrectinib, a rate that rose to 55% when only counting those patients who received what Turning Point sees as its therapeutic dose. In five study participants who tested positive for one of the more common resistance mutations, two experienced confirmed partial responses.
It’s worth noting, however, that none of the four patients previously treated with two or more TKIs responded.
Athena Countouriotis, Turning Point’s CEO, said the data give her confidence repotrectinib can stand out from its rivals.
“Patients will get tested and if they have solvent front mutations, I don’t believe physicians will give anything else other than repotrectinib,” Countouriotis said in an interview with BioPharma Dive.
Investors, however, didn’t appear as convinced. Shares in Turning Point fell by more than 15% Friday morning, bringing the company’s market value close to dropping below $1 billion.
Turning Point plans to start the Phase 2 portion of its study later this year, with plans to enroll up to 190 patients with ROS1 positive non-small cell lung cancer. Patients will be divided into three cohorts: those TKI-naive, those pretreated with 1 prior ROS1 TKI and those with 2 previous lines of ROS1 TKI therapy.
While repotrectinib’s activity in pretreated patients may give it a competitive edge, Countouriotis says the company’s plan is to go after both patient populations.
“The Phase 2 design accommodates multiple paths to approval,” she said.
The Food and Drug Administration has proved willing to consider accelerated approval for targeted drugs that show clear activity against genetically defined cancer types — although some are now wondering whether the bar has been set too low.
Vitrakvi, for example, was conditionally approved on strong response rate data from 55 patients. Turning Point could feasibly pursue a similar route to market.
Even if repotrectinib is approved, though, Turning Point will compete with much larger rivals. Pfizer earned more than $500 million from sales of Xalkori last year and is studying Lorbrena in ROS1 positive tumors. Roche expects a decision from the FDA on entrectinib by August and Lilly is advancing a successor to Vitrakvi in TRK positive cancer, another target of Turning Point’s.
Such powerful competitors are notable given the small number of patients involved. Turning Point estimates between 2% and 3% of patients with advanced non-small cell cancer have tumors positive for ROS1. Estimates by the investment bank Leerink put the second-line population at 1,900.
Investors may see an opportunity for Turning Point to be acquired as Loxo and Ignyta were before it.  For now, though, Turning Point thinks it can take on the challenge solo. “Our intention is to take repotrectinib all the way,” said Countouriotis.

Heritage charged in fed generic price fixing case

Heritage Pharmaceuticals Inc., a generic pharmaceutical company headquartered in Eatontown, New Jersey, was charged for conspiring with its competitors to fix prices, rig bids, and allocate customers, the Department of Justice announced today.
According to a one-count felony charge filed yesterday in the United States District Court for the Eastern District of Pennsylvania in Philadelphia, from about April 2014 until at least December 2015, Heritage participated in a criminal antitrust conspiracy with other companies and individuals engaged in the production and sale of generic pharmaceuticals, a purpose of which was to fix prices, rig bids, and allocate customers for glyburide, a medicine used to treat diabetes.  This charge is the third in the Department of Justice’s Antitrust Division’s ongoing investigation; Heritage’s former CEO and its former president were previously charged.
The Antitrust Division also announced a deferred prosecution agreement resolving the charge, under which Heritage admits that it conspired to fix prices, rig bids, and allocate customers for glyburide.  Under the agreement’s terms, Heritage will pay a $225,000 criminal penalty and cooperate fully with the ongoing criminal investigation.  The United States will defer prosecuting Heritage for a period of three years to allow the company to comply with the agreement’s terms.  The agreement will not be final until accepted by the court.
The Antitrust Division entered into the deferred prosecution agreement with Heritage based on the individual facts and circumstances of this case.  Among those facts and circumstances, the agreement specifically identifies the company’s substantial and ongoing cooperation with the investigation to date, including its disclosure of information regarding criminal antitrust violations involving drugs other than those identified in the criminal charge and the agreement.  According to the agreement, this cooperation has allowed the United States to advance its investigation into criminal antitrust conspiracies among other manufacturers of generic pharmaceuticals.  Other facts and circumstances identified in the agreement include: Heritage has agreed to resolve all civil claims relating to federal health care programs arising from its conduct; and a conviction (including a guilty plea) would likely result in the Office of the Inspector General of the Department of Health and Human Services imposing mandatory exclusion of Heritage from all federal health care programs under 42 U.S.C. § 1320a-7 for a period of at least five years, which would result in substantial consequences, including to American consumers.  The agreement can ensure that integrity has been restored to Heritage’s operations and preserve its financial viability while preserving the United States’ ability to prosecute it should material breaches occur.
In a separate civil resolution, Heritage has agreed to pay $7.1 million to resolve allegations under the False Claims Act related to the price-fixing conspiracy.  The government alleged that between 2012 and 2015, Heritage paid and received remuneration through arrangements on price, supply, and allocation of customers with other pharmaceutical manufacturers for certain generic drugs in violation of the Anti-Kickback Statute, and that its sale of such drugs resulted in claims submitted to or purchases by federal healthcare programs.  The drugs allegedly implicated in this scheme address a wide variety of health conditions, and include hydralazine, used to treat high blood pressure, theophylline, used to treat asthma and other respiratory problems, and glyburide.

China's Fosun Slows Down Investment in U.S. Biotech Sector Due to Trade Issues

Continued Sino-American trade relation concerns are forcing one company to rethink its investment opportunities in the United States.
Kevin Xie, a spokesperson for China-based Fosun International, told Bloomberg that the conglomerate plans to limit its investments in U.S.-based biotech companies to “small stakes.” The cautious investment plan is a response to the increased scrutiny of Chinese investments in U.S. pharma and biotech by the federal government. Washington has been increasingly focused on Chinese investment in the United States, particularly in the areas involving intellectual property and biotech. Earlier this year, Congress almost unanimously passed an updated version of the review powers of the Committee on Foreign Investment in the United States. That review power though has raised concerns in companies like Fosun, particularly after the White House ordered the Chinese majority owner of Massachusetts-based healthcare company PatientsLikeMe to sell his stake, as well as the more recent issues with Chinese tech company Huawei Technologies.
“Trade friction has impacted our investments in the U.S., but not to the extent of stopping all deals," Xie told Bloomberg. “Companies in the U.S. still welcome investments and are willing to work with us, so we are making some changes in the wiggle room allowed under the law.”

As Bloomberg notes, Chinese investment in the U.S. pharmaceutical industry has been significant in recent years. Last year, China invested $2.8 billion in U.S. health care companies, a big jump from the $702.9 million in 2017, Bloomberg said. Some of the deals from 2018 include a team-up between BeiGene and SpringWorks Therapeutics to develop therapeutics that will target advanced solid tumors that contain RAS mutations, as well as other MAPK aberrations. Also last year, WuXi’s subsidiary Shanghai SynTheAll Pharmaceutical Co., Ltd., a contract development and manufacturing organization, secured a physical toehold in the United States, opening an operation site in San Diego that will provide process research and development as well as API manufacturing services for early phase clinical studies. WuXi also previously formed a partnership with Seattle-based Juno Therapeutics to develop treatments for cancer with the formation of a new Chinese company called JW Biotechnology Co., LtdThe new Chinese company’s mission will be to build a cell therapy company in China.
China’s increased focus on investing in health care and becoming a global leader in the field has become a concern for Washington, particularly related to issues of intellectual property and patient data. Typically, the power of CFIUS has come into play when deals are involving billions of dollars, but as more Chinese money flows into the U.S. sector, the government is using the program more and more to scrutinize even the smallest of deals.

A 2017 report issued by the FBI noted that that intellectual-property theft by China costs the U.S. as much as $600 billion annually. Last year, two Chinese scientists pled guilty to stealing intellectual property from GlaxoSmithKline. Those trade secrets were going to be part of the foundation for setting up a company in China called Renopharma. Even researchers at vaunted colleges and cancer centers have come under scrutiny over funding from China or concerns of espionage. Emory University terminated some employees over funding from China the college said was not disclosed, while MD Anderson dismissed three ethnically Chinese scientistswho have been associated with espionage conducted by the government of China following an investigation conducted by the National Institutes of Health.

J&J: Will appeal $300 million punitive damages ordered in NY talc suit

Johnson & Johnson was ordered Friday to pay $300 million in punitive damages to a woman who blamed her rare asbestos-related cancer on the company’s talc-based products, the company confirmed Friday.
Friday’s decision brings the total award in the case to $325 million. The New York state jury earlier this month awarded $25 million to the woman, Donna Olson, 66, and her husband in compensatory damages.
“With this verdict, yet another jury has rejected J&J’s misleading claims that its talc was free of asbestos,” said Jerome Block, the lead trial attorney in the New York case. “The internal J&J documents that the jury saw, once more laid bare the shocking truth of decades of cover-up, deception and concealment by J&J of the asbestos found in talc baby powder.”
J&J faces more than 13,000 talc-related lawsuits. The consumer products company, which makes everything from Tylenol to Aveeno lotions, denies allegations that its talc causes cancer. It said numerous studies and tests by regulators worldwide have shown that its talc is safe and asbestos-free.
“This trial suffered significant legal and evidentiary errors which Johnson & Johnson believes will warrant a reversal on appeal,” J&J said in a statement to CNBC. “Decades of tests by independent experts and academic institutions repeatedly confirm that Johnson’s Baby Powder does not contain asbestos or cause cancer.”
J&J relaunched its iconic namesake baby product line last summer to reverse a decline in J&J’s baby care unit. While trusted for decades, the 124-year-old brand had fallen out of touch with consumers, namely millennial moms, who opted instead for cleaner, natural products from trendy upstart brands.

So-Young target raised at Canaccord

To $21 from $20; maintains Buy.

Reata Pharmaceuticals target hiked by Citi

To $190 from $185; maintains Buy.

Ascendis Pharma target raised by Canaccord

To $144 from $133; maintains Buy.

Acadia Pharmaceuticals target hiked by Raymond James

To $43 from $40, maintaining Strong Buy.

Novartis: Sandoz launches 1st generic of big AstraZeneca breast cancer med

Sandoz today announced that the first generic Fulvestrant Injection has been approved by the US Food and Drug Administration (FDA) and is immediately available in the US.
It is a fully substitutable AP rated generic version of AstraZeneca’s FASLODEX (fulvestrant) Injection.
This hormonal therapy medicine is recommended for the three quarters of women with advanced breast cancer whose tumor expresses the estrogen receptor (ER), and slows tumor growth by binding to and blocking the ER, a key driver of disease progression1.
‘Fulvestrant is an important treatment option for women with advanced breast cancer and we will work to help those in the US who need this critical therapy have access to it at an affordable price,’ said Carol Lynch, President of Sandoz Inc. ‘This treatment fits well with our ongoing strategic focus on oncology, where Sandoz has substantial experience bringing important oncology medicines to hospitals, clinics, doctor’s offices and patients in the US.’
According to IQVIA, US sales for FASLODEX (fulvestrant injection) for the 12-month period ending March 2019 were USD 541 million (MAT: Moving Annual Total).

Celgene partner BeiGene plots post-merger course

Now that the $74 billion acquisition of Celgene by Bristol-Myers Squibb is more or less a done deal, one question remains for BeiGene: What does it plan to do with its Celgene-partnered checkpoint inhibitor, tislelizumab?
The short answer? If—or, most likely, when—BeiGene does end up flying solo with the PD-1 immunotherapy, the impact on clinical development would be “marginal,” and the financial hit would be “modest,” BeiGene Chief Adviser Eric Hedrick, M.D., told FiercePharma in an interview.
The concern isn’t so much about BeiGene’s path forward for tislelizumab in China, where it’s under priority review for classical Hodgkin lymphoma (cHL), but rather in the U.S., EU and Japan in solid tumors. Those are the areas where Celgene currently holds tiselelizumab rights.
“In the contract, there’s stipulation that they basically can’t hold two PD-1-class assets,” Hedrick said of BeiGene’s pact with Celgene. That means, once the merger closes as expected in the third quarter, there’s no reason for Opdivo seller BMS to hang onto tislelizumab. “We fully expect that the rights to our PD-1 inhibitor globally will be transferred back to us,” he said.
BeiGene made its name back in the summer of 2017 when it penned that unusual deal with Celgene. Under the agreement, Celgene made a $150 million investment in BeiGene and transferred its Chinese commercial operations, including rights to marketed drugs like Revlimid, to the Chinese biotech.
The BMS-Celgene merger will have “zero” effect on that part of the deal, Hedrick said. And the second part saw Celgene shell out $263 million upfront for tislelizumab rights.
At the time, BeiGene was just a small company. “One of the appealing aspects of doing this deal was for us to bolster our capability to develop that drug on a global basis,” Hedrick explained.
That has changed dramatically over the past two years, he said, and BeiGene’s in a good position now to run the show. Its ability to conduct clinical development globally has “increased exponentially,” he added.
Today, BeiGene’s clinical development team is more than 800 strong, with about half of those employees located outside of China. And that team is handling more than 50 ongoing or planned clinical studies as of January, the company said in its recent annual securities filing.

For tislelizumab specifically, 90% of the registrational trials are already in BeiGene’s hands, so “the operational impact for us is negligible,” Hedrick said, adding that the company doesn’t expect any major hiring or organizational changes. The only major study conducted by Celgene is testing tislelizumab alongside chemo and radiation as a post-surgery treatment for locally advanced non-small cell lung cancer.
“The financial aspects of us getting rights back would be mitigated by the fact that all the trials that we’re getting reimbursed by Celgene will complete accrual by the end of the year,” he said.
That said, development is only part of the picture, and merely pushing the drug to approval doesn’t necessarily translate into commercial success. Without help from an oncology bigwig, marketing neophyte BeiGene might have a tough time launching, especially in the U.S. where Merck & Co.’s Keytruda, BMS’ Opdivo and Roche’s Tecentriq have secured footholds in many major indications.
BeiGene could take a page from Sanofi and Regeneron, though. The pair first went after a small niche market with their sixth-to-market Libatyo.
“If you look at the first wave of registrational trials, a lot of those are in the cancer types that are prevalent in Asia,” Hedrick said. Lung cancer is of course part of that cohort, as it’s the most common cancer type in China as well as in the U.S. But many studies are in gastrointestinal-related malignancies, such as liver, stomach and esophageal cancers, that are also common on the continent.

“The China part of that commercialization is going to be a major focus,” Hedrick said. “That’s how we think we can be competitive.”
By focusing on Asia-prevalent cancers, BeiGene could stake a claim in Asia and other parts of the world. Just consider gastric cancer, where Keytruda has failed phase 3 studies in both newly diagnosed and previously treated patients.
For now, BeiGene is building its global commercialization presence “step-wise,” Hedrick said. It has brought in a senior team to handle U.S. sales and marketing for its BTK inhibitor zanubrutinib, for instance, which recently became the first China-developed drug to win an FDA breakthrough designation.
The first U.S. filing for that drug, in Waldenström’s macroglobulinemia, will happen in the first half of next year, and it will be another year before it’s tislelizumab’s turn, according to Hedrick.
While in the long term BeiGene aims to be a global commercialization force in its own right, in the near term for tislelizumab, it might scout for new partners if the BMS-Celgene transaction goes through as planned, Hedrick said.
The Chinese approval is more imminent: It’s expected later this year. Five PD-1s are already approved in China, including Keytruda, Opdivo and three local rivals. Jiangsu Hengrui Medicine’s camrelizumab just won a nod in Hodgkin lymphoma—the same initial indication tislelizumab is after. For China, BeiGene’s plan is to run a broad development program and get “as many approved indications as possible listed for national reimbursement,” he said.
Compared to what Merck executives has touted as Keytruda’s “wall of data,” the data tislelizumab has yielded so far are quite thin. They’re mostly phase 2 results in small trial groups and only comprise overall response stats.
But BeiGene plans to build a wall of data of its own, and it has a good start. In its single-arm China phase 2 trial in 70 patients with relapsed/refractory cHL, tislelizumab achieved a complete response rate of 61%, about two times that of other PD-1 inhibitors, Hedrick touted.