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Thursday, December 12, 2019

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.’

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.

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.

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.”

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 + chemoChemo aloneP valueKeytruda + chemoChemo aloneP value
pCR43.5%40.8%0.6664.8%51.2%0.00055
pCR in PD-L1+ patients51.9%48.0%Not given68.9%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
StudyTreatmentSettingTrial IDResults
Impassion-130Tecentriq + chemo1st-lineNCT02425891Mar 2019: US approval in PD-L1+ve patients
Keynote-355Keytruda + chemo1st-lineNCT02819518Dec 2019
Keynote-522Keytruda + chemoNeoadjuvantNCT03036488Hit on pCR toplined Jul 2019
NeoTRIPaPDL1*Tecentriq + chemoNeoadjuvantNCT02620280Miss on pCR Dec 2019
Impassion-031Tecentriq + chemoNeoadjuvantNCT03197935Sep 2020
MO39875Tecentriq + chemoNeoadjuvantNCT03281954Dec 2023
Impassion-030Tecentriq + chemoAdjuvantNCT03498716Jan 2022
Keynote-242KeytrudaAdjuvantNCT02954874May 2026
*Academic trial. Source: Clinicaltrials.gov.

Opiant nabs second tranche of BARDA contract for nasal nalmefene

U.S. Health and Human Services unit BARDA has awarded the second tranche of its contract with Opiant Pharmaceuticals (NASDAQ:OPNT), valued at ~$2.4M, to accelerate the development of nasal nalmefene for the potential treatment of opioid overdose.
The total agreement is valued up to a maximum of ~$4.6M, the balance to be funded next year.
The company expects to file a U.S. marketing application in Q4 2020.

Sarepta spikes after accelerated FDA approval of Duchenne treatment

Sarepta Therapeutics (NASDAQ:SRPT+23.4% after-hours on news the Food and Drug Administration granted accelerated approval to the company’s Vyondys 53 (golodirsen) injection to treat a rare Duchenne muscular dystrophy mutation.
In making its decision, the FDA says it considered the potential risks associated with the drug, the life-threatening and debilitating nature of the disease and the lack of available therapy.
As part of the accelerated approval process, the FDA requires SRPT to conduct a clinical trial to confirm the drug’s clinical benefit.