ASH Clinical News July 2017 Bonus Issue | Page 17

CLINICAL NEWS

The National Heart , Lung , and Blood Institute ( NHLBI ) announced two new funding opportunities for late-stage , single- or multi-site , investigator-initiated clinical trials that address critical questions that fall within the mission of the NHLBI and require non-traditional clinical trial designs with the opportunity for statistical novelty and / or innovation .

The opportunities will support scientific research on rare diseases or therapeutics in which sample-size limitations present challenges for examining the statistical power of traditional randomized clinical trials , precision medicine trials , and late-stage implementation research . The specific funding opportunities are :

• Catalyzing Innovation in Late Phase Clinical Trial Design and Statistical Analysis Plans ( U34 ): Applications due October 19 , 2017

• Catalyzing Innovation in Late Phase Clinical Trial Design and Statistical Analysis Plans Resource Access ( X01 ): Applications due January 12 , 2018

Source : National Heart , Lung , and Blood Institute press release , May 18 , 2017 .

Direct-to-consumer ( DTC ) advertising became legal in the United States in 1997 but has been debated ever since , with some groups claiming that this type of marketing is designed to encourage patients to pressure their physicians into prescribing more expensive medications . Now , the American Medical Association ( AMA ) is reviewing a proposed resolution to back federal regulations and legislation that would require drug manufacturers to disclose prices in DTC advertising .

The resolution is supported by state medical societies from Connecticut , Maine , Massachusetts , New Hampshire , Rhode Island , and Vermont , and states that , “ Prescription rates of those medications advertised directly to consumers have increased by 34.2 percent , compared [ with ] a 5.1 percent increase in other pharmaceuticals [… and these drugs ] tend to be the newer and more expensive ones in their classes .” The resolution also cites 73 existing branded drugs whose prices have

increased by ≥75 percent since 2007 , as well as climbing prices for many recent U . S . Food and Drug Administration ( FDA ) -approved oncology drugs .

“ Advertising should be required to state the manufacturer ’ s suggested retail price of those drugs ,” according to the resolution . “ In a free enterprise system such as we have in the United States , the purchasing public should be educated .”

If the resolution is approved , AMA delegates would begin to advocate to federal agencies , including the FDA and the Federal Trade Commission , for potential regulation of drug advertisements .

Source : Forbes , June 8 , 2017 .

The AMA ’ s biannual practice survey shows that the proportion of physicians who have an ownership stake in their own practices fell to 47.1 percent in 2016 . The survey included 3,500 U . S . physicians who provide ≥20 hours of patient care per week and are not employed by the federal government . These rates have been declining in recent decades , from 76.1 percent in 1983 to 53.2 percent in 2012 and 50.8 percent in 2014 . The survey also found that hospital acquisitions of practices have stalled , with the number of physicians directly employed by hospitals or hospital-owned practices remaining steady from 2014 through 2016 , at 32.8 percent . This was up slightly from 29 percent in 2012 .

“ Despite challenges posed by a changing health-care landscape , most physicians ( 57.8 %) provide care to patients in small practices of ≤10 physicians ,” the report ’ s authors wrote . “ There were signs of a gradual shift toward larger practices : In 2016 , 13.8 percent of physicians were working in practices with ≥50 physicians , compared [ with ] 12.2 percent in 2012 .”

Hospital ownership appeared to be more prevalent in primary-care practices , as nearly 33 percent of primary-care physicians ( PCPs ) in single-specialty groups reported working for hospitals , compared with 16.5 percent of non-PCPs .

A slight majority of physicians ( 55.8 %) worked in practices owned by doctors in 2016 , with 69 percent working in singlespecialty practices and 36.7 percent working in multispecialty groups . Overall , singlespecialty groups declined from 45.5 percent in 2012 to 42.8 percent in 2016 . Multispecialty groups , however , increased from 22.1 percent in 2012 to 24.6 percent in 2016 .

Doctor demographics also influenced

— AMERICAN MEDICAL ASSOCIATION RESOLUTION

employment statistics . Older doctors were more likely to own their practices , whereas younger doctors were more likely to hold employed positions ( ownership ranged from 27.9 % at ≤40 years to 54.9 % at ≥55 years ), and male doctors were more likely to have an equity stake in their practices ( 52.2 %), compared with female physicians ( 36.6 %).

Sources : American Medical Association , “ Policy Research Perspectives : Updated Data on Physician Practice Arrangements : Physician Ownership Drops Below 50 Percent ,” May 31 , 2017 ; American Medical Association press release , May 31 , 2017 .

The FDA has accepted a new drug application ( NDA ) for CPX-351 – a liposomal formulation of cytarabine and daunorubicin encapsulated at a 5:1 molar ratio – for the treatment of acute myeloid leukemia ( AML ). The NDA incorporates data from five clinical trials , including a controlled , pivotal , phase III trial that enrolled 309 patients ( age range = 60-75 years ) from 39 U . S . and Canadian sites . Patients were randomized to receive CPX-351 ( 100 μ / m 2 on days 1 , 3 , and 5 ) or 7 + 3 ( control arm ; cytarabine 100 mg / m 2 daily for 7 days followed by daunorubicin 60 mg / m 2 on days 1 , 2 , and 3 ).

The results demonstrated that CPX-351 reduced the risk of death by 31 percent , compared with 7 + 3 in older adults with high-risk secondary AML . The median overall survival with CPX-351 was 9.56 months ( 95 % CI 6.60-11.86 ), compared with 5.95 months ( 95 % CI 4.99-7.75 ) with 7 + 3 ( hazard ratio [ HR ] = 0.69 ; p = 0.005 ).

Rates of grade 3-5 non-hematologic adverse events were similar between the CPX-351 and 7 + 3 cohorts , the most common of which were febrile neutropenia ( 68 % vs . 71 %), pneumonia ( 20 % vs . 15 %), hypoxia ( 13 % vs . 15 %), sepsis ( 9 % vs . 7 %), hypertension ( 10 % vs . 5 %), respiratory failure ( 7 % each ), fatigue ( 7 % vs . 6 %), bacteremia ( 10 % vs . 2 %), and decreased ejection fraction ( 5 % each ).

The FDA previously granted CPX- 351 breakthrough-therapy designation for patients with therapy-related AML or AML with myelodysplasia-related changes . The FDA also granted CPX-351 fast track status for the treatment of older patients with secondary AML .

Source : Jazz Pharmaceuticals press release , May 31 , 2017 .

The FDA ’ s Oncologic Drugs Advisory Committee ( ODAC ) voted 14-1 to recommend approval of an epoetin alfa biosimilar agent . If approved by the FDA , this would be the first erythropoiesisstimulating biosimilar agent .

ODAC ’ s decision was based on demonstrated efficacy compared with the reference product , and approval would apply to all of the FDA-approved indications for epoetin alfa , including :

• treatment of anemia resulting from :

° ° chronic kidney disease in patients on and not on dialysis

° ° zidovudine in HIV-infected patients

° ° the effects of concomitant myelosuppressive chemotherapy

• reduction of allogeneic red blood cell transfusions in patients undergoing elective , non-cardiac , nonvascular surgery

Pfizer , the manufacturer of the biosimilar agent under review , is in the midst of a legal battle with Amgen , the manufacturer of the reference product , which claims that Pfizer provided its marketing notice for the biosimilar too early . Based on agreed-upon stipulations , makers of biosimilar products must provide 180-day marketing notices after FDA approval . This case is set to begin in September . ●

Sources : Pfizer press release , May 25 , 2017 ; Pharma Times , May 26 , 2017 .