FDA Approves Carfilzomib, Court Rules on Off-Label Drug Use, ABIM Reform, and more

FDA Approves Carfilzomib for Second-Line Multiple Myeloma

The U.S. FDA has approved expanded use of carfilzomib for the treatment of multiple myeloma when used in combination with lenalidomide and dexamethasone. The regimen is approved in patients who have received one to three prior lines of therapy. The expanded approval was based on the results of the phase III ASPIRE trial, published in The New England Journal of Medicine, which included 792 patients. Patients treated with carfilzomib plus lenalidomide and dexamethasone had longer progression-free survival, overall survival, and overall response rates than those treated with lenalidomide and dexamethasone alone. The trial also found that the carfilzomib combination group reported superior health-related quality of life. Carfilzomib has been previously approved by the U.S. FDA as a single agent for treatment of multiple myeloma in patients who have received at least two prior therapies, including bortezomib and an immunomodulatory agent, and in those who have progressed on or within 60 days of the last therapy.

Source: U.S. FDA press release

Medicare Testing New Model that Combines Hospice and Treatment

The Centers for Medicare & Medicaid Services (CMS) launched a new pilot program, the Medicare Care Choices Model, to provide a new option for dually eligible Medicare beneficiaries (those who are also eligible for Medicaid) to receive palliative care services from certain hospice providers, while still receiving services provided by their established care providers.

Under the current payment rules, older adults with a terminal disease must forgo aggressive disease-directed therapy to receive services under the hospice benefit. Currently, less than half of Medicare beneficiaries elect to use hospice care and most only do so for a short period of time.

The program is designed to:

  • Increase access to supportive care services provided by hospice
  • Improve the quality of life and patient/family satisfaction
  • Inform new payment systems for the Medicare and Medicaid programs

The program will affect the care of approximately 150,000 Medicare beneficiaries over the next four years, including patients with advanced cancers, chronic obstructive pulmonary disease, congestive heart failure, and HIV/AIDS.

Services under this new model will begin on January 1, 2016, for the first phase of participating hospices, with more than 140 Medicare-certified hospices included in the trial. Services will be available around the clock every day of the year, and CMS will pay a per-beneficiary per-month fee ranging from $200 to $400 to participating hospices under this new model.

Patrick Conway, MD, MSc, the principal deputy administrator and chief medical officer at CMS said in a New York Times article, “If [the program] is successful, and we think it will be, it is a strong evidence base to potentially scale it to the entire Medicare population.”

CMS is also monitoring the cost of patients in the program compared with those receiving traditional medical benefits.

Sources: U.S. Department of Health and Human Services; The New York Times

Bill to Reduce EHR and Meaningful Use Burden Introduced in the House

The Further Flexibility in HIT Reporting and Advancing Interoperability Act (Flex-IT 2) was introduced in the House of Representatives to reduce the growing regulatory burdens of meaningful use of electronic health records (EHRs), specifically eliminating the all-or-nothing approach to assessment of performance measures in the program rather than allowing physicians to earn credit for achieving part of the measures. This would also extend the 90-day reporting window to 2016 and beyond. In addition, the proposed bill would subject some EHRs to interoperability testing.

Flex-IT 2 would also prohibit the Centers for Medicare & Medicaid Services from announcing a final rule on January 1, 2017, unless one of the following two conditions have been met:

  • 75 percent of eligible physicians or hospitals meet stage two criteria
  • Merit-Based Incentive Payment System standards are in place

Many medical organizations, including the American Academy of Family Practitioners (AAFP) and the American Medical Association (AMA), have supported this revision.

“These common-sense policies would strengthen [meaningful use], prevent physicians from being unfairly penalized, and increase program participation,” according to a letter from AAFP that was sent to Representative Renee Ellmers from North Carolina, who is sponsoring the bill.

Steven J. Stack, MD, the president of AMA, said, “This important bill addresses many of the fundamental shortcomings in government regulations that have made many EHR systems very difficult to use. We heard loud and clear from physicians at the AMA’s first-ever town hall meeting on EHRs and meaningful use program that the systems they use are cumbersome, poorly designed, and unable to ‘talk’ to each other, thereby preventing necessary transmission of patient medical information.”

Sources: American Academy of Family Practitioners, “House bill aims to ease meaningful use burden,” August 7, 2015; American Medical Association, “AMA supports legislative effort to revise the meaningful use program,” July 30, 2015; Congress.gov.

IMWG Updates International Staging System for Multiple Myeloma

The International Myeloma Working Group (IMWG) has revised the International Staging System, a risk stratification (ISS) algorithm to assess the progression of myeloma in newly diagnosed patients and to determine the appropriate course of treatment. The researchers at IMWG analyzed clinical and laboratory data from 4,445 patients with newly diagnosed multiple myeloma from 11 international clinical trials. According to the full report, published in the Journal of Clinical Oncology, the revised guidelines add tests for chromosomal abnormalities and serum lactate dehydrogenase (LDH) to the earlier ISS to refine its prognostic value in newly diagnosed patients. The two new tests determine more definitively whether a patient is in stage three, while conversely, per the new protocols, a patient with stage one myeloma would have normal chromosomes and LDH.

The original ISS, published in 2005, was based only on serum ß2-microglobulin and serum albumin levels, though chromosomal abnormalities and LDH levels are key elements to characterizing the biologic features of multiple myeloma. “The revised staging system can be used by doctors to discuss prognostic results very carefully with individual patients,” said Brian G. M. Durie, MD, chairman of IMWG and the International Myeloma Foundation. “The revised staging system can be used by doctors to discuss prognostic results very carefully with individual patients,” said Brian G. M. Durie, MD, chairman of IMWG and the International Myeloma Foundation. “It’s helpful to know the expectations and to consider how treatments can be modified based on the new ISS system.”

Source: Palumbo A, Avet-Loiseau, Oliva S, et al. Revised International Staging System for multiple myeloma: a report from International Myeloma Working Group. J Clin Oncol. 2015 August 3. [Epub ahead of print]

Court Rules FDA Cannot Block Pharma Companies from Advertising a Drug for Off-Label Use

In early August, a federal judge in Manhattan ruled that the U.S. FDA cannot prohibit pharmaceutical companies from promoting unapproved indications for a drug because doing so would violate free speech protections.

“This is the first decision that clearly and unequivocally rebuffs the government’s view that off-label promotion can be prosecuted, even if truthful and non-misleading,” said Joel Kurtzberg, a lawyer who represented the drug manufacturer Amarin, the plaintiff in the case, in a New York Times article.

According to the decision, Amarin has the First Amendment right to give doctors truthful information about non-approved indications of its drug Vascepa®, which is used to lower a certain kind of fat. Currently, drugmakers are not allowed to advertise drugs for “off-label” uses, but companies’ ability to distribute independent materials about their drugs – such as medical journal articles – has been subject to legal debate for years.

In response to the ruling, the FDA said it is working on new guidelines; the agency has 60 days to appeal the decision.

Critics of this decision fear that allowing off-label promotions would undermine the incentives for companies to execute the studies necessary to win approval for new diseases, and the definition of truthful information may be ambiguous.

The legal decision applies only to the second U.S. Circuit Court of Appeals in New York, Connecticut, and Vermont, though, and experts pointed out that the FDA did not take issue with many of the company’s plans, and would have permitted them if the company had consulted regulators prior to filing the lawsuit.

Source: The New York Times, “Court forbids F.D.A. from blocking truthful promotion of drug.” August 7, 2015.

Medicare Reverses Position, Will Pay for Blinatumomab

Despite an earlier decision not to cover blinatumomab, a drug used to treat certain acute leukemias, the Centers for Medicare & Medicaid Services announced it will more extensively cover the expensive cancer drug beginning October 1, 2015.

Blinatumomab was approved by the U.S. FDA in December 2014 for the treatment of Philadelphia chromosome-negative relapsed or refractory B-cell precursor acute lymphocytic leukemia. The drug, which is delivered via intravenous infusion, costs approximately $178,000 per treatment course and is recommended for at least two 28-day cycles with two weeks of no treatment in between. A hospital stay for a portion of these treatment cycles is required for monitoring of side effects. Under the new rule, Medicare announced that it will also now allow an add-on technology to hospitals for this drug under the new rule – amounting to an additional $27,000 for the use of this drug. This additional payment will be in place for as many as three years, by which time the cost of the drug will be accounted for under the hospital accounting systems.

The final rule covering payments for inpatient hospital stays for Medicare patients for fiscal year 2016 was published in the Federal Register on August 17, and noted that blinatumomab “is not substantially similar” to other drugs available for this patient population and “represents a substantial clinical improvement over existing treatment options.”

Source: The New York Times, “Medicare, reversing itself, will pay more for an expensive new cancer drug.” August 8, 2015.

NIH Issues Requests for Applications Regarding Sickle Cell Disease

The U.S. Department of Health and Human Services (HHS) has submitted two new National Institutes of Health requests for applications regarding sickle cell disease (SCD).

  • Sickle cell disease implementation consortium (SCDIC): Using implementation science to optimize care of adolescents and adults with SCD (U01); HHS (RFA-HL-16-010)
    • Purpose: Improve the health and well-being of adolescents and adults with SCD in the United States through the development of multimodal, multisector interventions aimed at improving the rate at which patients with SCD receive routine primary care.
    • Design: In the initial phase 1, the clinical sites will use the methodologies of implementation research to (1) conduct a needs-based community assessment of the barriers to care for subjects with SCD; (2) design implementation research studies that address the identified issues of importance; and (3) participate in the development of a SCD registry.
    • Dates: Posted on July 15, 2015; open date starting October 12, 2015; letter of intent due October 12, 2015; application due November 12, 2015.
  • Data coordinating center for SCDIC: Using implementation science to optimize care of adolescents and adults with SCD (U24; RFA-HL-16-011)
    • Data coordinating centers will assist the SCDIC by coordinating the program and providing administrative and operational support by helping to develop the SCD registry and protocols, developing the SCDIC operating procedures and manuals of operations for each protocol, developing and implementing web communication tools, data management and associated training, data compilation into databases, analysis of data, and helping with the development of presentations and publications.
    • Dates: Posted on July 15, 2015; open date starting October 12, 2015; letter of intent due October 12, 2015; application due November 12, 2015.

Source: U.S. Department of Health and Human Services

FDA Approves Brentuximab Vedotin for Post-Auto-HSCT in Patients with Hodgkin Lymphoma

The U.S. FDA approved brentuximab vedotin for the post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation treatment of patients with classical Hodgkin lymphoma at high risk of relapse or progression. The approval was based on the results of a randomized, double-blind, placebo-controlled trial that included 329 patients with classical Hodgkin lymphoma. After auto-HSCT, patients were randomized 1:1 to receive brentuximab vedotin or placebo once every three weeks for a maximum of 16 cycles. The median progression-free survival in the brentuximab vedotin cohort was 42.9 months, compared with 24.1 months in the control group (hazard ratio=0.57; 95% CI 0.40-0.81; p=0.001). The most commonly reported treatment-associated adverse events for the brentuximab vedotin group were neutropenia, peripheral sensory neuropathy, thrombocytopenia, anemia, upper respiratory tract infection, fatigue, peripheral motor neuropathy, nausea, cough, and diarrhea. The most commonly reported serious adverse events included pneumonia, pyrexia, vomiting, nausea, hepatotoxicity, and peripheral sensory neuropathy. Of the patients in the brentuximab vedotin group, infusion-related reactions were reported in 15 percent of patients (n=25) and pulmonary toxicity was reported in five percent of patients (n=8).

Source: U.S. FDA press release

First Study to Show T-Cell Therapy Response in Multiple Myeloma

A new study published in Nature Medicine indicated that T-cell receptor therapy using a patient’s own immune system to recognize and destroy cancer cells demonstrated a clinical response in 80 percent of multiple myeloma patients with advanced disease who had undergone autologous stem cell transplants (ASCT).

The phase I/II clinical trial included 20 patients who received an average of 2.4 billion NY-ESO-engineered CD3 T-cell two days after ASCT. After a median follow-up of 21.1 months, 15 patients were alive, and 10 patients remained progression-free; at 30.1 months of follow-up, the median progression-free survival was 19.1 months and the median overall survival was 32.1 months. In addition, 14 patients (70%) had near complete responses, while two had a very good partial response. The researchers noted that the response rate was better than would be expected for standard ASCT.

“This study suggests that treatment with engineered T cells is not only safe but of potential clinical benefit to patients with certain types of aggressive [MM],” said Aaron P. Rapoport, MD, the director of the blood and marrow transplant program at the University of Maryland Marlene and Stewart Greenebaum Cancer Center, in a news release.

Source: Rapoport A, Stadtmauer EA, Binder-Scholl GK, et al. NY-ESO-1–specific TCR–engineered T cells mediate sustained antigen-specific antitumor effects in myeloma. Nat Med. 2015;21:914-21.

Proof-of-Concept Study Shows Blood Samples Safely Delivered Via Drone

Researchers at Johns Hopkins University School of Medicine experimented with the concept of using drones to deliver blood samples. A total of 336 blood samples were obtained from 56 healthy adult volunteers, which were then driven to a flight site an hour away from the hospital. Half of the samples were loaded onto the drone, and half remained stationary on the ground. The samples loaded on the drone then flew on a mile loop and stayed in the air from six to 38 minutes. All samples were then driven back to the laboratory where they underwent 33 common blood tests.

The researchers did not detect much of a difference between the samples that had been flown on the drones and those that stayed on the ground. The overall concordance was 97 percent, and the length of the drone flight had no impact on the blood sample results. Only one test, for total carbon dioxide, had results that varied.

According to Timothy Amukele, MD, PhD, a pathologist at Johns Hopkins who was involved in the study, said, “If we now have a cheaper way to move samples, it is a good thing, especially for patients who are hard to reach, whether they live in rural areas or places without good roads.” Next steps for this study include applying this concept to a pilot study with real patients in real clinical settings.

Source: Amukele TK, Sokoll LJ, Pepper D, et al. Can unmanned aerial systems (drones) be used for the routine transport of chemistry, hematology, and coagulation laboratory specimens? PLoS One. 2015 July 29. [Epub ahead of print]

FDA Proposes New Quality Monitoring Protocol to Prevent Drug Shortages

The U.S. FDA, in conjunction with the Center for Drug Evaluation and Research and the Center for Biologics Evaluation and Research, issued a draft guidance to address the problem of drug shortages by applying metrics to evaluate the quality of the facilities and production processes involved in making the branded, generic, and biologic prescription medications.

According to the draft guidance, pharmaceutical manufacturers would compile data on the FDA’s set of metrics, and the FDA would then collect records to conduct “risk-based inspection scheduling,” in which facilities with highly controlled manufacturing processes would have the potential to be inspected less often than similar establishments that demonstrate uncontrolled processes.

“It is critically important for patients, health-care professionals, caregivers, payers, and others to have confidence in how medications are made,” according to Ashley Boam, the acting director of pharmaceutical quality policy at the FDA, and Mary Malarkey, the director of biologics quality compliance at the FDA. “Quality metrics can help us achieve this goal.”

As of June 30, there were 219 active drug shortages in the United States, representing a 44 percent increase over the reported 152 drug shortages in 2010. However, the shortages have decreased since the end of 2014 when active drug shortages were reported at more than 300.

The draft letter noted, “The agency has found that the majority of drug shortages stem from quality concerns – substandard manufacturing facilities or processes are discovered, or significant quality defects are identified in finished product, necessitating an interruption in production and a shortage of drugs.”

The FDA is taking public commentary on this initiative through September 2015.

Source: U.S. FDA, “Request for Quality Metrics: Guidance for Industry,” August 3, 2015.

ABIM Clarifies Board Certification and Enrollment in MOC Status

The American Board of Internal Medicine (ABIM) has announced a change to its controversial maintenance of certification (MOC) rules. Following a revision of the MOC program in January 2014 that attempted to simplify the fee structure by adding an annual payment option as an alternative to the 10-year fee, the organization was met with criticism charging that for physicians who did not enroll in and pay for the program in years in which they did not have to complete any requirements, they became labeled not certified as a result of this change. According to a blog post from Richard Baron, MD, the president and CEO of ABIM, “This policy had a particular adverse effect on those who just completed training or were engaged in fellowship. That did not seem right to me, to our board, or to many other members of the internal medicine community.” The organization announced it now permits physicians who have met the other program requirements to keep their certification if they do not enroll in the MOC program during a particular year. Physicians will still need to be current with payments and meet ongoing program requirements, and internists must still meet five- and 10-year program milestones to maintain certification. The MOC program has come under fire over the past year for its requirements, fees, and content.

Source: ABIM news release, August 4, 2015.