The Walgreens Pipeline Report provides a summary … Walgreens Pipeline Report provides a summary of the specialty medications that may be approved by the FDA within the next few years

The Walgreens Pipeline Report provides a summary of the specialty medications that may be approved by the FDA within the next few years. While not all-inclusive, this report focuses on medications in Phase III studies that may impact treatment for certain specialty disease states or conditions. It also highlights select, recently approved or soon-to-be-approved specialty medications of interest

to the marketplace. Drug information for approved products should be reviewed using the PI (prescribing information). For full PI, please refer to the DailyMed website. The medications with an asterisk indicate they have a boxed warning.

Note: This report is not intended for use by patients.

1 PIPELINE REPORT | Third Quarter 2014

Medications to watch Here is a closer look at a few recently approved or soon-to-be-approved medications that may have a significant impact on therapeutic classes and treatment for specific disease states and conditions.

Pembrolizumab Pembrolizumab is a programmed cell death 1 (PD-1) checkpoint inhibitor which activates the immune system to target cancer cells. Merck is conducting an ongoing open-label, single-arm, phase Ib trial (KEYNOTE-001), evaluating pembrolizumab in 411 patients with advanced melanoma. In this trial, seven groups of patients with advanced melanoma were enrolled, including patients with varying stages of disease and those that had received previous therapies. Pembrolizumab is administered as an intravenous (IV) infusion with a proposed dose of 2 mg/kg once every three weeks. In KEYNOTE-001, the estimated overall survival (OS) rate at one year was 69 percent across all patient groups, with a rate of 74 percent in patients without prior Yervoy* (ipilimumab*) treatment and a rate of 65 percent in patients who progressed on or following Yervoy. At 18 months, the estimated OS was 62 percent. The median OS of the trial has not been reached yet. Two Phase III trials of pembrolizumab in melanoma are also ongoing.

Pembrolizumab has been granted breakthrough therapy designation. In May 2014, the FDA accepted the biologics license application (BLA) for pembrolizumab in the treatment of unresectable or metastatic melanoma in patients who have been previously treated with ipilimumab. The FDA granted priority review status to the application. A response to the BLA is expected in October 2014.

Panobinostat Novartis has filed a new drug application (NDA) for panobinostat in the treatment of relapsed or refractory multiple myeloma (MM). MM is a blood cancer that affects plasma cells with most people relapsing or becoming refractory to treatment. Panobinostat is an orally administered histone deacetylase inhibitor that inhibits cell growth and survival. *These medications have a boxed warning.

2014 Walgreen Co. All rights reserved.

PANORAMA-2 was an open-label, Phase II trial of panobinostat in combination with Velcade (bortezomib) and dexamethasone. Fifty-five patients with relapsed and bortezomib-refractory MM (progressed on or within 60 days of the last bortezomib-containing regimen) who had received at least two prior therapies including an immunomodulatory drug, Revlimid (lenalidomide) or Thalomid (thalidomide), were enrolled in the trial. Patients were treated in two phases, both with a two-week-on and one-week-off schedule. Phase one consisted of eight three-week cycles of panobinostat 20 mg by mouth three times per week, bortezomib 1.3 mg/m2 intravenous (IV) injection two times per week, and dexamethasone 20 mg by mouth four times per week on weeks 1 and 2. For patients who benefited from phase one, treatment continued in phase two with six-week cycles of panobinostat three times per week, bortezomib one time per week, and dexamethasone two times per week on weeks 1, 2, 4 and 5. The primary endpoint of the trial was overall response rate (ORR) after eight cycles of treatment. The ORR was 34.5 percent, leading the researchers to conclude that panobinostat, when combined with bortezomib and dexamethasone, can recapture responses in heavily pretreated, bortezomib-refractory MM patients. The most common side effects reported were diarrhea, fatigue, thrombocytopenia, nausea and anemia.

PANORAMA-1 was a randomized, double-blind, placebo-controlled, Phase III trial. In this trial, 768 patients with relapsed or relapsed and refractory MM who failed on at least one prior treatment were enrolled and randomized to receive treatment with panobinostat in combination with bortezomib and dexamethasone or bortezomib and dexamethasone alone. The same dosing schedule from PANORAMA-2 was used. The primary endpoint of this trial was progression-free survival (PFS). PFS was 12 months in the panobinostat group versus eight months in the placebo group which was considered statistically significant.

Panobinostat is designated as an orphan drug. The FDA accepted the NDA and granted priority review status to the application in May 2014.


Asfotase alfa Alexion Pharmaceuticals initiated a rolling BLA submission in April 2014 for asfotase alfa for the treatment of hypophosphatasia. Hypophosphatasia is an ultra-rare metabolic disease characterized by impaired phosphate and calcium regulation, leading to progressive damage to multiple vital organs including destruction and deformity of bones, profound muscle weakness, seizures, impaired renal function and respiratory failure. There are no approved treatments for hypophosphatasia. Asfotase alfa is a targeted enzyme replacement therapy designed to normalize the genetically defective metabolic process by targeting alkaline phosphatase directly to the deficient tissue.

Infants and young children with life-threatening or debilitating perinatal or infantile hypophosphatasia were enrolled in an open-label, Phase I/II trial. All patients received a single 2 mg/kg IV infusion of asfotase alfa, followed by 1 mg/kg subcutaneous injections three times per week. The subcutaneous dose could be increased up to 3 mg per kg if there were worsening failure to thrive, deteriorating pulmonary function or no radiographic evidence of skeletal improvement. The primary endpoint of the trial was the number of patients showing radiographic response after 24 weeks of treatment. Ten patients completed at least 24 weeks of treatment and substantial radiographic improvement in skeletal abnormalities was noted in all but one patient. The most common side effect reported was a subcutaneous injection site reaction.

Asfotase alfa is designated as an orphan drug with fast-track status. The FDA has also granted asfotase alfa breakthrough therapy designation. Alexion plans to complete the rolling BLA submission in the third quarter of 2014.



Medications recently approved Manufacturer/

Drug name Indication Mechanism of action/

Drug class Route of

administration Approval

date Comments

Bleeding disorders Biogen Idec/Eloctate (antihemophilic factor [recombinant], Fc fusion protein)

For the control and prevention of bleeding episodes, perioperative (surgical) management and routine prophylaxis in adults and children with hemophilia A

Promotes blood clotting/Factor replacement therapy

IV infusion 6/6/14 First hemophilia A therapy to extend the interval between prophylactic infusions

Novo Nordisk/NovoSeven RT* (coagulation factor VIIa [recombinant])

For the treatment of bleeding episodes and perioperative management in adults and children with Glanzmanns thrombasthenia with refractoriness to platelet transfusions, with or without antibodies to platelets


IV injection 7/7/14 Previously approved for the treatment of hemophilia A or B with inhibitors, acquired hemophilia, and congenital factor VII deficiency

Octapharma/Octagam 10% (immune globulin intravenous [human])

For the treatment of chronic immune thrombocytopenic purpura (ITP) in adults

Mechanism of action in ITP unknown/Immune globulin

IV infusion 7/17/14 Octagam 5% previously approved for treatment of primary humoral immunodeficiency

Hereditary angioedema Salix Pharmaceuticals and Pharming Group NV/Ruconest (C1 esterase inhibitor [recombinant])

For the treatment of acute attacks in adult and adolescent patients with hereditary angioedema (HAE)

Replaces deficient C1 esterase inhibitor/C1 esterase inhibitor replacement therapy

IV injection 7/16/14 First recombinant C1 esterase inhibitor therapy approved for HAE

Inflammatory diseases Takeda/Entyvio (vedolizumab) For the treatment of adults with moderately to

severely active ulcerative colitis (UC) and Crohns disease (CD) in patients who have had an inadequate response with, lost response to, or were intolerant to a tumor necrosis factor (TNF) blocker or immunomodulator, or had an inadequate response with, were intolerant to, or demonstrated dependence on corticosteroids

Modulates the inflammatory response/47 integrin inhibitor

IV infusion 5/20/14 First treatment for UC and CD designed specifically to target receptors in the gut

*These medications have a boxed warning.



Medications recently approved (continued) Manufacturer/


Drug class Oncology

Route of administration

Approvaldate Comments

Eli Lilly/Cyramza (ramucirumab)

As a single-agent for the treatment of patients with advanced or metastatic, gastric or gastro-esophageal junction adenocarcinoma with disease progression on or after prior fluoropyrimidine- or platinum-containing chemotherapy

Reduces tumor cell growth and blood supply/ Vascular endothelial growth factor receptor 2 (VEGFR2) antagonist

IV infusion 4/21/14 First FDA-approved treatment for this indication

Gilead Sciences/Zydelig (idelalisib)

In combination with rituximab, for the treatment of patients with relapsed chronic lymphocytic leukemia (CLL) for whom Rituxan* (rituximab) alone would be considered appropriate therapy due to other comorbidities For the treatment of patients with relapsed follicular B-cell non-Hodgkin lymphoma who have received at least two prior systemic therapies For the treatment of patients with relapsed small lymphocytic lymphoma who have received at least two prior systemic therapies

Inhibits cell growth and survival/ Phosphoinositide 3-kinase (PI3K) delta inhibitor

Oral 7/23/14 First-in-class PI3K delta inhibitor

GlaxoSmithKline and Genmab/Arzerra* (ofatumumab)

In combination with chlorambucil,* for the treatment of previously untreated patients with CLL for whom fludarabine*-based therapy is considered inappropriate

Targets the CD20 protein on malignant B-cells/Anti-CD20 antibody

IV infusion 4/17/14 Previously approved for the treatment of patients with CLL refractory to fludarabine* and alemtuzumab*

Janssen/Sylvant (siltuximab) For the treatment of patients with multicentric Castlemans disease (MCD) who are human immunodeficiency virus (HIV) negative and human herpesvirus-8 (HHV-8) negative

Interferes with the inflammatory response/ Interleukin (IL)-6 inhibitor

IV infusion 4/22/14 First FDA-approved treatment for this indication

Novartis/Zykadia (ceritinib) For the treatment of patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to Xalkori (crizotinib)

Inhibits cell growth and survival/ ALK inhibitor

Oral 4/29/14 First FDA-approved treatment for this indication

Spectrum Pharmaceuticals/ Beleodaq (belinostat)

For the treatment of patients with relapsed or refractory peripheral T-cell lymphoma

Inhibits cell growth and survival/Histone deacetylase inhibitor

IV infusion 7/3/14 Granted accelerated approval based on tumor response rate and duration of response; an improvement in survival or disease-related symptoms has not been established yet




Pipeline medications in Phase III trials Manufacturer/


Drug class Route of

administration Comments

Baxter/BAX 111 (recombinant von Willebrand factor)

For the treatment of bleeding in patients with von Willebrand disease

Bleeding disorders Promotes blood clotting/Factor replacement therapy

IV infusion Designated as an orphan drug Primary endpoint achieved in Phase III trial April 2014 BLA filing planned for 2014

Baxter/BAX 855 (recombinant factor VIII)

For the treatment and prevention of bleeding in patients with hemophilia A


IV infusion Completed enrollment of Phase III trial November 2013 Regulatory filings planned for late 2014

Baxter/OBI-1 (recombinant antihemophilic porcine sequence factor VIII)

For the treatment of bleeding in patients with acquired hemophilia A


IV infusion Designated as an orphan drug with fast-track status BLA filed December 2013

Vertex Pharmaceuticals/ Lumacaftor (VX-809)

NPS Pharmaceuticals/Natpara (recombinant human parathyroid hormone)

Merck/Corifollitropin alfa

Aeterna Zentaris/Macrilen (macimorelin acetate)

In combination with Kalydeco (ivacaftor) in patients with cystic fibrosis (CF) who have two copies of the F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene

For the treatment of hypoparathyroidism

For the development of multiple follicles and pregnancy in women participating in an assisted reproductive technology program

For the evaluation of adult growth hormone deficiency

Cystic fibrosis Increases the movement of CFTR to the cell surface/CFTR corrector

Endocrine disorders Replaces deficient hormone/ Hormone replacement therapy

Fertility Stimulates ovarian follicular growth/ Sustained follicle stimulant

Growth disorders Stimulates the secretion of growth hormone/Ghrelin receptor agonist

Oral

Subcutaneous injection


Oral

Designated as an orphan drug FDA granted breakthrough therapy designation NDA filing planned for fourth quarter 2014

Designated as an orphan drug BLA filed October 2013 A response to the BLA is expected October 2014

NDA accepted for standard review September 2013

Designated as an orphan drug NDA filed November 2013 A response to the NDA is expected November 2014



Pipeline medications in Phase III trials (continued) Manufacturer/


Drug class Route of


Hepatitis AbbVie/ABT-450 + ritonavir* ombitasvir (ABT-267) dasabuvir (ABT-333)

Bristol-Myers Squibb/Daclatasvir and asunaprevir

For the treatment of chronic HCV infection in genotype 1b patients

Prevents virus replication/NS5A inhibitor (daclatasvir), NS3 inhibitor (asunaprevir)

Oral

FDA granted breakthrough therapy designation NDA filed March 2014 FDA granted priority review status

A response to the NDA is expected November 2014

Bristol-Myers Squibb/Daclatasvir In combination with other agents for the treatment of chronic HCV infection

Prevents virus replication/NS5A inhibitor

Oral NDA filed March 2014

Gilead Sciences/Ledipasvir

Human immunodeficiency virus Gilead Sciences/Elvitegravir

Immune Response BioPharma/ Remune

Hypercholesterolemia Amgen/Evolocumab

Inflammatory diseases Novartis/Secukinumab (AIN457)

Sanofi and Regeneron Pharmaceuticals/Sarilumab

In combination with ribavirin for the treatment of chronic hepatitis C virus (HCV) infection in genotype 1 patients

In fixed-dose combination with Sovaldi (sofosbuvir) for the treatment of chronic HCV infection in genotype 1 patients

For the treatment of HIV infection in

treatment-experienced patients

To boost the immune system in HIV patients receiving antiviral treatment

For the treatment of hypercholesterolemia

For the treatment of plaque psoriasis

For the treatment of rheumatoid arthritis (RA)

Prevents virus replication/Protease inhibitor (ABT-450 + ritonavir), NS5A inhibitor (ABT-267), non-nucleoside polymerase inhibitor (ABT-333)

Prevents virus replication/NS5A inhibitor

Prevents virus replication/Integrase inhibitor

Induces an HIV-specific T-cell response/Therapeutic vaccine

Increases the removal of low-density lipoprotein cholesterol from the blood/Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor

Interferes with the inflammatory response/IL-17A inhibitor

Interferes with the inflammatory response/IL-16 inhibitor

Oral

Oral

Oral

Intramuscular (IM) injection




FDA granted breakthrough therapy designation NDA filed April 2014 FDA granted priority review status A response to the NDA is expected December 2014

FDA granted breakthrough therapy designation NDA filed February 2014 FDA granted priority review status A response to the NDA is expected October 2014

NDA filed June 2012 Received complete response letter April 2013 FDA accepted resubmission of NDA April 2014 A response to the NDA is expected October 2014

Designated as an orphan drug for pediatric patients Planning a new Phase II trial

Designated as an orphan drug for the treatment of homozygous familial hypercholesterolemia

Global regulatory filings planned for 2014

BLA filed October 2013 A response to the BLA is expected January 2015

Coprimary endpoints achieved in Phase III trial November 2013 Six phase III trials ongoing



-




Drug class Route of


Catalyst Pharmaceutical Partners/ Firdapse (amifampridine phosphate)

Amicus Therapeutics and GlaxoSmithKline/Amigal (migalastat HCl)

Lambert Eaton Myasthenic Syndrome For the treatment of symptoms associated with Lambert-Eaton myasthenic syndrome

Improves impulse conduction in nerve fibers/Potassium channel blocker

Lysosomal storage diseases For the treatment of Fabry disease Binds to and stabilizes alpha-

galactosidase/Alpha-galactosidase A enhancer

Oral

Oral

Designated as an orphan drug FDA granted breakthrough therapy designation Phase III results are expected third quarter 2014

Designated as an orphan drug Primary endpoint not achieved in stage I of first Phase III trial

December 2012 Primary endpoint achieved in stage II of first Phase III trial

April 2014 Top-line results from second Phase III trial are expected third

quarter 2014

Genzyme/Cerdelga (eliglustat) For the treatment of adult patients with Gaucher disease type 1

Reduces the production of glucosylceramide/Glucosylceramide synthase inhibitor

Oral Designated as an orphan drug NDA accepted and granted priority review December 2013

Synageva BioPharma/ Sebelipase alfa

Alexion Pharmaceuticals/ Asfotase alfa

Biogen Idec/Plegridy (peginterferon beta-1a)

For the treatment of early and late onset lysosomal acid lipase (LAL) deficiency

Replaces deficient LAL/Enzyme replacement therapy

Metabolic disorders For the treatment of hypophosphatasia Normalizes the genetically defective

metabolic process/Targeted enzyme replacement therapy

Multiple sclerosis For the treatment of relapsing-remitting multiple sclerosis (MS)

Unknown mechanism of action in MS/Interferon

IV infusion



Designated as an orphan drug with fast-track status FDA granted breakthrough therapy designation for early onset

LAL deficiency Top-line Phase III results are expected second half 2014

Designated as an orphan drug with fast-track status FDA granted breakthrough therapy designation Initiated rolling BLA submission April 2014

Dosed once every two or four weeks FDA granted fast-track status BLA accepted for standard review July 2013 FDA extended the BLA review period by three months

Teva Pharmaceuticals/Laquinimod For the treatment of relapsing-remitting MS

Inhibits autoimmune and inflammatory disease activity/ Immunomodulatory agent

Oral Third Phase III trial is ongoing, results are expected 2016 This trial is being conducted under a special protocol assessment





Drug class Route of


Muscular dystrophy Prosensa Holding N.V./Drisapersen

Sarepta Therapeutics/Eteplirsen

AstraZeneca, MedImmune/ Lynparza (olaparib)

For the treatment of platinum sensitive relapsed ovarian cancer patients who have a breast cancer (BRCA) mutation

Inhibits cell growth and survival/Poly ADP-ribose polymerase (PARP) inhibitor

Oral

Designated as an orphan drug NDA accepted priority review April 2014 FDA advisory committee did not recommend accelerated approval June 2014

Phase III trial ongoing

Bristol-Myers Squibb/Opdivo (nivolumab)

For the third-line treatment of squamous cell NSCLC

Activates immune system to target cancer cells/PD-1 checkpoint inhibitor

IV injection

FDA granted fast-track status Initiated rolling BLA submission April 2014; expecting to complete the application by the end of 2014

CTI BioPharma/Opaxio (paclitaxel poliglumex)

Eisai/Lenvatinib

Eli Lilly/Necitumumab

Merck/Pembrolizumab (MK-3475) formerly lambrolizumab

Novartis and Array BioPharma/ Binimetinib

Novartis/Midostaurin

For the treatment of Duchenne muscular dystrophy (DMD)

For the treatment of DMD

For the treatment of ovarian cancer

For the treatment of radioiodine-refractory differentiated thyroid cancer

For the treatment of metastatic squamous NSCLC

For the treatment of patients with advanced melanoma who have been previously treated with Yervoy* (ipilimumab*) For the treatment of neuroblastoma RAS viral (v-ras) oncogene homolog (NRAS) mutant melanoma

For treatment of patients with FLT-3 mutated acute myeloid leukemia (AML)

Enables production of a functional dystrophin protein/Exon skipping therapy

Enables production of a functional dystrophin protein/Exon skipping therapy

Inhibits cell division/ Microtubule inhibitor

Inhibits cell growth and survival/ Tyrosine kinase inhibitor (TKI)

Reduces tumor cell growth and blood supply/Epidermal growth factor receptor inhibitor

Activates immune system to target cancer cells/ PD-1 checkpoint inhibitor

Inhibits cell growth and survival/ Mitogen-activated protein kinase (MEK) inhibitor

Inhibits cell growth and survival/ Signal transduction inhibitor


IV infusion

IV infusion

Oral

IV infusion

IV infusion

Oral

Oral

Designated as an orphan drug FDA granted breakthrough therapy designation NDA filing planned for 2014

Designated as an orphan drug with fast-track status NDA filing planned for 2014

Links paclitaxel to a biodegradable polyglutamate polymer that delivers more chemotherapy to tumor cells

Completed enrollment of Phase III trial January 2014

Designated as an orphan drug Primary endpoint achieved in Phase III trial February 2014 NDA filing planned for 2014

Primary endpoint achieved in Phase III trial Filing anticipated by the end of 2014

FDA granted breakthrough therapy designation BLA accepted for priority review May 2014 A response to the BLA is expected October 2014

Designated as an orphan drug Regulatory filings planned for 2015

Designated as an orphan drug Regulatory filings planned for 2015

Oncology






Drug class Route of


Oncology Novartis/Panobinostat In combination with Velcade

(bortezomib) and dexamethasone for the treatment of relapsed or refractory MM

Inhibits cell growth and survival/Histone deacetylase inhibitor

Oral Designated as an orphan drug NDA accepted and granted priority review May 2014

Pfizer/Palbociclib In combination with letrozole for the treatment of breast cancer

Prevents tumor cell progression/ Cyclin-dependent kinase inhibitor

Oral FDA granted breakthrough therapy designation Primary endpoint achieved in Phase II trial February 2014 Phase III trials ongoing NDA filing planned for third quarter 2014

Primary immunodeficiency Baxter and Halozyme/HyQvia (immune globulin with recombinant human hyaluronidase)

For the treatment of adult patients with primary immunodeficiency

Replaces deficient immunoglobulin/ Replacement therapy

Subcutaneous infusion

BLA filed July 2011 Received complete response letter August 2012 Amended BLA filed fourth quarter 2013 FDA extended the BLA review period by three months

Pulmonary fibrosis Boehringer Ingelheim/Nintedanib For the treatment of idiopathic

pulmonary fibrosis (IPF) Targets growth factors/TKI Oral Designated as an orphan drug with fast-track status

FDA granted breakthrough therapy designation NDA accepted and granted priority review status July 2014

InterMune/Pirfenidone For the treatment of IPF Suppresses fibrosis and inflammation/Anti-fibrotic agent

Oral Designated as an orphan drug with fast-track status FDA granted breakthrough therapy designation Received a complete response letter May 2010 Resubmitted NDA May 2014

Pulmonary hypertension Actelion/Selexipag For the treatment of pulmonary arterial

hypertension (PAH) Reduces vascular smooth muscle constriction/Prostacyclin receptor agonist

Oral Designated as an orphan drug Primary endpoint achieved in Phase III trial June 2014



New dosage forms in the pipeline

Manufacturer/Drug name Indication

Mechanism of action/ Drug class

Human immunodeficiency virus

Current route of administration

Investigational route of


abacavir,* lamivudine*) Viiv Healthcare/Trii (dolutegravir,

Biogen Idec and AbbVie/ Daclizumab HYP (high-yield process)

For the treatment of HIV

For the treatment of relapsing-remitting MS

nucleoside reverse transcriptase inhibitors Prevents virus replication/Integrase inhibitor,

Multiple sclerosis Binds to the CD25 receptor on T-cells/ Therapeutic antibody

Oral

IV infusion

Oral Singl


Primary endpoJune 2014

Previously marketed as Zenapax* for the prevention of acute kidney rejection

y IM injection

NDA filed October 2013 e-tablet regimen

int achieved in Phase III trial

Novartis/Signifor LAR (pasireotide long-acting release)

For the treatment of acromegaly

Neuroendocrine disorders Binds somatostatin receptors/Somatostatin analogue


IM injection Monthl Primary endpo

July 2013 Regulatory submissions planned for 2014

int achieved in Phase III trial

*These medications have a boxed warning. Dosage form is not available. Only investigational route of administration is available at this time.



New indications in pipeline Manufacturer/

Drug name Current indication Investigational

indication Mechanism of action/

Drug class Route of


Vertex Pharmaceuticals/ Kalydeco (ivacaftor)

For the treatment of CF in patients age 6 years and older who have one of the following mutations in the CFTR gene: G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, or S549R

Cystic fibrosis For the treatment of CF patients ages 18 and older who have the R117H mutation in the CFTR gene

Increases chloride ion transport across cell membranes/CFTR potentiator

Oral Supplemental new drug application (sNDA) filed June 2014

AbbVie/Humira* (adalimumab)

For the treatment of RA, polyarticular juvenile idiopathic arthritis, psoriatic arthritis (PsA), ankylosing spondylitis, CD, UC and psoriasis

Inflammatory diseases For the treatment of hidradenitis suppurativa

Targets TNF alpha, which is involved in the inflammatory process/TNF inhibitor


Results from Phase III trials are expected 2014

Celgene/Otezla (apremilast)

For the treatment of adult patients with active PsA

For the treatment of psoriasis Modulates the inflammatory response/ Phosphodiesterase 4 inhibitor

Oral NDA filed September 2013 A response to the NDA is expected

September 2014

Pfizer/Xeljanz* (tofacitinib)

Genzyme/Lemtrada (alemtuzumab)

Celgene/Revlimid* (lenalidomide)

For the treatment of RA

For the treatment of B-cell CLL

For the treatment of previously treated MM, myelodysplastic syndromes and relapsed or refractory mantle cell lymphoma

For the treatment of moderate-to-severe chronic plaque psoriasis

Interferes with the inflammatory and immune responses/Janus kinase (JAK) inhibitor

Multiple sclerosis For the treatment of relapsing MS

Binds to the CD52 antigen on B-cells and T-cells/Therapeutic antibody

Oncology For the treatment of newly diagnosed MM

Possesses immunomodulatory, anti-inflammatory and antiangiogenic properties/Thalidomide analogue

Oral

IV injection

Oral

sNDA filing planned for 2015

FDA granted fast-track status Supplemental biologics license application

(sBLA) filed June 2012 Received a complete response letter

December 2013 FDA accepted sBLA resubmission for review

May 2014 A response to the sBLA is expected fourth

quarter 2014 Marketed as Campath* for CLL indication

Primary endpoint achieved in Phase III trial July 2013

sNDA filed April 2014




New indications in pipeline (continued) Manufacturer/

Drug name

Eli Lilly/Cyramza

Current indication

In combination with chemotherapy for

Investigational indication

Oncology For the treatment of patients Reduces tumor ce

Mechanism of action/Drug class

ll growth and

Route of administration

IV infusion Pri

Comments

mary endpoint achieved in Phase III trial (ramucirumab) the second-line treatment of NSCLC with advanced or metastatic,

gastric or gastro-esophageal junction adenocarcinoma with disease progression on or after prior fluoropyrimidine- or platinum-containing chemotherapy

blood supply/VEGFR2 antagonist February 2014 First regulatory filing planned for second

half 2014

(bevacizumab) Genentech/Avastin*

colorectal cancer, non-squamous NSCLC, glioblastoma, and metastatic renal cell carcinoma (RCC)

For the treatment of metastatic chemotherapy for the treatment of women with persistent, recurrent or metastatic cervical cancer or recurrent platinum-resistant ovarian cancer

In combination with blood supply/Vascular endothelial growth factor (VEGF) inhibitor

Reduces tumor cell growth and IV infusion July 2014

A response to the sBLA for cervical cancer is expected October 2014, and for ovarian cancer November 2014

sBLAs accepted and granted priority review

GlaxoSmithKline/ Votrient* (pazopanib)

For the treatment of RCC and soft tissue sarcoma

For the treatment of advanced epithelial ovarian cancer

Inhibits cell growth and survival/TKI Oral Designated as an orphan drug Primary endpoint achieved in Phase III trial

June 2013 Overall survival analysis of the Phase III

trial does not support an overall positive benefit-risk for this indication

Incyte Corporation/ Jakafi (ruxolitinib)

For the treatment of patients with intermediate or high-risk myelofibrosis (MF), including primary MF, post-polycythemia vera MF and post-essential thrombocythemia MF

For the treatment of polycythemia vera

Inhibits the formation and development of blood cells/JAK inhibitor

Oral Designated as an orphan drug with fast-track status

Primary endpoint achieved in Phase III trial March 2014

sNDA filing planned for 2014

Ipsen/Somatuline Depot (lanreotide)

For the long-term treatment of acromegalic patients who have had an inadequate response to surgery/ radiotherapy, or for whom surgery/ radiotherapy is not an option

For the treatment of gastroenteropancreatic neuroendocrine tumors

Binds somatostatin receptors/Somatostatin analogue


sNDA filed July 2014

Medivation and Astellas Pharma/Xtandi (enzalutamide)

For the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) who have previously received docetaxel

For the treatment of patients with chemotherapy-nave mCRPC

Inhibits cell growth and survival/ Androgen receptor inhibitor

Oral sNDA filed March 2014 FDA granted priority review status A response to the sNDA is expected

September 2014



13 PIPELINE REPORT | Third Quarter 2014 New indications in pipeline (continued)

Manufacturer/ Drug name Current indication

Investigational indication

Mechanism of action/Drug class

Route of administration Comments

Ophthalmology Regeneron Pharmaceuticals/ Eylea (aflibercept)

For the treatment of neovascular (wet) age-related macular degeneration and macular edema following central retinal vein occlusion

For the treatment of diabetic macular edema (DME) and macular edema following branch retinal vein occlusion (BRVO)

Binds vascular endothelial growth factor and placental growth factor/ Antiangiogenesis inhibitor

Intravitreal injection

sBLA for DME accepted December 2013 and sBLA for macular edema following BRVO accepted February 2014

A response to the sBLA for DME is expected August 2014 and for macular edema following BRVO October 2014

New biosimilars in pipeline Manufacturer/

Drug name Reference

Manufacturer/Product Investigational indication Mechanism of action/

Drug class Route of


Oncology Sandoz/Filgrastim Amgen/Neupogen (filgrastim) To decrease the incidence of infection as

manifested by febrile neutropenia in patients with nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a significant incidence of severe neutropenia with fever

Stimulates production of neutrophils/Granulocyte colony-stimulating factor

Subcutaneous injection, IV infusion,

or subcutaneous infusion

BLA accepted July 2014


PIPELINE REPORT | Third Quarter 2014 14

Glossary of terms

BLA Stands for biologics license application, similar to an NDA but used for investigational medications that are considered to be biologic agents.

Breakthrough therapy designation Intended to expedite the development and review of a potential new drug for serious or life-threatening diseases.

Complete-response letter Issued to let the applicant know that the review period for an investigational agent is complete, and that the NDA or BLA is not yet ready for approval.

Double-blind trial A type of study in which the participants and the investigators are blinded to treatment. This type of study has less bias than nonblinded studies.

Fast track Designation granted by the FDA to an investigational agent indicating an expedited review of the NDA or BLA; usually applies to medications that treat serious or life-threatening conditions and demonstrate the potential to address unmet medical needs.

NDA Stands for new drug application, the process by which a manufacturer submits information to the FDA to gain approval for the agent; conducted after Phase III development is completed.

Orphan drug A medication that treats a rare disease that affects fewer than 200,000 Americans. A medication granted orphan drug status is entitled to seven years of marketing exclusivity.

Phase III Last phase of medication development; involves safety and efficacy trials of the new medication. This phase of development can take years to complete.



Glossary of terms (continued)

Priority review Designation granted by the FDA to an investigational agent after it has been submitted to the FDA for approval. A priority designation means that the FDA will review and take action on the application (approve or not approve) within six months instead of the standard 10 months for all other medication filings.

Rolling submission Usually applies to fast-track medications; indicates that the review process can be started even before the FDA receives all the information. However, the FDA requires all the information before a final decision about approval can be made.

sBLA Stands for supplemental biologics license application, similar to sNDA but used for already approved investigational medications that are considered to be biologic agents.

sNDA Stands for supplemental new drug application; the process by which a pharmaceutical company submits information to the FDA to gain approval for a new indication for an agent that has already been approved by the FDA.



References Articles:

Richardson PG, Schlossman RL, Alsina M, et al. PANORAMA 2: panobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory myeloma. Blood. 2013;122(14):2331-2337.

Whyte MP, Greenberg CR, Salman NJ, et al. Enzyme-replacement therapy in life-threatening hypophosphatasia. N Engl J Med. 2012;366:904-13.

Websites:

ClinicalTrialsclinicaltrials.gov

DailyMeddailymed.nlm.nih.gov

EvaluatePharmaevaluategroup.com

Manufacturers websites

U.S. Food and Drug Administrationfda.gov

Information in the report is current as of July 2014, and was accessed on July 24, 2014. This report is for educational purposes only and is not deemed as an endorsement by Walgreen Co., its subsidiaries or affiliates. Claims made in this report about the efficacy of medications or the results of studies have been made by the medication manufacturer, the FDA or another third party.

Brand drug names are trademarks of their respective owners.

2014 Walgreen Co. All rights reserved. 14WG0034 - 0814

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14WG0034_3Q2014_Specialty_Pipeline_Report.pdf14WG0034_3Q2014_Specialty_Pipeline_Report.2.pdf

For the control and prevent on of bleeding episodes per operat ve surgical management and rout ne prophylaxis n adults and chi dren w th hemophi a A: Promotes b ood c ott ngFactor rep acement therapy: IV infusion: 6614: Novo Nord skNovoSeven RT coagulat on factor VIIa recombinant: Promotes b ood c ott ngFactor rep acement therapy_2: IV in ection: 7714: For the treatment of chronic mmune thrombocytopenic purpura ITP in adults: Mechan sm of act on n ITP unknownImmune globul n: IV infusion_2: 71714: TakedaEntyvio vedolizumab: fill_10: IV infusion_3: 52014: First treatment for UC and CD des gned specif ca y to target receptors n the gut: Reduces tumor ce growth and b ood supp y Vascular endothel al growth factor receptor 2 VEGFR2 antagonist: IV infusion_4: 42114: Gi ead Sc encesZyde g idelalisib: Inhibits cell growth and survival Phosphoinos t de 3kinase PI3K de ta inhibitor: Ora: 72314: Firstinclass PI3K de ta inhibitor: GlaxoSm thK ne and GenmabArzerra ofatumumab: Targets the CD20 prote n on ma gnant Bce sAnt CD20 ant body: IV infusion_5: 41714: JanssenSy vant siltuximab: Interferes with the inflammatory response Interleukin IL6 nhibitor: IV infusion_6: 42214: First FDAapproved treatment for this indication: Novart sZykad a cer t nib: Inhibits cell growth and survival ALK nh b tor: Ora_2: 42914: First FDAapproved treatment for this indication_2: Spectrum Pharmaceut ca s Be eodaq be nostat: For the treatment of pat ents w th relapsed or refractory periphera Tce ymphoma: Inhibits cell growth and survivalHistone deacetylase nhibitor: IV infusion_7: 7314: Indication: For the treatment of bleeding n pat ents w th von W ebrand disease: Promotes b ood c ott ngFactor rep acement therapy_3: IV infusion_8: BaxterBAX 855 recomb nant factor VIII: For the treatment and prevent on of b eed ng in patients with hemophilia A: Promotes b ood c ott ngFactor rep acement therapy_4: IV infusion_9: For the treatment of b eed ng n pat ents w th acquired hemophi a A: Promotes b ood c ott ngFactor rep acement therapy_5: IV infusion_10: Des gnated as an orphan drug with fasttrack status BLA f ed December 2013: For the eva uat on of adult growth hormone def ciency: St mu ates the secret on of growth hormoneGhrel n receptor agonist: Ora_3: Indication_2: In combination with ribavirin for the treatment of chronic hepat t s C virus HCV infection in genotype 1 patients: Ora_4: Br sto Myers Squ bbDac atasvir and asunaprevir: For the treatment of chron c HCV nfect on in genotype 1b patients: Prevents v rus rep cat onNS5A inhibitor dac atasvir NS3 nh b tor asunaprevir: Ora_5: Br sto Myers Squ bbDac atasvir: Ora_6: NDA f ed March 2014: In fixeddose combinat on w th Sova d sofosbuv r for the treatment of chronic HCV nfect on n genotype 1 pat ents: Prevents v rus rep cat onNS5A inhibitor: Ora_7: For the treatment of HIV nfect on n treatmentexper enced pat ents: Prevents v rus rep cat onIntegrase inhibitor: Ora_8: Intramuscular IM nject on: To boost the mmune system n HIV pat ents receiving ant viral treatment: Induces an HIVspecif c Tce responseTherapeut c vacc ne: For the treatment of p aque psor as s: Interferes with the inflammatory responseIL17A nhibitor: Subcutaneous in ection: Sanof and Regeneron Pharmaceut ca sSar umab: For the treatment of rheumato d arthr t s RA: Interferes with the inflammatory responseIL16 nhibitor: Subcutaneous in ection_2: Indication_3: Cata yst Pharmaceut ca Partners Firdapse am fampr d ne phosphate Am cus Therapeut cs and GlaxoSm thK neAm ga m ga astat HC: For the treatment of Fabry d sease: Binds to and stab zes a pha galactos daseAlphagalactos dase A enhancer: Ora_9: GenzymeCerde ga e g ustat: For the treatment of adu t pat ents w th Gaucher disease type 1: Ora_10: Des gnated as an orphan drug NDA accepted and granted pr or ty rev ew December 2013: For the treatment of ear y and ate onset lysosomal acid lipase LAL deficiency: Rep aces def c ent LALEnzyme rep acement therapy: IV infusion_11: For the treatment of relaps ngrem tt ng mu p e sclerosis MS: Unknown mechan sm of act on n MSInterferon: Subcutaneous in ection_3: Teva Pharmaceut calsLaquinimod: For the treatment of relaps ngrem tt ng MS: Ora_11: Th rd Phase III tr al s ongoing results are expected 2016 Th s tr a s be ng conducted under a spec a protoco assessment: Indication_4: Prosensa Ho d ng NVDrisapersen: For the treatment of Duchenne muscu ar dystrophy DMD: Subcutaneous in ection_4: For the treatment of DMD: IV infusion_12: Des gnated as an orphan drug with fasttrack status NDA f ng p anned for 2014: AstraZeneca MedImmune Lynparza olapar b: For the treatment of platinum sensitive re apsed ovarian cancer pat ents who have a breast cancer BRCA mutat on: Inhibits cell growth and surviva Po y ADPribose po ymerase PARP inhibitor: Ora_12: Br sto Myers Squ bbOpd vo nivolumab: For the thirdline treatment of squamous ce NSCLC: IV in ection_2: CTI B oPharmaOpax o pac taxe pol glumex: For the treatment of ovar an cancer: Inhibits cell division Microtubu e nh b tor: IV infusion_13: Eisa Lenvat n b: For the treatment of rad o odine refractory d fferent ated thyro d cancer: Inhibits cell growth and survival Tyros ne k nase nh b tor TKI: Ora_13: El L yNec tumumab: For the treatment of metastat c squamous NSCLC: IV infusion_14: Pr mary endpo nt ach eved n Phase III tria Fi ng ant c pated by the end of 2014: MerckPembrol zumab MK3475 formerly ambrol zumab: IV infusion_15: Novart s and Array B oPharma Bin met n b: Ora_14: Des gnated as an orphan drug Regu atory f ngs p anned for 2015: Novart sM dostaur n: For treatment of pat ents w th FLT3 mutated acute mye o d eukemia AML: Inhibits cell growth and survival Signa transduct on nh b tor: Ora_15: Des gnated as an orphan drug Regu atory f ngs p anned for 2015_2: Indication_5: NovartisPanob nostat: Ora_16: Des gnated as an orphan drug NDA accepted and granted pr or ty rev ew May 2014: Pf zerPa boc c b: In combination with letrozole for the treatment of breast cancer: Prevents tumor ce progress on Cyc ndependent k nase nhibitor: Ora_17: For the treatment of d opath c pulmonary f bros s IPF: Targets growth factorsTKI: Ora_18: For the treatment of IPF: Suppresses f bros s and inflammationAnt fibrotic agent: Ora_19: For the treatment of pulmonary arter al hypertens on PAH: Ora_20: Des gnated as an orphan drug Pr mary endpo nt ach eved n Phase III trial June 2014: For the treatment of acromegaly: Binds somatostat n receptorsSomatostat n analogue: Subcutaneous in ection_5: IM in ection: For the treatment of CF pat ents ages 18 and older who have the R117H mutat on n the CFTR gene: Increases chloride ion transport across cel membranesCFTR potent ator: Ora_21: For the treatment of h draden t s suppurat va: Targets TNF a pha wh ch s nvo ved in the inflammatory processTNF inhibitor: Subcutaneous in ection_6: Ce geneOtez a aprem ast: For the treatment of adu t pat ents w th act ve PsA: For the treatment of psor as s: Modu ates the nf ammatory response Phosphod esterase 4 nh b tor: Ora_22: Pf zerXe anz tofacitinib: For the treatment of RA: For the treatment of moderateto severe chron c p aque psor asis: Ora_23: Ce geneRev m d lena dom de: For the treatment of new y diagnosed MM: Possesses mmunomodu atory ant inflammatory and antiangiogenic propert esThal dom de analogue: Ora_24: In combination with chemotherapy for the secondline treatment of NSCLC: Reduces tumor ce growth and blood supplyVEGFR2 antagonist: IV infusion_16: Pr mary endpo nt ach eved n Phase III tr al February 2014 First regu atory f ng p anned for second half 2014: GenentechAvast n bevac zumab: For the treatment of metastat c co orecta cancer nonsquamous NSCLC glioblastoma and metastat c rena ce carc noma RCC: Reduces tumor ce growth and blood supplyVascu ar endothe a growth factor VEGF nhibitor: IV infusion_17: GlaxoSm thK ne Votr ent pazopan b: For the treatment of RCC and soft tissue sarcoma: For the treatment of advanced epithel al ovar an cancer: Inhibits cell growth and survivalTKI: Ora_25: Incyte Corporation Jakaf ruxo n b: For the treatment of polycythem a vera: Inhibits the formation and development of blood cellsJAK inhibitor: Ora_26: IpsenSomatu ne Depot lanreotide: For the treatment of gastroenteropancreat c neuroendocr ne tumors: Binds somatostat n receptorsSomatostat n ana ogue: Subcutaneous in ection_7: sNDA f ed Ju y 2014: Med vat on and Aste as PharmaXtand enza utam de: For the treatment of pat ents w th chemotherapynave mCRPC: Inhibits cell growth and survival Androgen receptor nhibitor: Ora_27: For the treatment of neovascu ar wet agere ated macu ar degenerat on and macu ar edema following central retina vein occ us on: For the treatment of d abet c macu ar edema DME and macu ar edema fo ow ng branch ret na ve n occ us on BRVO: Binds vascu ar endothe a growth factor and placental growth factor Ant angiogenes s nhibitor: Intravitrea in ection: Investigational indication: AmgenNeupogen filgrastim: St mu ates product on of neutrophi sGranu ocyte co ony st mu at ng factor: Subcutaneous in ection IV infusion or subcutaneous infusion:

Documents

The Walgreens Pipeline Report provides a summary … Walgreens Pipeline Report provides a summary of the specialty medications that may be approved by the FDA within the next few years