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CLINICAL NEWS

In December 2017 , CVS Health announced plans to purchase the health insurer Aetna for $ 69 billion , and according to a survey of decision-makers at 450 medium- and large-sized corporations , the move will affect employee health benefit decisions .

The survey found that 23 percent of respondents said it would accelerate a reassessment of health-care strategy at their corporations . Thirty-eight percent said they would delay reassessments until they could fully understand the merger transaction ’ s impact . The remaining 39 percent said they expected no change to their overall health-care strategy resulting from this merger .

The survey did not assess whether major employers expect the deal to change the cost of health benefits . However , 71 percent of respondents expect moderate changes to where and how employees access care , and 14 percent said they foresee significant changes .

“ This is on their radar screen in a bigger way than I would have anticipated ,” said Jim Winkler , senior vice president for health at Aon , the firm that conducted the survey . “ Typically , employers tend to look at this type of news and think , ‘ It ’ s too big , and it ’ s too far off to matter to me yet .’”

Among a smaller group of 210 respondents , 52 percent said they planned to keep pharmacy benefits separate from medical coverage , and an additional 15 percent said they are considering separating those contracts .

Source : Reuters , December 17 , 2017 .

The oral tyrosine kinase inhibitor bosutinib received expanded approval from the U . S . Food and Drug Administration ( FDA ) to treat adults with newly diagnosed Philadelphia chromosome-positive ( Ph +) chronic-phase ( CP ) chronic myeloid leukemia ( CML ).

The decision was based on results of the multinational , open-label , randomized , phase III BFORE ( Bosutinib trial in the First Line Chronic Myelogenous Leukemia Treatment ) study , which included 536 patients with Ph + CP-CML who were

randomized 1:1 to receive bosutinib 400 mg or imatinib 400 mg .

At 12 months , a higher percentage of patients receiving bosutinib achieved major molecular response ( 47.2 % vs . 36.9 %; p = 0.02 ). People treated with bosutinib also had a significantly higher rate of complete cytogenic response at 12 months ( 77.2 % vs . 66.4 %; p = 0.008 ).

The most common adverse events ( AEs ) associated with bosutinib included diarrhea ( 70 %), nausea ( 35 %), thrombocytopenia ( 35 %), rash ( 34 %), increased alanine aminotransferase ( 31 %), abdominal pain ( 25 %), and increased aspartate aminotransferase ( 23 %).

Bosutinib previously received FDA approval for adults with Ph + CML who were resistant or intolerant to prior therapy .

Source : Pfizer press release , December 19 , 2017 .

The FDA received a new drug application ( NDA ) for ivosidenib ( previously AG-120 ) for patients with relapsed / refractory IDH1- positive acute myeloid leukemia ( AML ).

The NDA was based on findings from an ongoing , single-arm , phase I trial , which was presented at the 2017 ASH Annual Meeting . A total of 258 patients ( 78 in the dose-escalation phase and 180 in the dose-expansion phase ) were treated with ivosidenib . As of May 12 , 2017 ( data cutoff ), 24 percent of patients ( n = 62 ) were continuing treatment , and the median duration of exposure was 3.5 months ( range = 0.1-33.5 months ). Twenty-two patients ( 8.5 %) discontinued treatment and went on to receive allogeneic hematopoietic cell transplantation .

The most common any-grade AEs ( occurring in ≥20 % of patients ) were diarrhea ( 33 %), leukocytosis ( 30 %), nausea ( 30 %), fatigue ( 29 %), febrile neutropenia ( 25 %), dyspnea ( 24 %), anemia ( 23 %), QT prolongation ( 23 %), peripheral edema ( 22 %), pyrexia ( 21 %), and decreased appetite ( 20 %). Twenty-nine participants ( 11.2 %) reported differentiation syndrome ( DS ), 14 ( 5.4 %) of which were grade ≥3 . Treatment was held because of DS in 11 patients ( 4.3 %), but no instances led to permanent treatment discontinuation or death . The most common cause of treatment discontinuation was disease progression , with 12.8 percent stopping treatment because of AEs .

Among 125 patients with relapsed /

refractory AML who received ivosidenib 500 mg for a minimum of six months ( 92 in dose-expansion and 33 in dose-escalation phases ), the rate of complete response ( CR ) or CR with partial hematologic recovery ( CRh ; primary endpoint ) was 30.4 percent , which lasted for a median duration of 8.2 months ( 95 % CI 5.5-12.0 ; range not provided ). The median duration of response was 6.5 months ( range not provided ). Of those who achieved CR , 28 percent were minimal residual disease – negative .

After 14.8 months of follow-up , the median overall survival ( OS ) was 8.8 months ( 95 % CI 6.7-10.2 ); the median OS was not reached in those achieving a CR / CRh and was 9.3 months for nonresponders .

Sources : Agios press release , December 26 , 2017 ; DiNardo CD , De Botton S , Stein EM , et al . Ivosidenib ( AG-120 ) in mutant IDH1 AML and advanced hematologic malignancies : results of a phase 1 dose escalation and expansion study . Abstract # 725 . Presented at the 2017 American Society of Hematology Annual Meeting , December 11 , 2017 ; Atlanta , GA .

The FDA updated the product label for nilotinib to include information on treatment discontinuation for certain patients . Nilotinib is approved for the treatment of Ph + CML . The updated label notes that patients with CP-CML who have received nilotinib for three or more years and whose leukemia has responded to treatment may be eligible to stop taking the drug .

The decision was based on two singlearm studies that assessed rate and duration of sustained treatment-free remission ( TFR ) after patients with CP-CML stopped taking nilotinib . The first trial included 190 newly diagnosed patients with CML who stopped treatment after three or more years ; 98 patients ( 51.6 %) were in TFR after 48 weeks and 93 ( 48.9 %) were in TFR after 96 weeks . The second trial included 126 patients who had switched from imatinib to nilotinib and had stopped taking nilotinib after three or more years ; 73 patients ( 57.9 %) were in TFR after 48 weeks and 67 ( 53.2 %) were in TFR after 96 weeks .

In both trials , researchers conducted regular and frequent monitoring of BCR- ABL protein levels . This monitoring is “ critical to the safe discontinuation of nilotinib , as this monitoring provides the first signs of relapse ,” according to the FDA .

Patients who discontinued nilotinib

reported musculoskeletal symptoms – such as body aches , bone pain , and pain in extremities – as the most common AEs . Some experienced prolonged musculoskeletal symptoms . The most common AEs associated with nilotinib include nausea , rash , headache , fatigue , pruritus , vomiting , diarrhea , cough , constipation , arthralgia , nasopharyngitis , pyrexia , night sweats , thrombocytopenia , myelosuppression , neutropenia , and anemia . Severe AEs include myelosuppression , cardiac and arterial vascular occlusive events , pancreatitis and elevated serum lipase , hepatotoxicity , abnormal levels of electrolytes in the blood , tumor lysis syndrome , hemorrhage , drug interactions with CYP3A4 inhibitors , gastrectomy , and fluid retention .

The drug carries a boxed warning for risk of QT prolongation and sudden death .

Nilotinib previously received priorityreview and orphan-drug designations .

Source : U . S . Food and Drug Administration press release , December 22 , 2017 .

The FDA extended by 90 days its review of the biologics license application ( BLA ) for andexanet alfa for the second time , from February 3 to May 4 , 2018 . The drug ’ s manufacturer , Portola Pharmaceuticals , Inc ., recently submitted additional data requested by the FDA for the ongoing ANNEXA-4 study , and the agency moved the action date to evaluate the new information .

Andexanet alfa is intended as a universal reversal agent for patients anticoagulated with an oral or injectable factor Xa inhibitor who experience a serious uncontrolled or life-threatening bleeding event or who require urgent or emergency surgery . The initial BLA is seeking approval for andexanet as a reversal agent for the anticoagulant effects of apixaban and rivaroxaban .

The company had first hoped to get approval of its agent in August 2016 , but the FDA issued a complete response letter seeking more information about Portola ’ s manufacturing , as well as additional data for inclusion of two other anticoagulants in the label , edoxaban and enoxaparin .

Andexanet alfa also is under review by the European Medicines Agency . A final decision by the European Commission on the marketing authorization application is anticipated in the first half of 2018 . ●

Source : Portola Pharmaceuticals , Inc ., news release , December 22 , 2017 .