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Tuesday, June 5, 2018

#ASCO18: AbbVie convinces analyst $6B ‘megablockbuster’ Rova-T is worthless



AbbVie $ABBV has managed to convince at least one prominent analyst that Rova-T is absolutely worthless, as the company’s vision of a $5 billion earner gradually dissolves.

Geoffrey Porges at Leerink took a look at AbbVie’s formal presentation of its Trinity trial data at ASCO and came away shaking his head. His conclusion:
The results shown in the presentation were even worse than we had feared, and although AbbVie’s stock sold off much more than the value of Rova- T after the announcement, we can’t help but regard the ongoing trials as largely fruitless exercises. Furthermore, the toxicity signal from the trial, along with the relatively marginal efficacy signal, justifies the complete elimination of all revenue associated with Rova-T from our company forecast and valuation for AbbVie.
There was a lot to dislike about the data, he says, including the high 34% discontinuation rate in the study; “49 or these 116 premature discontinuations were due to progressive disease, with the others being due to adverse events or other undisclosed reasons.”
For the primary endpoint over response rate, measured by change in the target lesion, of the 301 evaluable patients (presumably the other 38 patients were deceased or lost to follow up), the investigator-measured response rate was 18%, increasing modestly to 19.7% in the DLL3 high group.
As measured by the independent review board,  the response rate fell to 12.4% for the combined population, and 14.3% in the DLL3-high patients. And serious adverse events in the drug group ran high.
AbbVie paid $5.8 billion in cash for this drug, promising up to $4 billion more in milestones to acquire the little-known biotech unicorn Stemcentrx. And with money like that on the table, expectations were running high, fueling forecasts that the pharma company could get past the eventual loss of patent protection on Humira in style. AbbVie itself projected peak sales at $5 billion a year.
Porges’ conclusion: The drug and the class look dead on arrival at ASCO.
Ultimately it seems unlikely in our view that Rova-T, or perhaps any variant of DLL3 antibody-drug conjugate medicine, will come to market, at least while the profile looks the way it did in TRINITY.

‘Millions’ prescribed wrong dose of common drugs


According to updated calculations published this week, over 11 million people in the United States may have been given the wrong prescription for a range of commonly used drugs.
Scientists from the Stanford University School of Medicine in California recently investigated the reliability of so-called pooled cohort equations (PCEs).
These dry-sounding sums perform a pivotal role in the prescribing of drugs, including blood pressure medications, statins, and aspirin.
PCEs help doctors to determine each patient’s overall risk of stroke or heart attack.
Assessing cardiovascular risk helps to inform the physician about the exact level of medication that will be both effective and safe.
These equations are available as online web tools and smartphone apps, and they are even built into digital medical records.

Problems with PCEs

In recent years, some have called into question the accuracy of PCEs, asking whether the data that they rely on are outdated. If this were found to be the case, patients could potentially be at risk of taking dangerously high or ineffectively low doses of drugs.
Dr. Sanjay Basu, Ph.D., is an assistant professor of primary care outcomes research at Stanford. He set out to uncover whether PCEs should be improved. As he explains, “We found that there are probably at least two major ways to improve the 2013 equations.”
His findings were published this week in the journal Annals of Internal Medicine.
The first issue that Dr. Basu identified was one that had been discussed for some time: “[T]he data used to derive the equations could be updated.”
PCEs are based on various datasets, some of which are relatively old. For instance, one included information from people who were aged 30–62 in 1948.
Diet, lifestyle, health risks, and everything in-between have changed since those days. The study authors say that, because of the age of this information, people’s risks were being estimated at around 20 percent higher than they truly were.
Dr. Basu notes dryly that “relying on our grandparents’ data to make our treatment choices is probably not the best idea.”

Other issues unearthed

Another issue the researchers identified was the lack of African-Americans in the datasets. It is now known that cardiovascular risk is significantly higher in the African-American population.
So while many Americans were being recommended aggressive treatments that they may not have needed according to current guidelines, some Americans — particularly African-Americans — may have been given false reassurance and probably need to start treatment given our findings.”
Dr. Sanjay Basu, Ph.D.
To rectify these shortcomings, the researchers added new data to improve the PCEs’ accuracy. The data are currently maintained by the National Institutes of Health (NIH), and they have approved the new and updated equations.
Addressing the aged data was the first step, but there was a second issue to attend to. According to the researchers, some of the statistical methods behind the PCEs were also outdated. So, they brought them in line with current standards.
In the paper, the study authors explain, “We found that by revising the PCEs with new data and statistical methods, we could substantially improve the accuracy of cardiovascular disease risk estimates.”
As the PCEs guide medical decisions involving some of the most commonly used prescription drugs — such as aspirins, blood pressure medications, and statins — these changes could potentially save and extend thousands of lives.

NYU Langone to open new high-rise hospital with superstorm protection

When Hurricane Sandy caused destructive flooding along the East Coast in 2012, the New York University Langone Medical Center campus sustained significant damage.
Power was cut, health providers were forced to evacuate more than 300 patients, and officials had to not only renovate and weatherproof existing buildings but ensure their planned campus construction wouldn’t allow the campus to be impacted by flooding that way ever again.
The Kimmel Pavilion (NYU Langone)
Now, as NYU Langone prepares to open the 21-story Helen L. and Martin S. Kimmel Pavilion on the east side of Manhattan later this month, officials said they are not only marking the delivery of the final step of a long-planned upgrade to health services in the city: They have finished the final piece of the effort to protect against future superstorms.
“It completes that perimeter wall for us to protect that entire campus,” Vicki Match Suna, NYU Langone’s senior vice president and vice dean for real estate development and facilities, told FierceHealthcare.
The Kimmel Pavilion was the final phase of $6 billion campus plan, which included the creation of a new energy facility and science research building. Those projects were already well underway but needed a revamp after Sandy hit, Match Suna said. “We quickly had to reassess our campus plan in terms of resiliency for the future and very rapidly made a lot of changes to the design,” she said.

That involved changing plans such as moving much of the mechanical and electrical infrastructure up to the first floor, she said. A new protection wall that protects the campus from one end to the other has gates at every necessary break in the perimeter that can be shut when any kind of surge from the river is expected.
It’s one of the unique design features of the new 830,000-square-foot Kimmel Pavilion project, the largest and most extensive revitalization in NYU Langone Health’s history. The building officially opens June 24.
An operating room in the new building.
(NYU Langone)
Among its other features, the building includes 374 private inpatient rooms as well as outdoor landscaped gardens and roof terraces with views of the city.
The new Hassenfeld Children’s Hospital with two floors will be dedicated to 68 inpatient pediatric beds, When it opens, it will be the only pediatric inpatient facility in Manhattan with all private patient rooms, officials said. The 160,000-square-foot children’s hospital has its own designated building entrance on 34th Street and will include a pediatric intensive care unit, congenital cardiovascular unit, surgery services and a pediatric emergency department.
The pavilion will greatly increase the health system’s capacity for procedure-based volumes with 30 new operating rooms and image-guided labs, as well as acute care and critical care services in hematology/oncology, bone marrow and solid organ transplantation, Match Suna said. The health system’s bed count has not increased significantly because the new building is helping create private patient rooms while officials plan to renovate the existing NYU Langone Tisch Hospital, she said.
In January, NYU opened its 16-floor science building, which includes more than 365,000 square feet and 10 floors of laboratory space covering medical research such as neuroscience, the Institute for System Genetics, Institute for Computational Medicine, cardiology, endocrinology and rheumatology.
The Energy Building, which opened in May 2016, allows the campus to be more environmentally sustainable but also allows the health system to power its buildings and remain operational in the event of a utility power interruption, with two different sources of backup power for critical areas.

VBL Therapeutics gains after CEO comments on series of antibodies


In a statement, CEO of VBL Therapeutics, Dror Harats, M.D, said, “Our research has shown that MOSPD2 plays a key role in the regulation of cell motility.We have generated data indicating that MOSPD2 is required for directional movement, or chemotaxis, of tumor cells and certain immune cells, and therefore appears to play a central role in both oncology and inflammation. We continue to advance our exciting VB-600 series of antibodies as drug candidates for oncology and inflammatory indications.” Shares of VBL Therapeutics are up about 47% to $3.20 per share in after-hours trading.

Exact Sciences, Mayo ID liver cancer biomarker


Researchers at Exact Sciences Corp. (Nasdaq: EXAS) and Mayo Clinic announced significant progress toward developing a panel of novel, blood-based, DNA biomarkers that could accurately detect hepatocellular carcinoma (HCC), the most common cancer that originates in the liver.1 The researchers detailed their findings during a presentation today at Digestive Disease Week, the world’s largest gathering of gastroenterologists and scientists in the field.
The biomarker panel was shown to be 95 percent sensitive for detecting HCC across all stages. Sensitivity among patients with curable-stage disease was 91 percent. The panel has overall specificity of 93 percent, demonstrating its ability to discriminate between normal and diseased patients. Sensitivity and specificity are the most important statistical measures of a cancer detection test’s performance.
“These results are further validation of our advanced DNA technology and our multi-biomarker approach for the detection of the deadliest forms of cancer,” said Kevin Conroy, chairman and CEO of Exact Sciences. “We look forward to advancing this important research in early stage cancer with Mayo Clinic.”
HCC accounts for nearly 90 percent of all liver cancers and is the fastest-growing cause of cancer-related death in the United States.1 Mayo Clinic experts predict that liver and bile duct cancers will be the third-leading cause of cancer deaths in the United States by 2030 due, in part, to the obesity epidemic.2,3
Individuals diagnosed with cirrhosis have the greatest risk of developing HCC, and it is recommended that they undergo ultrasound and blood monitoring every six to 12 months. The three-year survival rate for patients regularly surveilled is approximately 60 percent, compared to approximately 30 percent for those who don’t undergo regular surveillance.4 When HCC is detected early and treated, patient survival rates improve significantly.1 Exact Sciences estimates that more than 3 million Americans are eligible for HCC surveillance.
“The potential of an accurate, non-invasive blood test that can identify early-stage disease is very exciting,” said John Kisiel, M.D., the gastroenterologist and assistant professor of medicine at Mayo Clinic Medical School who led the study. “This could potentially transform the way patients are monitored and lead to the identification of many more curable-stage tumors than we typically see today.”
Dr. Kisiel said the current options for monitoring at-risk patients are “sub-optimal.”
“We estimate that fewer than half of at-risk patients are tested regularly, and some estimates suggest the monitoring rate is less than 20 percent in primary care settings, where most people get their care,” Dr. Kisiel said.
Using DNA extracted from the blood samples of 244 people, including 95 diagnosed across all stages of HCC, 51 with cirrhosis, and 98 healthy volunteers, researchers tested the samples against 15 biomarkers to identify the combination of six biomarkers that yielded the most accurate detection of HCC.
“Now we must confirm the accuracy of the biomarkers we’ve studied for the detection of HCC,” Dr. Kisiel said. “We are seeking to apply this DNA assay technology to all cancers, and these findings are an important step toward that goal.”
Exact Sciences and Mayo Clinic have been collaborators since 2009. The collaboration previously yielded Cologuard, the stool-based, advanced-DNA screening test for colorectal cancer. The non-invasive test was approved by the U.S. Food and Drug Administration in 2014 and has been used by more than 1 million patients. Exact Sciences has identified biomarkers associated with 10 of the deadliest cancers and is advancing a pipeline of non-invasive diagnostic and screening tests based on those biomarkers.

Bluebird Bio’s Multiple Myeloma Data Reinforces Canaccord’s Bullish Thesis


Canaccord Genuity is maintaining its bullish stance on bluebird bio Inc BLUE 0.86% and projects upside for the biotech following a positive patient response to bb2121, the company’s multiple myeloma treatment.

The Analyst 

John Newman maintains a Buy rating on bluebird bio with a $250 price target.

The Thesis

The potential for the multiple myeloma treatment is just beginning to become visible, Newmansaid in a Monday note.
“As the drug moves earlier and is combined or sequenced with other therapies, we would expect a massive improvement in both [progression-free survival] and [overall survival],” the analyst said.
Bb2121 showed a median progression-free survival of 11.8 months, which fell in line with expectations, and the analyst said is impressive given the fact that the patients receiving the drug had already failed every therapy on the market.
Bluebird’s next data catalyst could come at the Amercian Society of Hematology conference in December in San Diego and should “allay any concerns on an efficiency level,” Newman said.

Intensive Outpatient Services Do Not Save Money


In the drive to reduce costs, some health systems have been testing intensive management models to augment primary care for high-risk, “sickest-of-the-sick” patients who might otherwise require expensive inpatient care. Now a new study suggests that any hoped-for savings may actually be elusive, although it could point to more effective ways in which resources might be directed.
The analysis included more than 2000 patients at five sites managed by the US Department of Veterans Affairs (VA) and showed that individuals who received care from an intensive management team working in conjunction with their usual primary care clinicians incurred no net changes in costs, but made greater use of outpatient services such as health coaching, home visits, and medication reconciliation than patients assigned to usual care, Jean Yoon, PhD, MHS, and coauthors write.
This shifting of costs from inpatient to outpatient care and the overall cost “neutrality” of the added intensive services suggest “that a potential exists to change how care is delivered,” they explain. “Primary care practices may consider implementing intensive management programs with these findings in mind.”
However, to realize their full potential, those intensive programs must be redesigned to maximize patient participation, the authors add. They publishedtheir findings online June 4 in the Annals of Internal Medicine.
Yoon, from the VA Health Economics Resource Center and Center for Innovation to Implementation, Menlo Park, California, and the University of California, San Francisco, School of Medicine, and coauthors conducted a randomized controlled, quality improvement trial at five VA sites in geographically diverse areas across the United States. The study included patients with a recent history of a visit to a hospital or emergency department, and a score in the 90th percentile for 90-day hospitalization on a validated risk-predicting algorithm.
The study recruited participants from July 21, 2014, to August 28, 2015, and randomly assigned them by site and sex to the intensive management team or to usual care. The intensive management team conducted patient evaluations, made care recommendations on the basis of those evaluations, and actively followed patients who accepted the intensive services in addition to their usual primary care. The authors compared resource utilization and costs for each patient during the 12 months before and the 12 months after their assignment.
The groups each consisted of 1105 patients. Men made up approximately 90% of each cohort, with a mean age of 63.3 years (standard deviation, 12.4) in the intensive-management group and 62.3 years (standard deviation, 12.7) in the usual-care group (P = .08). There were no significant differences in other baseline characteristics between the two groups.
In general, patients in the intensive management group were older, less likely to be never married, had higher rates of chronic illnesses such as diabetes and depression, had used more primary care services at baseline, and had lower rates of schizophrenia and drug or alcohol dependence compared with patients in the usual care group (all standardized mean differences, >0.01).
Only 487 (44%) of the patients in the intensive management group received the full intervention, which the authors defined as “three or more encounters in person or by telephone from the intensive management team.” These patients had a mean of 14.0 encounters (range, 3 – 116) compared with 0.4 (range, 0 – 2) experienced by the other individuals in that group. Most of the intensive interventions were for home care, social work services, and mental health or substance use disorder care.
Of the patients in the intensive management group, 204 (18%) did not fully participate or were offered only limited services, and the team determined that 414 (37%) would not benefit from those services or could not be contacted.

Few Differences Between Groups

On unadjusted analysis, patients in the intensive management group incurred a mean of $31,956 (95% confidence interval [CI], $29,480 – $34,433) in total healthcare costs in the 12 months before the study, and a mean of $31,878 (95% CI, $28,848 – $34,909) in the 12 months afterward. For patients in the usual care group, unadjusted mean costs were $32,536 (95% CI, $29,851 – $35,222) and $31,904 (95% CI, $28,528 – $35,280), respectively.
After adjustment for patient demographic factors and health conditions diagnosed during the year before randomization, total healthcare costs for patients in the intervention group were $471 (95% CI, −$6347 to $7290) higher than in the control group. Patients in the intervention group had higher mean adjusted costs for primary care, including home-based primary care, but lower costs for mental health intensive case management. There were no other significant cost differences between the groups.
The authors also found no significant differences between the groups in rates of hospitalization “with regard to mean number of inpatient stays, inpatient days, or emergency department visits in the postintervention period,” they write. Patients in the intensive management group did have significantly fewer nursing home days than the usual care group (incidence rate ratio, 0.35; 95% CI, 0.13 – 0.95). The intensive management group also made greater use of outpatient services such as primary care, care management, mental health and substance use disorder care, and home, geriatrics, and palliative or hospice care.
Mortality during the 12-month follow-up period in the intensive management and usual care groups was 5.9% vs 5.5%, respectively (P = .93).
“[O]verall, the intensive management programs seem to have been associated with cost shifting from inpatient to outpatient care,” the authors write. Thanks to the comprehensive assessments performed by the intensive management teams, the findings suggest that these programs “could identify unmet needs and connect patients to important resources.”
However, the authors add that patients with substance use disorders or more serious mental illnesses may find it harder to engage with the management team and may require different models of care.
Study limitations include inability to generalize from these five VA sites to the rest of the country, the possibility that a 12-month follow-up may have been insufficient for detecting significant changes in use of care, no information on prescription drug use or visits to non-VA sites, and lack of access to Medicare data.
Although the intensive management teams were able to help complex patients find outpatient services that met their needs, the fact that only 62% participated “suggests that better methods are needed to efficiently target the high-risk patients most likely to benefit from outpatient care,” the authors conclude. “Overall, our findings and those of other studies suggest that improvements in the design of intensive management programs are not only possible but necessary for this approach to achieve its full desired benefits.”
The authors have disclosed no relevant financial relationships.
Ann Intern Med. Published online June 4, 2018. Abstract