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Baloxavir marboxil (Xofluza™; baloxavir) is an oral cap-dependent endonuclease inhibitor that has been developed by Roche and Shionogi. The drug blocks influenza virus proliferation by inhibiting the initiation of mRNA synthesis. In February 2018, baloxavir received its first global approval in Japan for the treatment of influenza A or B virus infections. Phase III development is underway in the USA, EU and other countries for this indication. This article summarized the milestones in the development of baloxavir leading to this first global approval for influenza A or B virus infections.

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Intravenous andexanet alfa [coagulation factor Xa (recombinant), inactivated-zhzo; Andexxa®] is a first-in-class recombinant modified factor Xa protein that has been developed by Portola Pharmaceuticals as a universal antidote to reverse anticoagulant effects of direct or indirect factor Xa inhibitors. In May 2018, andexanet alfa received its first global approval in the USA for use in patients treated with rivaroxaban and apixaban, when reversal of anticoagulant effects is required in life-threatening or uncontrolled bleeding. Intravenous andexanet alfa is under regulatory review in the EU and is undergoing clinical development in Japan. This article summarizes the milestones in the development of andexanet alfa leading to this first global approval for reversing anticoagulation of rivaroxaban and apixaban in adults.

Pegaspargase (Oncaspar ® ), a pegylated form of native Escherichia coli -derived l -asparaginase (hereafter referred as E. coli l -asparaginase), is indicated in the USA and EU for the treatment of acute lymphoblastic leukaemia (ALL) as a component of multi-agent chemotherapy in paediatric and adult patients. Relative to E. coli l -asparaginase, pegaspargase has a prolonged circulation time, thereby offering less frequent administration. Moreover, pegylation of E. coli l -asparaginase may diminish the immunogenicity of the enzyme. Based on extensive evidence, intramuscular (IM) or intravenous (IV) administration of pegaspargase as a component of a multi-agent chemotherapy is an effective first-line treatment for paediatric and adult patients with ALL, as well as for the treatment of paediatric and adult patients with ALL and hypersensitivity to E. coli l -asparaginase. Pegaspargase had a manageable tolerability profile in paediatric and adult patients with newly diagnosed ALL, with the most commonly occurring adverse events being generally consistent to that seen with E. coli l -asparaginase. Pegaspargase treatment in patients with relapsed ALL and hypersensitivity to E. coli l -asparaginase had a similar tolerability profile to that observed in patients with newly diagnosed ALL. Given the potentially reduced immunogenicity and more convenient dosage regimen over E. coli l -asparaginase, pegaspargase remains an important and effective treatment option for paediatric and adult patients with ALL, including those with hypersensitivity to E. coli l -asparaginase. Electronic supplementary material The online version of this article (10.1007/s40265-019-01120-1) contains supplementary material, which is available to authorized users.

Imipenem/cilastatin/relebactam (Recarbrio™) is an intravenously administered combination of the carbapenem imipenem, the renal dehydropeptidase-I inhibitor cilastatin, and the novel β-lactamase inhibitor relebactam. Relebactam is a potent inhibitor of class A and class C β-lactamases, conferring imipenem activity against many imipenem-nonsusceptible strains. Imipenem/cilastatin/relebactam is approved in the USA and EU for the treatment of hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP) in adults and other gram-negative infections, including complicated urinary tract infections (cUTIs) [including pyelonephritis] and complicated intra-abdominal infections (cIAIs), in adults with limited or no alternative treatment options. In pivotal phase II and III trials, imipenem/cilastatin/relebactam was noninferior to piperacillin/tazobactam in patients with HABP/VABP and to imipenem/cilastatin in patients with cUTIs and cIAIs. It was also effective in imipenem-nonsusceptible infections. Imipenem/cilastatin/relebactam was generally well tolerated, with a safety profile consistent with that of imipenem/cilastatin. Available evidence indicates that imipenem/cilastatin/relebactam is an effective and generally well tolerated option for gram-negative infections in adults, including critically ill and/or high-risk patients, and a potential therapy for infections caused by carbapenem-resistant pathogens.

Regorafenib (Stivarga), a small molecule inhibitor of multiple kinases, is the first drug to be approved for the treatment of hepatocellular carcinoma (HCC) in patients who have progressed during or after sorafenib therapy. Its approval was based on the results of the randomized, double-blind, placebo-controlled, multinational, phase III RESORCE trial in patients with HCC who had progressed during sorafenib therapy. In RESORCE, regorafenib significantly prolonged overall survival (OS; primary endpoint), progression-free survival (PFS) and time to progression (TTP) compared with placebo, with the OS benefit appearing to be largely due to disease stabilization. Regorafenib had an acceptable tolerability profile. The most common treatment-related adverse events in the regorafenib group included hand-foot skin reaction, fatigue, diarrhoea and hypertension. No fatal hepatic failure was reported with regorafenib in patients with HCC in RESORCE. In conclusion, current evidence suggests that regorafenib is an important new targeted therapy option for the treatment of HCC patients who have progressed on sorafenib therapy.

A fixed-dose combination of the hepatitis C virus (HCV) NS5B polymerase inhibitor sofosbuvir, the HCV NS5A inhibitor velpatasvir and the HCV NS3/4A protease inhibitor voxilaprevir (sofosbuvir/velpatasvir/voxilaprevir; Vosevi) is approved in the EU for the treatment of chronic HCV genotype 1, 2, 3, 4, 5 or 6 infection in adults. In the phase III POLARIS trials, in patients who had HCV genotype 1-6 infection with or without compensated cirrhosis, overall rates of sustained virological response at 12 weeks post-treatment (SVR) with sofosbuvir/velpatasvir/voxilaprevir were high after 8 weeks of treatment in direct-acting antiviral (DAA)-naïve patients and 12 weeks of treatment in DAA-experienced patients. However, 8 weeks of sofosbuvir/velpatasvir/voxilaprevir was inferior to 12 weeks of sofosbuvir/velpatasvir in cirrhotic or non-cirrhotic DAA-naïve patients with HCV genotype 1, 2, 4, 5 or 6 infection and non-cirrhotic DAA-naïve patients with HCV genotype 3 infection, mostly due to an insufficient treatment period. Sofosbuvir/velpatasvir/voxilaprevir was generally well tolerated, with most adverse events being of mild or moderate intensity. The most common adverse events included headache, fatigue, nausea and diarrhoea. In conclusion, sofosbuvir/velpatasvir/voxilaprevir is an important and effective option for the treatment of HCV genotype 1-6 infection in adults, especially those who have previously failed a DAA therapy with or without an HCV NS5A inhibitor.