Cigna AI Product Identifies People Who Skip Medicines

Cigna Corp. plans to expand a system that uses artificial intelligence to identify gaps in treatment of chronic diseases, such as patients skipping their medications, and deliver personalized recommendations for specific patients.

The product, called Health Connect 360, integrates data from a combination of sources and analytical tools, some developed at Cigna and others brought in as part of its $54 billion acquisition of pharmacy-benefit manager Express Scripts Holding Co., completed late last year. Express Scripts, which began developing the service two years ago, rolled out portions of it to some customers this year.

The complete system will be available next month to all customers of Express Scripts and Cigna that offer health benefits to employees, the company said.

Health Connect 360 was developed for treatment of chronic diseases, including diabetes and heart disease, as well as for pain management. The system aggregates medical, pharmacy, lab and biometric data — such as information from glucometers, which measure blood-sugar levels — into a dashboard that is accessible through an online interface. The dashboard will be visible to the service’s customers and to Express Scripts case managers and nurses with access rights. The system can also feed information to electronic-medical record systems for physicians.

More health-care organizations are looking to artificial intelligence to spot diseases, prioritize cases and improve patient outcomes — results that also have the effect of lowering overall costs for the providers.

AI systems’ ability to learn from an array of patient histories, medical tests and diagnostic tests makes them ideal tools for care. However, getting access to health data required for better outcomes can be a bottleneck.

“That was our concept around the acquisition of Express Scripts — it was much more than just simply buying a pharmacy-benefits management [company]. It was buying a set of care-management capabilities, and access to data and intelligence that would be very, very hard to replicate,” said Cigna Chief Information Officer Mark Boxer, who drives the company’s AI deployment.

Cigna is already using AI to predict whether patients might abuse or overdose on prescription opioids. Another Cigna tool, One Guide, provides personalized help to health-insurance holders on their benefit plans, appointments and health coaching.

The new Health Connect 360 system combines algorithms that analyze data such as clinical and pharmacy information with predictive models to generate recommendations and ways to best engage a patient, whether through an app or in person.

For example, collected data from pharmacy claims or high blood glucose level readings from connected glucometers could trigger an alert in Health Connect 360 that a diabetic patient needs help to stay on track with medications.

After the system was tested and partially deployed this year, early results showed success in helping diabetic patients, the company said.

Managing chronic conditions is much less expensive than engaging in some kind of corrective procedure, said Matthew Josefowicz, chief executive of research and advisory firm Novarica Inc.

“Across the health-care industry, as with every industry, the incredible growth in data availability and ability to communicate enables new kinds of interventions that were just too cost-prohibitive to even consider before,” Mr. Josefowicz said.

To keep the focus on its core health business, Cigna recently has been seeking a buyer for a unit that sells life, accident and disability-income insurance to employers for their workers, The Wall Street Journal reported Tuesday.

https://www.marketscreener.com/CIGNA-CORPORATION-49690049/news/Cigna-AI-Product-Identifies-People-Who-Skip-Medicines-WSJ-29723195/

Turning stem cells to brain cells, Aspen Neuroscience hopes to undo Parkinson’s

The idea of a cell therapy for Parkinson’s disease starts out simple: Symptoms of the progressive disease are largely driven by the deaths of dopamine-producing neurons found deep within the brain. With lower levels of the neurotransmitter come the characteristic tremors, rigidity and slow movements.

By replacing those lost nerve cells with new dopamine producers, researchers hope to renew the brain’s connection to the body’s muscles and improve a person’s overall motor function.

But in the brain, everything becomes more complicated. On top of the risk of immune system rejection that comes with any kind of living tissue transplant, it’s important to make sure the implanted cells function correctly and do not pick up any dangerous genetic mutations as they grow.

Now, a new company, Aspen Neuroscience, aims to tackle both obstacles at once.

First, the startup hopes to avoid any harmful immune reactions by using a patient’s own cells as a starting point. Then, Aspen plans to implement a rigorous quality control program employing whole genome sequencing and artificial intelligence to make sure the cells stay in line as they’re processed and readied for the procedure.

And to do it, the San Diego-based company is starting out with $6.5 million in seed money plus an impressive roster of names.

They are led by neurology researcher Howard Federoff, previously vice chancellor for health affairs and CEO of the University of California, Irvine health system as well as the executive dean of medicine at Georgetown University. He’s joined by Aspen co-founder and stem cell scientist Jeanne Loring, founding director and professor emeritus of the Center for Regenerative Medicine at the Scripps Research Institute.

Meanwhile, the seed round was led by Domain Associates and Axon Ventures with additional backing from Alexandria Venture Investments, Arch Venture Partners, OrbiMed and Section 32.

Aspen looks to combine its expertise in stem cell biology, genomics and neurology to offer the first autologous cell therapy for Parkinson’s disease—while others in the space have pursued allogeneic routes, or therapies derived from donors other than the patient.

The process starts with a culture of the patient’s skin cells, which are then genetically induced to become pluripotent stem cells—or cells capable of differentiating into any other cell type in the body. These are then chemically nudged further to transform into precursor versions of the dopamine-producing neurons, which are typically found in the midbrain and regions responsible for the movement of limbs.

“We can say without any equivocation that we can produce the population of cells necessary to transplant, and in a short enough period of time to have a potential beneficial impact on the evolution of the disease,” said Federoff, who has also served as chair of the NIH’s Recombinant DNA Advisory Committee and helped lead the U.S. Parkinson’s Disease Gene Therapy Study Group.

“We envisage that this will set back the clock on patients who have Parkinson’s, unlike any other therapy that we know of,” he told FierceMedTech in an interview.

The number of cells needed would be much smaller compared to other cell therapies and cancer treatments. The healthy human brain contains only about 200,000 dopamine-producing nerve cells, split between its two hemispheres, while patients with Parkinson’s disease have lost about 50% or more of those neurons.

Aspen aims to evaluate two doses: one that aims to replace about 60% to 65% of a person’s normal cell complement and another larger treatment, Federoff said.

Those smaller doses, as well as starting with a patient’s donor cells, help make the treatment safer to produce by requiring fewer steps. Each cycle of cell division and multiplication to increase their numbers carries the risk of introducing genetic mutations.

As the cells are grown, they are consistently evaluated with data-driven techniques pioneered by Loring’s laboratory. Using whole genome RNA sequencing, Aspen will match the cells up at every stage with a genetic barcode taken from each patient at the start. This will allow them to look for changes, duplications or deletions in the pluripotent stem cell genome.

“If the cells harbor mutations that are cancer drivers, we don’t want to put those into people,” Loring said. “The only way is to check the sequencing before we transplant them.”

The cells used in the transplant procedure aren’t fully grown; as neuron progenitors, they mimic the development steps seen in the brain of a growing fetus after they’re placed in the body as they wire themselves up to other neural structures and begin to form new networks of their own.

“We anticipate that they will manufacture and release dopamine in a manner that is consistent with synaptic neurotransmission and the process of communicating from cell-to-cell,” said Federoff. “They will take up dopamine from synapses when it has done its business, bring it back into the cell, and prepare it for another synaptic release.”

“These are not just dopamine pumps, they’re real neurons,” added Loring. “They will genuinely replace the cells that have been lost in every way.”

Aspen plans to pursue two courses of therapy, for the two major types of Parkinson’s disease. Their lead candidate is for idiopathic, or sporadic Parkinson’s, while their second is a CRISPR-edited version of the therapy designed to address one of the disease’s most common genetic mutations, linked to about 5% of cases.

This would not only aim to restart dopamine production in this orphan indication, but also restore the damaged enzyme GBA, which is seen as an underlying cause. Federoff and Loring expect their sequencing-based quality check system will also help catch any off-target edits linked to the use of CRISPR-Cas9.

The company has yet to secure permission from the FDA to officially launch clinical trials, but the agency has signed off on Aspen’s plans to prepare a “trial-ready cohort” of Parkinson’s disease patients in the meantime. This would include the initial stages of recruitment and testing, including the selection of patients capable of having their skin cells made into pluripotent stem cells.

After it receives its go-ahead from the FDA, Aspen plans to hit the ground running, enrolling at least 176 participants in a phase 1/2 study that includes a randomized stage to determine clinical benefits.

https://www.fiercebiotech.com/medtech/by-turning-stem-cells-into-brain-cells-aspen-neuroscience-hopes-to-rewind-progress

Saliva test promising for earlier, easier detection of mouth and throat cancer

Cancers that occur in the back of the mouth and upper throat are often not diagnosed until they become advanced, partly because their location makes them difficult to see during routine clinical exams. A report in the Journal of Molecular Diagnostics, published by Elsevier, describes the use of acoustofluidics, a new non-invasive method that analyzes saliva for the presence of human papilloma virus (HPV)-16, the pathogenic strain associated with oropharyngeal cancers (OPCs). This novel technique detected OPC in whole saliva in 40 percent of patients tested and 80 percent of confirmed OPC patients.

“OPC has an approximate incidence of 115,000 cases per year worldwide and is one of the fastest-rising cancers in Western countries due to increasing HPV-related incidence, especially in younger patients. It is paramount that surveillance methods are developed to improve early detection and outcomes,” explained co-lead investigator Tony Jun Huang, PhD, Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC, USA.

“Considering these factors, the successful detection of HPV from salivary exosomes isolated by our acoustofluidic platform offers distinct advantages, including early detection, risk assessment, and screening,” added Dr. Huang. This technique may also help physicians predict which patients will respond well to radiation therapy or achieve longer progression-free survival.

Exosomes are tiny microvesicles originating within cells that are secreted into body fluids. They are believed to play a role in intercellular communication and their numbers are elevated in association with several types of cancers. Acoustofluidics is an advanced technology that fuses acoustics and microfluidics. Fluid samples are analyzed using a tiny acoustofluidic chip developed to isolate salivary exosomes by removing unwanted particles based on size, leaving exosome-rich concentrated samples that make it easier to detect tumor-specific biomarkers.

In this study investigators analyzed saliva samples from 10 patients diagnosed with HPV-OPC using traditional methods. They found that the technique identified the tumor biomarker HPV-16 DNA in 80 percent of the cases when coupled with droplet digit PCR. Since this method is independent of sample variability that arises due to changes in saliva viscosity and collection methods used, it may prove ideal for use in clinical settings.

Dr. Huang highlighted some of the technique’s features, including automated and fast exosome isolation (less than five minutes of processing time compared to approximately eight hours of processing time using benchmark technologies). Analyses can be performed at relatively low cost and at points of care. Also, it is suitable for repeated and continuous monitoring of tumor progression and treatment, unlike traditional biopsy.

“With these features, the acoustofluidic technology has the potential to significantly exceed current industry standards, address unmet needs in the field, help expedite exosome-related biomedical research, and aid in the discovery of new exosomal biomarkers,” commented Dr. Huang.

“The saliva exosome liquid biopsy is an effective early detection and risk assessment approach for OPC,” said co-lead investigator David T.W. Wong, DMD, DMSc, of the Center for Oral/Head and Neck Oncology Research, School of Dentistry at the University of California Los Angeles, CA, USA. “The acoustofluidic separation technique provides a fast, biocompatible, high-yield, high-purity, label-free method for exosome isolation from saliva.” According to the researchers, this technology can also be used to analyze other biofluids such as blood, urine, and plasma.

The study was an international collaboration between Duke University, UCLA, and University of Birmingham (UK). Prof Hisham Mehanna, Director of the Institute of Head and Neck Studies and Education, University of Birmingham, Birmingham, UK, said ‘The results are a testament to the power of interdisciplinary research and international collaboration.’

https://www.eurekalert.org/pub_releases/2019-12/e-sts121119.php

New IRS rule will help lower drug costs for those with chronic conditions

Life may get a bit easier for millions of Americans with chronic medical conditions who struggle to pay for their medical care.

The IRS recently released formal guidance that allows insurers who sponsor high-deductible health plans (HDHPs) linked to health savings accounts (HSAs) to cover 14 essential services used to treat chronic diseases like diabetes and asthma before patients hit their deductibles.

That’s a big, welcome change. Previously, insurance coverage did not kick in until most patients spent over a thousand dollars out of pocket. That’s right: While in the deductible phase, many people pay the full “retail” price for critically important—and often predictable—medical services.

Since up to 40% of Americans can’t afford an unexpected $400 bill, many people don’t visit their clinicians and stop filling their prescriptions for insulin, inhalers, statins and other common drugs that keep patients healthy and prevent expensive hospitalizations and surgeries.

By reducing out-of-pocket drug costs, this reform will make critical medications more accessible. That’ll improve health outcomes for millions of patients—and potentially reduce overall healthcare spending. Let’s hope insurers embrace this change so that chronic disease patients never have to pay full price for lifesaving medicines ever again.

HDHPs have become increasingly popular in recent years. It’s easy to see why. They offer lower premiums than traditional coverage by shifting costs to those who use medical care. And they enable consumers to open HSAs, a type of tax-advantaged savings and investment account.

By 2017, 25% of working-age adults with employer-sponsored coverage were enrolled in high-deductible plans, up from just 4% in 2007.

However, these plans don’t work well for many Americans with chronic diseases.

The plans subject patients to steep out of-pocket-costs, in addition to premiums. By law, enrollees must pay a minimum of $1,350 out-of-pocket before insurers step in to help. Some plans set deductibles even higher. This year, plans can require individuals to pay a maximum of $6,750 in out-of-pocket costs.

There’s an exception to this rule. Insurers can pay for “preventive” care before patients reach their deductibles, but until recently, preventive was narrowly defined. It included services such as flu shots or cancer screenings, but explicitly left out chronic disease treatments.

The new IRS guidance expanding what is considered preventive makes sense. For patients with chronic disease conditions, drugs and diagnostic tests are truly preventive. For instance, insulin can help diabetes patients avoid serious—and expensive—complications, including blindness and amputation.

Chronic disease patients enrolled in high-deductible plans could see their prescription expenses drop substantially. That’s welcome news, given the rising healthcare costs. Consider that between 2012 and 2016, patients with Type 1 diabetes saw their annual insulin costs nearly double to $5,700.

Patients who face high out-of-pocket costs often deviate from their doctor’s orders. Nearly a third of patients said they didn’t take their medicines as prescribed in the last year because of cost. Prescription non-adherence results in 125,000 deaths and costs our healthcare system up to $289 billion annually.

Each year, more and more Americans enroll in high-deductible plans. The new IRS guidance will help reduce non-adherence, improve health and potentially lower medical spending.

Dr. A. Mark Fendrick is director of the Center for Value-Based Insurance Design at the University of Michigan.

https://www.fiercehealthcare.com/payer/industry-voices-new-irs-rule-will-help-lower-drug-costs-for-those-chronic-conditions

7 providers join Blue Cross Blue Shield of Mich. new value-based care model

Blue Cross Blue Shield of Michigan announced it joined up with seven providers in the state to launch Blueprint for Affordability, a new value-based care program that includes both upside and downside financial risk.

Ascension Michigan, Henry Ford Health System, Michigan Medicine, Oakland Southfield Physicians, the Physician Alliance, Trinity Health – Michigan and United Physicians signed on to the model, which kicks off Jan. 1. It will last for five years.

Executives at the health plan said on a call with reporters Wednesday that the risk-sharing approach will encompass about 30% of its membership in commercial PPO and Medicare Advantage PPO plans largely in the southwest part of the state, representing about $4 billion in healthcare spend.

“What I think makes this program particularly significant, impactful and unique is the scale at which we are rolling it out,” Todd Van Tol, senior vice president of healthcare value at Blue Cross, said on the call. “We believe this is the largest value-based payment reform of its kind in any state in the nation.”

The providers who signed on to the model agreed to work toward annual targets for the cost of care they offer Blue Cross members. Those that come in under these targets will earn financial rewards, while those who exceed them will be asked to reimburse Blue Cross a portion of the excess spending.

Blueprint for Affordability builds on prior work spearheaded by Blue Cross in Michigan to control costs. The insurer said that its 50 existing value-based partnerships have saved $2.2 billion since 2015, leading it to lower premiums nine times in the past four years for small group customers and stabilizing rates in the individual markets and for Medicare Advantage.

Blue Cross said the shared accountability ensures incentives are aligned to promote better quality care at a lower cost, and the provider partners echoed that sentiment, saying on the call that it put them back in the driver’s seat in managing care.

“We know quality improvements like this work,” said Paul Castillo, chief financial officer at Michigan Medicine, on the call.

Blue Cross will bring its data capabilities to the partnership, which it says will allow providers to be more proactive in caring for patients. For example, instead of waiting for a patient to come in with the flu, a physician will have access to data that flags whether he or she had the flu last season that led to an inpatient stay—indicating it’s time to bring the patient in for a visit.

Over time, Blueprint for Affordability should improve the patient experience, boost care quality, reduce unneeded care and services and better coordinate care across the continuum, Blue Cross said.

“This program really builds on our experience as a plan,” Van Tol said.

https://www.fiercehealthcare.com/payer/7-providers-sign-to-blue-cross-blue-shield-michigan-s-new-value-based-care-model

CVS new precision medicine initiative to gene-test cancer patients

CVS is launching a new program aimed at boosting access to genetic testing for people with advanced cancers.

Through the Transform Oncology Care program, CVS is partnering with precision medicine company Tempus to make it easier for oncologists to offer advanced genomic tests to patients.

These broad panel tests identify more individual variations in cancer that allow docs to pinpoint the best treatment option.

Tempus’ platform also allows for rapid enrollment in clinical trials for eligible patients, CVS officials said.

The program will be available nationwide to health plans who contract with CVS Caremark, with Aetna launching it for participating provider networks in fully insured commercial plans across 12 states.

“This something our payers have asked for as a solution that is more comprehensive,” Prem Shah, executive vice president of specialty pharmacy for CVS Health, told FierceHealthcare.

He likened it to CVS’ existing work in kidney care—another disease state that payers were actively seeking solutions for. In April 2018, CVS announced that it would launch an initiative to prioritize early detection of kidney diseases and grow access to home dialysis.

Over the summer, it announced it would conduct clinical trials for its own home dialysis system, the HemoCare Hemodialysis System.

Oncologists will have access to clinical guidelines from the National Comprehensive Cancer Network in their provider portals, Shah said, which can ease the process in selecting a treatment plan as it’s built into existing e-prescribing workflows.

For those who would benefit from the advanced genomic testing, that will also be flagged in that portal. The program would also ease the need for prior authorization for certain treatment options or medications, Shah said.

In addition, the new program harnesses CVS’ local footprint and wealth of data to identify patients who may be at risk for cancer and could benefit from preventive interventions more quickly. Shah said the goal is to go “end to end” in cancer care, beginning with early prevention to screening and diagnosis to the end of life for advanced cancers.

CVS will also offer nurse-led care management as part of the program—which can identify potential gaps in care—that’s integrated into a health plan’s existing programs as well as the opportunity for value-based contracting with oncology providers.

“This is a critical pain point for the marketplace,” Shah said. “We think that this is a very strategic solution that’s going to bear fruit for patients, payers and providers.”

https://www.fiercehealthcare.com/payer/cvs-unveils-new-precision-medicine-initiative-for-oncology-patients

SABCS 2019 – Tecentriq stumbles in triple negative disease

Disappointing data in a small neoadjuvant trial testing Tecentriq in triple negative breast cancer suggests that once again Keytruda may have an edge.

Roche’s Tecentriq is the only anti-PD(L)1 antibody to have won approval in triple negative breast cancer, but the extent to which these checkpoint inhibitors will play a role in this disease remains unclear. Disappointing data from a small neoadjuvant trial underline this fact: Tecentriq failed to improve response rates over chemotherapy, it was announced today, a finding that stands in contrast to Keytruda’s success in a similar trial.

Cross-trial comparisons always come with caveats: chemotherapy regimens differed in this case, for example. But investigators presenting the results at the San Antonio Breast Cancer Symposium were unsure why patients responded differently to the two therapies.

The Tecentriq data come from the first look at the NeoTRIPaPDL1 trial. Adding Tecentriq to neoadjuvant chemotherapy for approximately six months resulted in a slightly higher rate of pathologic complete response versus neoadjuvant chemo alone, but the difference was not statistically significant.

The academic study enrolled 280 patients with early high-risk and locally advanced or inflammatory triple-negative breast cancer. The chemo regimen in the trial was carboplatin and Abraxane; Tecentriq is already approved for use with Abraxane in some patients with locally advanced or metastatic triple-negative breast cancer.

In the very similar Keynote-522, a phase III study of neoadjuvant Keytruda plus chemo followed by adjuvant Keytruda in early triple-negative disease, Merck’s checkpoint inhibitor did yield a significant improvement in responses over chemo alone. Intriguingly in Keynote-522 the chemo arm also responded at a higher rate than NeoTRIPaPDL1’s control arm.

HIT AND MISS: TECENTRIQ VS KEYTRUDA IN TNBC
	NeoTRIPaPDL1			Keynote-522*
	Tecentriq + chemo	Chemo alone	P value	Keytruda + chemo	Chemo alone	P value
pCR	43.5%	40.8%	0.66	64.8%	51.2%	0.00055
pCR in PD-L1+ patients	51.9%	48.0%	Not given	68.9%	54.9%	Not given
*Results presented at Esmo 2019. pCR=pathologic complete response. Source: SABCS 2019, Esmo 2019.

Presenting the NeoTRIPaPDL1 data at SABCS, Luca Gianni of the Fondazione Michelangelo in Milan, seemed to suggest that this could be down to the drugs being different. He pointed out that Keytruda is directed against PD-1 while Tecentriq binds this receptor’s ligand.

“At the end of the day they both interfere with the access between PD-1 and PD-L1, and it is largely assumed that mechanistically they will have the same effect, although there are subtle differences that may be not so subtle at the end of the day,” Dr Gianni said in a press conference.

It is also worth noting that the chemo regimens were different between the two trials, with Keynote-522 including another round of chemotherapy, post carboplatin and Abraxane. This presumably contributed to the higher response rate in Keynote-522’s control group, and could well have boosted the responses in the active arm.

Pathologic complete response is not the primary endpoint of either trial – it is merely considered a surrogate for long-term outcomes. Instead both are using event-free survival as the main outcome, measured at five years for NeoTRIPaPDL1, with full data due in 2022; Keynote-522’s event-free survival is measured at “up to approximately eight years”, its clinicaltrials.gov record says, with full data in 2025.

Coming up

Complicating the picture still further, a subgroup analysis of Keynote-522 also read out positively for Merck’s blockbuster at SABCS today. Among triple-negative breast cancer patients whose cancers had spread to the lymph nodes, 64.8% responded when Keytruda was added to chemo, compared with 44.1% given chemo alone.

The sellside sees breast cancer as a much bigger opportunity for Keytruda than Tecentriq; 2024 forecasts sales in the indication are $3bn for the former versus just  $247m for Tecentriq. However, neoadjuvant use in triple-negative disease will only make up a fraction of these forecasts.

Perhaps more important is the forthcoming readout of the Keynote-355 in the first-line setting. Tecentriq’s first-line breast cancer study, Impassion-130, showed strong results in PD-L1-positive patients and was duly approved here, but a wider label has eluded the Roche product (Esmo 2018 – Roche misses the bullseye in triple-negative breast cancer, October 20, 2018). It is expected that Keytruda will best Tecentriq here too.

Lastly there is Impassion-031, Roche’s effort at proving Tecentriq’s worth in the neoadjuvant setting. The trial design is different, with Impassion-031 focusing on pathologic complete response in all-comers and PD-L1-high patients, without Keynote-522’s focus on event-free survival. The trials’ chemo arms are also subtly different, which will make it hard to be certain of the two checkpoint inhibitors’ relative merits.

SELECTED UPCOMING STUDIES OF TECENTRIQ AND KEYTRUDA IN BREAST CANCER
Study	Treatment	Setting	Trial ID	Results
Impassion-130	Tecentriq + chemo	1st-line	NCT02425891	Mar 2019: US approval in PD-L1+ve patients
Keynote-355	Keytruda + chemo	1st-line	NCT02819518	Dec 2019
Keynote-522	Keytruda + chemo	Neoadjuvant	NCT03036488	Hit on pCR toplined Jul 2019
NeoTRIPaPDL1*	Tecentriq + chemo	Neoadjuvant	NCT02620280	Miss on pCR Dec 2019
Impassion-031	Tecentriq + chemo	Neoadjuvant	NCT03197935	Sep 2020
MO39875	Tecentriq + chemo	Neoadjuvant	NCT03281954	Dec 2023
Impassion-030	Tecentriq + chemo	Adjuvant	NCT03498716	Jan 2022
Keynote-242	Keytruda	Adjuvant	NCT02954874	May 2026
*Academic trial. Source: Clinicaltrials.gov.

https://www.evaluate.com/vantage/articles/events/conferences/sabcs-2019-tecentriq-stumbles-triple-negative-disease