Specialty Pipeline Update

CLINICAL SOLUTIONS

Drug Insights > December 2015 Specialty Pipeline Update

™ → New Drug Information Bendeka (bendamustine): Teva received FDA approval for their intravenously administered oncology drug to Alecensa® (alectinib): The Food and Drug Administration treat chronic lymphocytic leukemia and indolent B-cell (FDA) approved Genentech’s orally administered non-Hodgkin lymphoma. ALK‑inhibitor for the treatment of metastatic, non‑small ™ The FDA approved Bristol-Myers cell lung cancer in patients that are intolerant or Empliciti (elotuzumab): Squibb and AbbVie’s treatment of multiple myeloma. unresponsive to Xalkori® (crizotinib). Empliciti is to be used in combination with Revlimid® Uptravi™ (selexipag): The FDA approved Actelion’s and dexamethasone in patients that have received Uptravi for the treatment of pulmonary arterial prior therapy. The drug is administered by intravenous hypertension (PAH). The drug is approved in World infusion. Health Organization (WHO) Group I PAH patients ™ Lilly received approval for to delay disease progression and reduce the risk of Portrazza (necitumumab): their intravenously administered fully human epidermal hospitalization. growth factor receptor (EGFR) monoclonal antibody. Kanuma™ (sebelipase alfa): Alexion received FDA Portrazza is used for the first-line treatment of locally approval for their enzyme replacement therapy. Kanuma advanced or metastatic squamous non-small cell is approved to treat lysosomal acid lipase deficiency. lung cancer. This condition can be seen shortly after birth or later ™ in life. Vonvendi [von Willebrand factor (VWF), recombinant]: The FDA approved Baxalta’s recombinant VWF for the Ninlaro™ (ixazomib): The FDA approved Millennium acute treatment of bleeding episodes. Pharmaceuticals and Takeda’s Ninlaro for the treatment of patients with multiple myeloma who have received at least one prior therapy. Ninlaro is a proteasome inhibitor that is orally administered and will compete against Velcade®.

Vistogard™ (uridine triacetate): Wellstat Therapeutics received FDA approval for Vistogard for patients at risk of serious toxicity following an overdose of the chemotherapy agent 5-fluorouracil (5-FU) and patients exhibiting symptoms of serious toxicity within 96 hours

of 5-FU administration. Wellstat submitted Vistogard While the information in this newsletter is from sources we believe to be reliable, we do not warrant as a separate new drug application from the original that the information in this document is free from error. Use it only as a guide. Statements regarding drugs or manufacturers are not intended as promotion; those statements should not be used to approval of Xuriden (uridine triacetate) for hereditary make assumptions about formulary status. Each trademarked drug name is the property of its orotic aciduria. respective owner. Drug Insights > Specialty Pipeline Update Page 2

→ New Indications → December News

Opdivo® (nivolumab): Bristol-Myers Squibb received a “A panel of outside advisers to the U.S. Food and complete response letter from the FDA for an expanded Drug Administration indicated that efficacy data from indication in the treatment of metastatic melanoma. BioMarin Pharmaceutical Inc on its experimental drug The FDA did not approve the drug for treating BRAF V600 for treating a muscle wastage disorder [drisapersen] was mutation positive metastatic melanoma; however it not persuasive enough to warrant approval. The FDA was approved earlier for the treatment of BRAF V600 panel did not officially vote on an approval of the drug, wild‑type melanoma. but 15 out of 17 members were of the opinion that the lack of statistical significance in BioMarin’s late-stage Keytruda® (pembrolizumab): The FDA approved Merck’s study weakened the findings from two earlier studies.”1 Keytruda as a first-line treatment for unresectable or metastatic melanoma and as a treatment for patients “BioMarin Pharmaceutical Inc. announced that the U.S. with ipilimumab (Yervoy®)-refractory melanoma. Food and Drug Administration (FDA) has notified the Keytruda is also approved for advanced (metastatic) Company that they had not yet completed their review non-small cell lung cancer. process and would be unable to take an action by the Prescription Drug User Fee Act (PDUFA) action date for Kyndrisa™ (drisapersen) of December 27, 2015, and anticipate taking action in early January 2016.”2

“Amgen Inc said it filed with U.S. health regulators seeking approval to sell its first biosimilar drug, which would be a less expensive alternative to AbbVie’s Humira®, the world’s top-selling prescription medicine. Amgen said its drug, ABP 501, has demonstrated clinical equivalence and comparable safety to Humira (adalimumab) in late stage clinical trials for rheumatoid arthritis and the skin condition plaque psoriasis.”3 Drug Insights > Specialty Pipeline Update Page 3

Specialty New Product Approvals in the Past Twelve Months Route of Generic Name Brand Name Manufacturer Indication(s) Administration Date Approved selexipag Uptravi™ Actelion Pulmonary arterial hypertension Oral December 2015 von Willebrand factor, Vonvendi™ Baxalta Von Willebrand disease Intravenous December 2015 recombinant infusion sebelipase alfa Kanuma™ Alexion/Synageva Enzyme replacement therapy Intravenous December 2015 infusion asfotase alfa Strensiq™ Alexion Enzyme replacement therapy Subcutaneous November 2015 injection Factor VIII, recombinant, Adynovate™ Baxalta Hemophilia A Intravenous November 2015 pegylated infusion mepolizumab Nucala™ GlaxoSmithKline Severe eosinophilic asthma Subcutaneous November 2015 injection elvitegravir/cobicistat/ Genvoya™ Gilead HIV Oral November 2015 emtricitabine/tenofovir alafenamide Factor X concentrate Coagadex™ BioProducts Laboratory Factor X deficiency Intravenous October 2015 infusion uridine triacetate Xuriden™ Wellstat Therapeutics Hereditary orotic aciduria Oral October 2015 Factor VIII, recombinant Nuwiq® Octapharma Hemophilia A Intravenous September 2015 infusion uridine triacetate Xuriden™ Wellstat Therapeutics Hereditary orotic aciduria Oral September 2015 dichlorphenamide Keveyis™ Taro Primary hyperkalemic and Oral August 2015 hypokalemic periodic paralysis evolocumab Repatha™ Amgen High cholesterol Subcutaneous August 2015 injection daclatasvir Daklinza™ BMS Hepatitis C (genotype 3) Oral July 2015 ombitasvir, paritaprevir, Technivie™ AbbVie Hepatitis C (genotype 4) Oral July 2015 ritonavir with ribavirin alirocumab Praluent™ Sanofi-Genzyme High cholesterol Subcutaneous July 2015 injection lumacaftor/ivacaftor Orkambi™ Vertex Cystic fibrosis Oral July 2015 coagulation factor IX Ixinity™ Emergent BioSolutions Hemophilia B Intravenous May 2015 (recombinant) infusion glatiramer Glatopa™ Sandoz Multiple sclerosis Subcutaneous April 2015 injection deferasirox Jadenu™ Novartis Chronic iron overload Oral April 2015 raltegravir/lamivudine Dutrebis™ Merck HIV Oral March 2015 cholic acid Cholbam™ Asklepion Bile acid synthesis disorders Oral March 2015 Pharmaceuticals filgrastim-sndz (biosimilar Zarxio™ Sandoz Neutropenia Intravenous March 2015 to Neupogen®) infusion darunavir/cobicistat Prezcobix™ Janssen HIV Oral February 2015 atazanavir/cobicistat Evotaz™ BMS HIV Oral February 2015 ferric pyrophosphate citrate Triferic™ Rockwell Medical Iron replacement Intravenous January 2015 infusion recombinant human Natpara™ NPS Pharmaceuticals Hypoparathyroidism Intravenous January 2015 parathyroid hormone infusion secukinumab Cosentyx™ Novartis Plaque psoriasis Subcutaneous January 2015 injection Drug Insights > Specialty Pipeline Update Page 4

New Indications for Approved Specialty Products

Generic Name Brand Name Manufacturer New Indication(s) Date Approved ambrisentan Letairis® Gilead Treatment of pulmonary arterial hypertension, October 2015 in combination with tadalafil adalimumab Humira® AbbVie Treatment of moderate to severe hidradenitis September 2015 suppurativa cysteamine Procysbi® Raptor Pediatric nephropathic cystinosis in patients August 2015 Pharmaceuticals ages 2 – 6 years old abobotulinumtoxinA Dysport® Ipsen Treatment of upper limb spasticity in adults July 2015

sirolimus Rapamune® Pfizer Treatment of lymphangioleiomyomatosis May 2015

aflibercept Eylea® Regeneron Diabetic retinopathy April 2015

onabotulinumtoxinA Botox® Allergan Treatment of upper limb spasticity in adults April 2015

ivacaftor Kalydeco™ Vertex For use in children 2 – 5 years old who have March 2015 one of 10 mutations in the cystic fibrosis transmembrane conductance regulator gene ranibizumab Lucentis® Roche Treatment of diabetic retinopathy in patients February 2015 with diabetic macular edema ivacaftor Kalydeco™ Vertex For patients with mutation R117H January 2015 Drug Insights > Specialty Pipeline Update Page 5

Oncology Product Approvals in the Past Twelve Months

Route of Generic Name Brand Name Manufacturer Indication(s) Administration Date Approved alectinib Alecensa® Genentech Non-small cell lung cancer Oral December 2015

elotuzumab Empliciti™ Bristol-Myers Squibb/ Multiple myeloma Intravenous December 2015 AbbVie infusion bendamustine Bendeka™ Teva Chronic lymphocytic leukemia Intravenous December 2015 and indolent B-cell non-Hodgkin infusion lymphoma necitumumab Portrazza™ Lilly Non-small cell lung cancer Intravenous November 2015 infusion ixazomib Ninlaro® Millennium Multiple myeloma Oral November 2015 Pharmaceuticals/ Takeda daratumumab Darzalex™ Janssen Multiple myeloma Intravenous November 2015 infusion osimertinib Tagrisso™ AstraZeneca Non-small cell lung cancer Oral November 2015

irinotecan liposome Onivyde™ Merrimack Pancreatic cancer Intravenous November 2015 injection Pharmaceuticals infusion trabectedin Yondelis® Janssen Soft tissue sarcoma Intravenous November 2015 infusion cobimetinib Cotellic™ Genentech Metastatic melanoma Oral November 2015

talimogene Imlygic™ Amgen Metastatic melanoma Injection October 2015 laherparepvec trifluridine/tipiracil Lonsurf™ Otsuka Colorectal cancer Orals September 2015

gefitinib Iressa® AstraZeneca Non-small cell lung cancer Oral July 2015

sonidegib Odomzo™ Novartis Basal cell carcinoma Oral July 2015

dinutuximab Unituxin™ United Therapeutics’ Neuroblastoma Intravenous March 2015 infusion panobinostat Farydak™ Novartis Multiple myeloma Oral February 2015

palbociclib Ibrance® Pfizer Breast cancer Oral February 2015

lenvatinib Lenvima™ Eisai Thyroid cancer Oral February 2015 Drug Insights > Specialty Pipeline Update Page 6

New Indications for Approved Oncology Drugs

Generic Name Brand Name Manufacturer New Indication Date Approved pembrolizumab Keytruda® Merck First-line treatment for unresectable or metastatic December 2015 melanoma and as a treatment for patients with ipilimumab (Yervoy®)-refractory melanoma nivolumab Opdivo™ Bristol-Myers Squibb Treatment of BRAF V600 wild-type melanoma. December 2015

ledipasvir/sofosbuvir Harvoni® Gilead For use in patients with genotype 4, 5 and 6 chronic November 2015 hepatitis C virus (HCV) infection and in patients co‑infected with HIV ipilimumab Yervoy® Bristol-Myers Squibb Adjuvant therapy for patients with stage III melanoma November 2015

nivolumab Opdivo™ Bristol-Myers Squibb To be used in combination with Yervoy® (ipilimumab) October 2015 for the treatment of patients with unresectable or metastatic melanoma and for the treatment of patients with metastatic nonsquamous, non-small-cell lung cancer (NSCLC) whose disease progressed during or after platinum-based chemotherapy brentuximab vedotin Adcetris® Seattle Genetics To treat patients at high risk of relapse immediately August 2015 after an autologous hematopoietic stem cell transplant (HSCT) to help prevent progression of the disease carfilzomib Kyprolis® Onyx/Amgen To be used in combination with lenalidomide and July 2015 dexamethasone for the treatment of patients with relapsed multiple myeloma who have received one to three prior lines of therapy. ramucirumab Cyramza® Eli Lilly For use as a second-line treatment option for April 2015 metastatic colorectal cancer nivolumab Opdivo™ Bristol-Myers Squibb Advanced non-small cell lung cancer (NSCLC) March 2015

ibrutinib Imbruvica® Johnson & Johnson Waldenström's macroglobulinemia February 2015

lenalidomide Revlimid® Celgene First-line treatment for multiple myeloma February 2015 Drug Insights > Specialty Pipeline Update Page 7

Pipeline Watch

Route of Anticipated Generic Name Brand Name Manufacturer Indication(s) Administration Approval Date* daclizumab high-yield Zinbryta™ Biogen/AbbVie Multiple sclerosis Subcutaneous December 2015 process injection albutrepenonacog alfa N/A CSL Behring Hemophilia B Intravenous December 2015 [coagulation Factor IX] infusion Recombinant Factor VIII Kovaltry™ Bayer Hemophilia A Intravenous December 2015 infusion drisapersen Kyndrisa™ BioMarin Duchenne muscular dystrophy Subcutaneous January 2016 injection grazoprevir/elbasvir NA Merck Hepatitis C Oral January 2016 (genotypes 1, 4 and 6) ixekizumab N/A Lilly Plaque psoriasis Subcutaneous January 2016 injection deutetrabenazine N/A Teva Huntington’s disease Oral February 2016

eteplirsen N/A Sarepta Therapeutics Duchenne muscular dystrophy Intravenous February 2016 infusion emtricitabine/ N/A Gilead HIV Oral March 2016 tenofovir alafenamide/ rilpivirine reslizumab Cinquil® Teva Severe eosinophilic asthma Subcutaneous 1Q2016 injection/ intravenous infusion defibrotide N/A Jazz Pharmaceuticals Hepatic veno-occlusive disease Intravenous March 2016 infusion emtricitabine/ N/A Gilead HIV Oral April 2016 tenofovir alafenamide octreotide Mycapssa™ Chiasma Acromegaly Oral April 2016

* Anticipated approval dates are predictions made by Prime Therapeutics based on industry information. Drug Insights > Specialty Pipeline Update Page 8

Specialty Watch List

Criteria for inclusion on the Watch List include: Drug is submitted to the FDA and is anticipated to have $1 billion or more in annual global sales. Other considerations include the potential to impact a preferred product strategy (medical or pharmacy benefit) or the potential to shift trend from one benefit to the other (medical or pharmacy).

Anticipated Net new impact Net new impact Brand (generic)/ Proposed Indication/ Approval Similar Products to PMPM* to PMPM* Manufacturer Route of Administration (PDUFA date) (by indication) Spend* Pharmacy benefit Medical benefit Uptravi™ (selexipag)/ Pulmonary arterial Approved Orenitram® $ – $$ $ – $$ None Actelion hypertension (PAH)/ 12/22/2015 PDE-5 inhibitors Oral and ERAs drisapersen/BioMarin Duchenne’s muscular January 2016 None $ – $$ $ – $$ None dystrophy (SC) eteplirsen/ Duchenne’s muscular 2/26/2016 None $ Sarepta Therapeutics dystrophy (IV) Obeticholic acid Primary biliary cirrhosis 5/29/2016 ursodiol $ – $$ (PBC); $ – $$ (PBC); None (PBC); off-label use $$$$ (NASH) $$$$ (NASH) for non-alcoholic steatohepatitis (NASH)

* Notations: $ < $0.08 per member per month (PMPM), $$ = $0.08 – $0.39 PMPM, $$$ = $0.40 – $0.79 PMPM, $$$$ > $0.80 PMPM

References 1 http://www.reuters.com/article/biomarin-pharma-fda-idUSL3N13J4W720151124#4ZSKoTCYEkWof6wj.97 2 http://investors.bmrn.com/releasedetail.cfm?ReleaseID=947587 3 http://www.reuters.com/article/us-amgen-biosimilars-idUSKBN0TE2QS20151125#PFkcADwGsU6ORfVm.97 03001857