ASH Clinical News April 2017 New | Page 10

CLINICAL NEWS

The biotechnology start-up Grail recently announced its plan to raise $ 1 billion in financing to create a liquid biopsy assay that could detect cancer earlier by measuring circulating nucleic acids in blood . The company said it started a clinical trial with 10,000 patients , but studies will require hundreds of thousands of patients to test the technology appropriately .

“ By enabling the early detection of cancer in asymptomatic individuals through a simple blood screen , we aim to massively decrease cancer mortality by detecting the disease at a curable stage ,” said Jay Flatley , chairman of the board of Grail . The company has already secured $ 100 in funding , with contributions coming from Jeff Bezos and Bill Gates , as well as others .

Sources : Forbes , January 5 , 2017 ; Illumina news release , January 5 , 2017 .

When purchased outside the country , many prescription medicines cost less than half of what they do in the United States , driving more Americans to look online to fill their prescriptions despite the legal and safety implications , according to a poll conducted by the Kaiser Family Foundation .

Eight percent of respondents said they or someone in their household imported a prescription drug at some point , a number that translates to about 19 million adults in the United States based on current census population estimates . This number is much higher than the rates reported in surveys conducted by the U . S . government , which suggested that the number was around 2 percent in 2011 . The Kaiser poll was conducted nationally and included 1,202 adults ranging from 20 to ≥80 years of age .

Although it is illegal for Americans to import prescription drugs , the law is not rigorously enforced . In 2015 , the U . S . Food and Drug Administration ( FDA ) implemented a rule that expanded the authority of government border

inspectors to destroy drugs imported for personal use at their point of entry .

Spokespeople for U . S . Customs and Border Protection claim that the internet has made it much easier for Americans to buy prescription drugs abroad , which commonly come from disreputable sources . The FDA cautions that many online pharmacies are not well regulated . A 2014 international investigative operation found that many packages of medications supposedly imported from Australia , Canada , New Zealand , and the United Kingdom actually contained drugs from other countries , including India , China , and Laos . The agency also stated that medications from online pharmacies could be expired , inferior in quality , or counterfeit .

Source : Kaiser Health News , January 20 , 2017 .

In response to requests from drug manufacturers that they be able to communicate supplementary data and information about a product ’ s “ offlabel ” uses in promotional materials , the FDA issued draft guidance addressing questions about how to appropriately communicate this type of information while remaining consistent with a product ’ s approved label .

Previously , the FDA stated that it does not consider this supplementary information to be consistent with labeling guidelines ; once the agency approves or clears a medical product , it requires that the label indicate conditions for use of the product and directions and information on how to use the product safely and effectively under those specific conditions . If a manufacturer makes claims about a product that have not been evaluated by the FDA , it is considered misbranding and the company may face repercussions .

The FDA ’ s current draft guidance makes several suggestions for appropriate off-label communication , including :

• disclosing why the additional data are contextually relevant ( including study type , objectives , product dosage / use regimen , control cohort , patient population , and more )

• divulging limitations related to the study design and methodology

• accurately characterizing and contextualizing relevant information about the product ( including unfavorable or inconsistent findings )

The guidance is open for public comment until April 19 , 2017 . Visit federalregister . gov for more information .

Sources : U . S . Food and Drug Administration press release , January 18 , 2017 ; Reuters , January 18 , 2017 .

The manufacturers of SL-401 , a targeted therapy directed at the interleukin-3 receptor CD123 , reported a third patient death in the ongoing phase II trial of patients with blastic plasmacytoid dendritic cell neoplasm ( BPDCN ) and acute myeloid leukemia ( AML ).

The previous two deaths ( one patient with AML and another with BPDCN ) were related to capillary leak syndrome ( CLS ) – a sometimes fatal and documented adverse event of SL-401 . Though the third patient developed CLS , it has not yet been determined whether CLS was the direct cause of death .

The study is ongoing , but the CLS events have been noted in filings with the Securities and Exchange Commission and the FDA , as well as in the study ’ s informed consent forms and other information provided to investigators . The manufacturers will continue to report data to the FDA .

Preliminary results of the multicenter trial were presented at the 2016 ASH Annual Meeting . Researchers reported

that among the 15 evaluable patients with BPDCN , 87 percent ( n = 13 ) responded to treatment with SL-401 . The overall response rate was 100 percent when SL-401 was used as frontline treatment ( n = 10 / 10 ) and 60 percent when it was used in the relapsed / refractory setting ( n = 3 / 5 ).

Source : Stemline Therapeutics , Inc ., news release , February 4 , 2017 .

The FDA granted priority review for inotuzumab ozogamicin , an anti-CD22 monoclonal antibody , for the treatment of adult patients with relapsed / refractory B-cell precursor acute lymphocytic leukemia ( ALL ).

The decision was based on results of the phase III INO-VATE 1022 trial comparing inotuzumab ozogamicin with standard-of-care chemotherapy in 326 patients with relapsed / refractory B-cell ALL . A total of 218 patients ( 61 % were < 55 years ; all were CD22-positive ) were selected for primary analysis : 109 patients received inotuzumab ozogamicin 1.8 mg / m 2 and 109 patients received physicians ’ choice of fludarabine plus cytarabine with granulocyte colonystimulating factor , high-dose cytarabine , or cytarabine plus mitoxantrone .

The risk of disease progression or death was reduced by 55 percent in patients treated with inotuzumab ozogamicin versus standard therapy ( hazard ratio [ HR ] = 0.45 ; 97.5 % CI 0.43-0.61 ; p < 0.001 ). Overall survival also improved with inotuzumab ozogamicin , although it was not statistically significant ( HR = 0.77 ; 97.5 % CI 0.58- 1.03 ; p = 0.04 ).

Inotuzumab ozogamicin led to a complete response ( CR ) or CR with incomplete platelet recovery rate of 80.7 percent , compared with 29.4 percent with chemotherapy ( p < 0.001 ).

AEs were assessed in all patients who received at least one dose of inotuzumab ozogamicin ( n = 139 ) or chemotherapy ( n = 120 ). The most common grade ≥3 AEs in both groups were cytopenias . Any-grade veno-occlusive liver disease occurred in 15 patients ( 13 were grade ≥3 ) in the inotuzumab ozogamicin group , compared with just one in the chemotherapy cohort . Two deaths were associated with veno-occlusive liver disease in the inotuzumab ozogamicin arm . ●