CMS Experimenting With New Accountable Care Organization Model, FDA Updates, and more

CMS Experimenting With New Accountable Care Organization Model

The Centers for Medicare & Medicaid Services (CMS) announced the Medicare−Medicaid Accountable Care Organization (ACO) Model, which is a new initiative designed to improve the quality of care and lower costs for beneficiaries. It builds on the Medicare Shared Savings Program, in which Medicare ACOs that hit spending and quality targets can share in the savings with CMS, and it advances efforts to partner with states in transforming the health-care delivery system.

“This model aims to provide improved care coordination for those enrolled in both Medicare and Medicaid, allowing providers to focus more on providing care for their patients rather than administrative work,” said Patrick Conway, MD, MSc, acting principal deputy administrator at CMS.

CMS is accepting letters of intent from states that wish to partner to design certain state-specific elements of the model and intends to enter agreements with as many as six states, with preference given to those with low saturation of providers already participating in a Medicare ACO program. Once a state is approved to participate in the model, a request for application will be released to ACOs and health-care providers in that state.

The deadlines to submit letters of intent are January 20, 2017, for 2018 performance start date, August 4, 2017, for 2019 start date, and August 3, 2018, for 2020 start date.

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Source: CMS press release, December 15, 2016.

Proof-of-Concept Trial of Artificial Blood Product Erythromer Meets Primary Efficacy Endpoint

Results from a proof-of-concept trial of erythromer, a nanoscale biosynthetic artificial red blood cell (RBC) product, show that the product successfully emulated the functions of natural RBCs. If proven safe in humans, the blood substitute could be used for transfusions in cases in which stored blood is unavailable or unusable, according to the authors, led by Dipanjan Pan, PhD, of the University of Illinois at Urbana-Champaign.

“Unfortunately, all prior blood substitutes have failed due to two flaws: poor oxygen delivery to tissue and vasoconstriction,” co-author Allan Doctor, MD, of the Departments of Pediatrics and Biochemistry at the Washington University in Saint Louis in Missouri, said during his presentation of the results at the 2016 ASH Annual Meeting. “Improvements in synthetic chemistry and nanomedicine have enabled us to encapsulate human hemoglobin with a suite of small molecules that we can encode with ‘wet-ware’ that helps coordinate normal behavior in the particle, simulating red blood cells.”

This “wet-ware” links erythromer’s oxygen binding ability to changes in blood pH, thus allowing the lungs to dispense oxygen to tissues with the greatest need. Erythromer cells are designed to be “freeze-dried,” stored at ambient temperatures, and reconstituted with water when needed.

Dr. Pan and researchers conducted ex vivo and in vivo testing in rodent models to determine if the artificial RBC product could match an erythrocyte’s natural physiologic functions, including measures of payload retention, biocompatibility, oxygen affinity, and nitric oxide consumption. Erythromer performed well on these tests, “suggesting that this design surmounts prior challenges” of artificial blood product design.

Pharmacokinetic analyses showed that the distribution half-life was 26.2±3.6 minutes and elimination half-life was 300±12 minutes, which the authors noted would likely translate to a half-life in humans of approximately three hours.

“Erythromer’s potential for extended ambient dry storage has significant implications for portability and use,” the authors concluded. “Next steps include testing if the formulation can be scaled up; a detailed study of pharmacokinetics, biodistribution, and safety; as well as [an] evaluation of hemorrhagic shock in large animal models.”

Source: Pan D, Rogers S, Misra S, et al. Erythromer (EM), a nanoscale bio-synthetic artificial red cell: Proof of concept and in vivo efficacy result. Abstract #1027. Presented at the ASH Annual Meeting and Exhibition, December 5, 2016; San Diego, CA.

FDA Halts Phase I Trials of Vadastuximab Talirine in AML

The U.S. Food and Drug Administration (FDA) has placed clinical holds on several phase I trials of vadastuximab talirine (SGN-CD33A) in patients with acute myeloid leukemia (AML), according to the drug’s manufacturer, Seattle Genetics.

The clinical holds were initiated to assess the risk of hepatotoxicity with vadastuximab talirine (a CD33-directed antibody drug conjugate) following the deaths of four patients who were treated with vadastuximab talirine along with allogeneic hematopoietic cell transplant (alloHCT) either prior to or following treatment. All four of these patients had veno-occlusive disease at the time of death; two additional trial participants also had hepatotoxicity.

The drug’s manufacturer reported that the phase I/II trial of single-agent vadastuximab talirine in pre- and post-alloHCT patients with AML has been placed on full clinical hold, while two other phase I trials have received partial clinical holds, meaning no further enrollment is allowed, but enrolled patients who consent can continue therapy. One of these trials is assessing vadastuximab talirine in combination with hypomethylating agents in older patients with AML; the other is examining vadastuximab talirine in combination with 7+3 chemotherapy in patients with newly diagnosed AML.

Other ongoing trials of vadastuximab talirine (the phase III CASCADE trial in older AML patients and phase I/II trial in myelodysplastic syndromes) are proceeding with enrollment.

At the 2016 ASH Annual Meeting, researchers reported data from the phase Ib trial of vadastuximab talirine in combination with 7+3 chemotherapy, finding that the drug was safe in patients with newly diagnosed AML, with patients showing no evidence of increased toxicity or mortality when the drug was added to the standard 7+3 regimen. Seventy-six percent of the 42 patients in this trial also achieved a response, with 60 percent achieving complete remission and 17 percent achieving remission with incomplete blood count recovery.

Source: Seattle Genetics press release, December 27, 2016.

FDA Grants Full Approval for Ponatinib and Its Updated Label

The FDA granted full approval of ponatinib for adults with chronic-phase (CP), accelerated-phase, or blast-phase chronic myeloid leukemia (CML) or Philadelphia chromosome-positive acute lymphocytic leukemia (Ph+ ALL) when no other tyrosine kinase inhibitor is indicated. Ponatinib also is approved to treat adults with T315I-positive CML or T315I-positive Ph+ ALL.

Ponatinib was granted accelerated approval in December 2012.

The full approval and label update are based on results from the phase II PACE trial, in which 449 heavily pretreated patients (refractory to dasatinib or nilotinib) with resistant or intolerant CML or Ph+ ALL were followed for 48 months (data cutoff was on August 2015).

Thirty percent of all patients (n=133/449; median follow-up = 37.3 months; range = 0.1-58.5 months) and 41 percent of patients with CP-CML (n=110/270; median follow-up = 48.2 months; range = 0.1-58.5 months) remained on the study at the time of data cut-off. For patients with CP-CML, the estimated four-year progression-free survival was 56 percent and overall survival (OS) was 77 percent. Patients with accelerated-phase disease had an estimated four-year OS of 51 percent, while the median OS was 6.9 months for patients with blast-phase CML/Ph+ ALL (95% CI 5.0-9.2).

The most common treatment-related adverse events (occurring in ≥30%) included thrombocytopenia (44%), abdominal pain (43%), rash (42%), constipation (37%), headache (37%), dry skin (36%), fatigue (30%), and hypertension (30%).

On October 10, 2013, a partial clinical hold was placed on new patient enrollment in clinical trials of ponatinib due to arterial thrombotic events that occurred after longer follow-up. In 2014, the FDA partial clinical hold was lifted and study enrollment continued.

Sources: FDA news release, November 30, 2016; Cortes JE, Pinilla-Ibarz J, Le Coutre PD, et al. 4-year results of the ponatinib phase II PACE trial in patients (pts) with heavily pretreated leukemia. Abstract #7013. Presented at the 2016 ASCO Annual Meeting, June 6, 2016; Chicago, IL.

CMS No Longer Testing Medicare Part B Drug Reimbursement Model

CMS discontinued its plan to test the Medicare Part B drug reimbursement model – an effort launched last March to address rising drug costs.
Medicare Part B pays for drugs that are administered in a physician’s office or hospital outpatient department, reimbursing the physician based on the drug’s average sales price (ASP) plus a 6 percent additional payment. CMS officials argued that this payment structure may incentivize physicians to choose a higher-priced drug.

The proposed rule would change this payment to 102.5 percent of the ASP plus a flat-fee payment of $16.80 per drug per day – an amount CMS calculated to be budget-neutral in aggregate – to see if this reimbursement rate changes prescribing behavior and leads to improved quality and value.

“While CMS was working to address these concerns, the complexity of the issues and the limited time available led to the decision not to finalize the rule at this time,” said Benjamin Wakana, a spokesperson for the Department of Health and Human Services.

The proposed model received opposition from the pharmaceutical industry, American Medical Association, and various medical and hospital groups, as they argued that some doctors would lose money if they were to provide costly drugs under the test, forcing them to send patients to other sites for care.

The proposed policy, which was intended to run for five years, mandated participation through two phases:

  • In the first phase, each of the 7,000 “primary-care service areas,” which are clusters of zip codes based on patterns of Medicare Part B primary-care services, would be randomly assigned to two groups: One would continue to receive payment under the existing policy, while the other would be reimbursed at the new rate.
  • In the second phase, which was set to begin in early 2017, CMS would test several different payment policies that would deviate from the ASP policy.
    Some organizations, such as the AARP, supported the model. “While more definitive study is needed, AARP believes the likelihood that the current methodology is influencing providers to use more expensive drugs over less expensive alternatives is reason enough to warrant change,” said David M. Certner, legislative counsel and legislative policy director for government affairs at AARP.

Sources: Roll Call, December 15, 2016; CMS Fact Sheet: CMS proposes to test new Medicare Part B prescription drug models to improve quality of care and deliver better value for Medicare beneficiaries.