ASH Clinical News July 2017 Bonus Issue | Page 4

Calendar ASH Consultative Hematology Course September 7, 2017 Chicago, IL (prior to the 2017 ASH Meeting on Hematologic Malignancies) December 11, 2017 Atlanta, GA (during the 2017 ASH Annual Meeting) An interactive, half-day program in which participants engage in case-based presentations and discussions focusing on non-malignant hematology topics such as thrombosis, thrombocytopenia, and bleeding. International Society of Experimental Hematology 46th Annual Scientific Meeting Peer Review Week September 11 – 17, 2017 Peer Review Week is an annual global event celebrating the essential role that peer review plays in maintaining scientific quality. The theme “Transparency in Review” will be explored in virtual events, such as webinars and social media activities, and in-person panel discussions that coincide with the Peer Review Congress in Chicago, Illinois. August 24 – 27, 2017 Frankfurt, Germany The ISEH 46th Annual Scientific Meeting features presenta- tions on cutting-edge, unpublished hematologic research. ASH Meeting on Hematologic Malignancies September 8 – 9, 2017 Chicago, IL Top experts in hematologic malignancies discuss the latest developments in clinical care and answer challenging patient care questions. Advanced Practice Providers Oncology Summit Chicago, IL The goal of this summit is to foster collaboration, share best practices, and provide a forum for peer-to-peer interaction among advanced practice providers who are actively engaged in caring for oncology patients. Upcoming Dates and Locations: September 15 – 16, 2017 Denver, CO ADYNOVATE [Antihemophilic Factor (Recombinant), PEGylated] Lyophilized Powder for Solution For Intravenous Injection Brief Summary of Prescribing Information: Please see package insert for full Prescribing Information. ® INDICATIONS AND USAGE ADYNOVATE, Antihemophilic Factor (Recombinant), PEGylated, is a human antihemophilic factor indicated in children and adults with hemophilia A (congenital factor VIII deficiency) for: • On-demand treatment and control of bleeding episodes • Perioperative management • Routine prophylaxis to reduce the frequency of bleeding episodes Limitation of Use ADYNOVATE is not indicated for the treatment of von Willebrand disease. CONTRAINDICATIONS ADYNOVATE is contraindicated in patients who have had prior anaphylactic reaction to ADYNOVATE, to the parent molecule ADVATE ® (Antihemophilic Factor [Recombinant]), mouse or hamster protein, or excipients of ADYNOVATE (e.g. Tris, mannitol, trehalose, glutathione, and/or polysorbate 80). WARNINGS AND PRECAUTIONS Hypersensitivity Reactions Hypersensitivity reactions are possible with ADYNOVATE. Allergic-type hypersensitivity reactions, including anaphylaxis, have been reported with other recombinant antihemophilic factor VIII products, including the parent molecule, ADVATE. Early signs of hypersensitivity reactions that can progress to anaphylaxis may include angioedema, chest tightness, dyspnea, wheezing, urticaria, and pruritus. Immediately discontinue administration and initiate appropriate treatment if hypersensitivity reactions occur. Neutralizing Antibodies Formation of neutralizing antibodies (inhibitors) to factor VIII can occur following administration of ADYNOVATE. Monitor patients regularly for the development of factor VIII inhibitors by appropriate clinical observations and laboratory tests. Perform an assay that measures factor VIII inhibitor concentration if the plasma factor VIII level fails to increase as expected, or if bleeding is not controlled with expected dose. Monitoring Laboratory Tests • Monitor plasma factor VIII activity by performing a validated one-stage clotting assay to confirm the adequate factor VIII levels have been achieved and maintained. • Monitor for the development of factor VIII inhibitors. Perform the Bethesda inhibitor assay to determine if factor VIII inhibitor is present. If expected factor VIII activity plasma levels are not attained, or if bleeding is not controlled with the expected dose of ADYNOVATE, use Bethesda Units (BU) to determine inhibitor levels. ADVERSE REACTIONS The most common adverse reactions (≥1% of subjects) reported in the clinical studies were headache and nausea. Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in clinical trials of another drug and may not reflect the rates observed in practice. The safety of ADYNOVATE was evaluated in 237 previously treated patients (PTPs) and 6 previously untreated patients (PUPs) with severe hemophilia A (factor VIII less than 1% of normal), who received at least one dose of ADYNOVATE in 3 completed multicenter, prospective, open label clinical studies and 4 ongoing clinical studies. The median duration of participation per subject was 401 (min-max: 3-1034) days and the median number of exposure days to ADYNOVATE per subject was 111 (min-max: 1-322). Table 1 lists the adverse reactions reported during clinical studies. October 13 – 14, 2017 Portland, OR Table 1: Adverse Reactions Reported for ADYNOVATE MedDRA System Organ Class Gastrointestinal Disorders Immune System Disorder Nervous System Disorders Skin and Subcutaneous Tissue Disorders Vascular Disorders Diarrhea Nausea Number of Subjects n (%) (N=234) 1 (0.4%) 2 (0.8%) Hypersensitivity a 1 (0.4%) 0.003 Headache 5 (2.1%) 0.026 Rash 1 (0.4%) 0.003 Flushing 1 (0.4%) 0.003 MedDRA Preferred Term Rate of AEs per 100 Infusions (N=30865) 0.003 0.006 a The event of hypersensitivity was a mild transient non-serious rash, occurring in one 2-year old patient who had developed a previous rash while on ADYNOVATE. Two cases of acute pancreatitis, with no precipitating cause identified in one case, were reported in adults during an extension study of the clinical trial which evaluated 137 subjects. Administration of ADYNOVATE continued and both cases resolved. Immunogenicity The risk of the development of factor VIII inhibitors with the use of ADYNOVATE was evaluated in 3 completed and 4 ongoing cl