New Parenteral Drugs and
Biologicals 2008
A Review for Home and Ambulatory Care Practitioners
NHIA Annual Conference
March 1, 2009
Anna Nowobilski-Vasilios PharmD MBA FASHP BCNSP
1/90
“New Drugs” Memory Lane
60
50
40
30
20
10
0
2001 2002 2003 2004 2005 2006 2007 2008
FDA Approvals New Molecular Entities Biologicals Parenterals
Pharmacist’s Letter. New Drugs Approved by the FDA 2008.
2/90
New Drugs and Biologicals presentations, NHIA Annual Meetings, 2002-2008.
New Drug Approvals 2008
January (7): ciclesonide, rh-thrombin, July (1): gadoxetate
etravirine, somatropin, amoxicillin, August (3): clevidipine, tetrabenazine,
fosaprepitant romiplostim
February (4): niacin-simvastatin, September (2): granisetron patch,
rilonacept, desvenlafaxine, r- lobenguane sulfate I 123
antihemophilic factor October (6): silodosin, C1 inhibitor
March (2): levoleucovorin, (human), benzoyl peroxide &
bendamustine clindamycin topical, lacosamide,
April (6): rotavirus vaccine, mesalamine, fesoterodine
regadenoson, olopatadine, November (3): rufinamide,
sumatriptan-naproxen, certolizumab eltrombopag, tapentadol
pegol, methylnaltrexone bromide December (7): synthetic conjugated
May (2): alvimopan, r-Factor VIIa estrogen, adapalene & benzoyl
June (5): triamcinolone acetonide, DTP- peroxide, plerixafor, zolpidem
Polio-H.influenzae vaccine, tartrate, gadofosveset trisodium,
metformin-repaglinide, difluprednate, bimatroprost, degarelix
DTP-Polio vaccine
(47) New Approvals (6) New Biologicals (28%)
(21) New Molecular Entities (14) New Parenterals (67%)
Pharmacist’s Letter, New Drugs Approved by the FDA in 2008
Drug Information Online. www.drugs.com
3/90
Learning Objectives
• Highlight the pathophysiology and therapeutic goals for
each corresponding disease state.
• Discuss the indications and appropriate role of each new
agent.
• Describe the major adverse effects, contraindications,
and precautions for new agent.
• List issues relating to dosing, administration, and storage
for each new agent.
• Discuss patient education and monitoring interventions
that would lead to achievement of therapeutic goals.
4/90
Review of Systems 2008
SYSTEM DRUG
HEENT clevidipine for severe hypertension
Pulmonary certolizumab for Crohn’s disease **
Cardiac methylnaltrexone for opioid constipation **
lacosamide for partial onset seizures
GI C-1 inhibitor for prevention of angioedema attacks
GU somatropin for GHD &Turner Syndrome
OB-GYN Factor VII for bleeding disorders
Neurology r-Antihemophilic Factor for bleeding disorders
Musculoskeletal romiplostim for ITP
Rheum/Imm rilonacept for cryopyrin-associated syndromes
Endocrine bendamustine for CLL and NHL **
Hematology plerixafor for autologous stem cell transplantation
Oncology degarelix for prostate cancer
fosaprepitant for chemotherapy-induced NV
Derm levoleucovorin for MTX rescue **
Psych DTP-Polio vaccine
Other DTP-Polio-H.influenzae vaccine
Key: Infusion ~ Injection ** Anticipated in 2007 to be approved in 2008. 5/90
Pulmonology
Pulmonology
PAH News
6/90
Pulmonology News
News
• Epoprostenol
• Approved for long-term IV treatment of
primary pulmonary hypertension and
pulmonary hypertension associated with
scleroderma
• Lyophilized powder
• Stable 24hr RT when reconstituted with SWI
or NSS
• Other epoprostenol products require special
diluent and gel packs to maintain 24h stability
Drug Information On Line, www.drugs.com.
NOTE: this product is a generic formulation and has not been assigned a brand name. 7/90
Cardiology
Cardiology
Severe Hypertension
8/90
Cardiology – Severe HTN Approved 8/1/2008
clevidipine IV
CleviprexTM
• Dihydropyridine calcium channel blocker (emulsion)
• 2nd IV CCB w/ shorter t½ than nicardipine
• Urgent TX of hypertensive crisis
• In ICU, OR and ED
• Goal: reduce BP quickly and avoid hypotension leading to MI,
stoke, vision loss
• Other agents: nitroprusside, nicardipine, fenoldopam,
nitroglycerine, phentolamine, esmolol, labetolol,
hydralazine
• Safety profile similar to nitroglycerine, nitroprusside, and
nicardipine in 1964 patients undergoing cardiac surgery
• ADR’s: hypotension, reflex tachycardia
• Alternative to older agents for perioperative or acute
severe hypertension.
• Monitor: BP, HR during infusion and until VS stabilized
The Medical Letter 2008; 50(1295):73.
9/90
Cleviprex™ (clevidipine) [package insert]. Parsippany NJ: The Medicines Company; August 2008.
Gastroenterology
Gastroenterology
Crohn’s Disease
Opioid Constipation
10/90
Gastroenterology
Crohn’s Disease
• Pathophysiology
• Chronic transmural inflammatory bowel disease
• Leads to fibrosis and obstructive symptoms
• Can affect any part of the GIT from mouth to anus.
• Prevalence: 1M WW; M:F = 1.1-1.8:1
• Incidence of colonic Crohn’s disease has increased
over the last 50 years (northern climates)
• Morbidity & Mortality
• Diarrhea, fever, rectal bleeding malnutrition, intestinal
tract narrowing, obstructions, abscesses, cramping,
abdominal pain, fistulas
• No to 5-fold increased risk of death
Pharmacist's Letter/Prescriber's Letter 2008;24(6):240607.
FDA News. April 22, 2008.
11/90
E-Medicine. www.emedicine.medscape.com. July 18, 2007.
Gastroenterology
Crohn’s Disease
• Treatment Options
• Aminosalicylates (mesalamine, sulfasalazine)
• Corticosteroids (prednisone)
• Immunomodulators (azathioprine, 6-MP,
methotrexate, cyclosporine)
• TNF blockers (infliximab, adalimumab … and …
certolizumab)
• Other: natalizumab
• Goals
• Achieve/maintain remission
• Improve QOL
• Minimize toxicity and complications
Pharmacist's Letter/Prescriber's Letter 2008;24(6):240607.
FDA News. April 22, 2008.
12/90
E-Medicine. www.emedicine.medscape.com. July 18, 2007.
Gastroenterology – Crohn’s Disease Approved 4/22/2008
certolizumab pegol SQ
Cimzia®
• Moderate to severe Crohn’s disease
• MOA: TNF blocker
• Humanized
• First pegylated TNF blocker
• Blocks inflammatory cascade
• Unlike infliximab and adalimumab, doesn’t induce:
• Complement-activated cytotoxicity
• Antibody-dependent T-cell mediated cytotoxicity
• Apoptosis
• 2 injections q 4wks by healthcare provider
• Adalimumab self-injected q 2 wks
• Infliximab infused
Pharmacist's Letter/Prescriber's Letter 2008;24(6):240607.
FDA News, April 22, 2008.
The Medical Letter 2008; 60(1297):81-2.
13/90
Cimzia® (certolizumab pegol) [package insert]. Smyrna GA: UCB, Inc. April 2008.
Gastroenterology – Crohn’s Disease certolizumab pegol
Clinical Trials
• Dose-response study1
• 292 pts: certolizumab 100, 200, 400 mg vs placebo @ wk 0, 4, 8.
• Onset of effect 2 wks; Greater efficacy at 400 mg
• Clinical response seen in certolizumab vs placebo @ wk 2, 4, 8,
10.
• Wk 12 % w/ clinical response not stat different betw certolizumab
400mg & placebo.
• PRECiSE 1: DBRPC (Rochester MN)2
• 659 adult pts: certolizumab vs placebo x 24 weeks (wk 0, 2, 4 &
q4wks)
• Week 6: response 35% vs 27%; remission NSS
• Week 26: response 37% vs 27%; remission NSS
• Serious adverse effects: 10% vs 7%; antibody development 8%
• Remission rates not significantly higher with certolizumab
1. Schreiber S, Rugeerts P, Fedorak RN, et al. A randomized, placebo-controlled trial of certolizumab pegol
(CDP870) for treatment of Crohn’s disease. Gastroenterology 2005; 129(3):807-18.
2. Sandborn WJ, Feagan BG, Stoinov S, et al. Certolizumab pegol for the treatment of Crohn’s disease. NEJM
2007; 357(3):228-38. 14/90
Gastroenterology – Crohn’s Disease certolizumab pegol
Clinical Trials
• PRECiSE 2: DBRPC, treatment withdrawal
(Germany)
• 668 adult pts: certolizumab 400mg wk 0, 2, 4
• 428 responders (64%): certolizumab vs placebo wks 8 thru
24
• Week 26: response 63% vs 36%; remission 48% vs 29%
• Serious adverse effects: 3% vs 4 mo not studied
• Not a controlled substance
Pharmacist's Letter/Prescriber's Letter 2008;24(6):240608.
FDA News. April 24, 2008.
The Medical Letter 2008;50(1292):63.
Resistor® (methylnaltrexone) [package insert]. Philadelphia PA and Tarrytown NY: Wyeth Pharmaceuticals and
21/90
Progenics Pharmaceuticals; April 2008.
Gastroenterology – Opioid Constipation methylnaltrexone
Clinical Trials
• 2 RDBPC trials
• 287 patients over 4 months
• Advanced late-stage illness
• 2 days
• After methylnaltrexone
• Slightly higher rate of elimination than placebo
• 4hr post dose BM
• 62% 0.15mg/kg; 58% 0.3 mg/kg, 15% placebo
• Not studied in pediatrics
FDA News. April 24, 2008.
Thomas J, Karver S, Cooney GA, et al. Methylnaltrexone for opioid-induced constipation in advanced illness.
NEJM 2008;358(22):2332-43.
22/90
Gastroenterology – Opioid Constipation methylnaltrexone
Safety
ADRs Precautions
• Abdominal pain (29 vs 10%) • CI’d in mechanical GI
• Flatulence (13 vs 6%) obstructions
• Discontinue in severe diarrhea,
• Nausea (12 vs 5%) nausea, or abdominal pain
• Dizziness (7 vs 2%) • ½ dose in severe renal
• Diarrhea (6 vs 2%) impairment (CrCl 17 yo
• 50 mg BID, increased based on clinical response by 100mg/day
weekly up to 400mg/day
• ADR’s: vertigo, diplopia, NVD, fatigue, gait disturbance, HA,
dizziness, pruritus
• IV: short term replacement when PO is not feasible
• over 30-60 minutes diluted or undiluted
• IV daily dose equivalent to oral daily dose
• 200ml/20mL single-use vial; store at RT
• Compatible w/ NSS, D5W & LR x24h in PVC or glass at RT
• Additional ADR’s: injection site pain, irritation, erythema
Vimpat® (lacosamide) [package insert]. Smyrna GA: UCB, Inc. October 2008.
www.ClinicalTrials.gov 28/90
Neurology – Partial Onset Seizures lacosamide
Administration
• Max dose 300mg/day in severe renal impairment
(CrCl 12 yo
FDA News. February 27, 2008.
E-Medicine. www.emedicine.medscape.com.
Arcalyst™ (rilonacept) [package insert]. Tarrytown NY: Regeneron Pharmaceuticals, Inc. July 2008. 34/90
Rheumatology-Immunology - CAPS rilonacept
Clinical Trial
• Approval based on one mfr trial
• 47 pts
• Daily diary assessment (0-10) of 5 CAPS s/s:
joint pain, rash, feeling of fever/chills, eye
redness/pain, fatigue
• Relief of symptoms noted within several days
FDA News. February 27, 2008. 35/90
Rheumatology-Immunology - CAPS rilonacept
Safety
ADR’s Precautions
• Injection site reactions (48 vs • IL-1 blockade may interfere w/
13% immune response to infections
• URI (26 vs 4%) • Do not start in patients with
• Increased total cholesterol, active/chronic infection
HDL, LDL & TG’s. Consider • Do not co-administer with TNF
lipid-lowering therapy based antagonists
on CV risk & guidelines. • Rare hypersensitivity
DI’s • Administer all recommended
• Rilonacept may normalize vaccinations BEFORE initiation
CYP450 enzymes which have of rilonacept.
been suppressed by cytokines • Pregnancy Category C
during chronic inflammation. • S/E not established in peds 4yo
• abatacept (Orencia®)
• Approved 4/8/2008 for juvenile idiopathic
arthritis (JIA) in > 6 yo as monotherapy of in
combination with methotrexate.
Drug Information Online. www.drugs.com. 45/90
Endocrinology
Endocrinology
Growth Hormone Deficiency
46/90
Endocrinology – GHD Approved 1/23/2008
SQ
somatropin
AccretropinTM
• Pediatric Indications
• Growth failure due to inadequate secretion of
growth hormone
• 0.18 to 0.3 mg/kg divided into equal daily doses
given 6-7 times weekly SC
• Short stature due to Turner Syndrome prior to
epiphyses closure
• 0.36 mg/kg divided into equal daily doses given 6-
7 times weekly SC
• Yet another growth hormone product!
Drug Information Online. www.drugs.com.
Accretropin™ (somatropin) [prescribing information]. Winnipeg Canada: Cangene Corporation. March 2007. 47/90
Hematology
Hematology
Hemophilia
ITP
CLL/NHL
48/90
Hematology - Hemophilia Approved 5/9/2008
IV
r-Factor VIIa
NovoSeven® RT
• recombinant Factor VIIa
• Room temperature storage for up to 2 yrs
• Sucrose and l-methionine
• Original formulation 3 yrs at refrigeration
• No change in indications:
• Bleeding and prevention of surgical bleeding in hemophilia A or
B with antibodies that neutralized Factors VIII or IX
• Bleeding and prevention of surgical bleeding in congenital Factor
VII deficiency
• Prevention of surgical bleeding in acquired hemophilia
• ADR’s: fever bleeding, injection site reaction, joint
discomfort, headache, elevation/fall BP, nausea,
vomiting, pain, swelling, rash.
FDA News. May 9, 2008.
49/90
FDA/CBER. 2008 Biological License Applications. www.fda.gov
Hematology - Hemophilia Approved 2/21/2008
r-antihemophilic factor IV
Xyntha™
• Additional treatment option
• Plasma and albumin free
• Minimizing risk of infection
• Indicated for
• Control & prevention of bleeding in patients with
hemophilia A
• Surgical prophylaxis in patients with hemophilia A
• 2 of 89 patient developed factor VIII inhibitors
• Store refrigerated.
• RT storage ok for up to 3 months.
Xyntha™ (recombinant antihemophilic factor) [package insert]. Philadelphia PA: Wyeth Pharmaceuticals, 2008.
Drug Information Online. www.drugs.com.
50/90
Hematology
Immune Thrombocytopenic Purpura
• Pathophysiology
• Immunological destruction of platelets with bone marrow inability
to compensate for loss
• Abnormal IgG binds to circulating platelets
• Prevalence
• 140,000
• Morbidity & Mortality
• Bruising & risk of life-threatening bleeding
• Treatment Options
• Corticosteroids
• IVIG, IV RhIG, rituximab
• Cyclophosphamide, azathioprine, danazol
• Splenectomy
FDA News. August 22, 2008.
E-medicine. www.emedicine.medscape.com 51/90
Hematology - ITP Approved 8/22/2008
SQ
romiplostim
NplateTM
• Fc-peptide fusion protein produced by
recombinant DNA in E.coli
• MOA: increases platelet production by binding
and activating the TPO receptor
• Bone marrow platelet stimulant, increasing
production via TPO receptor
• Chronic ITP refractory to corticosteroids,
immunoglobulins, or splenectomy
• Use only in pts at risk for bleeding
• Do not use to normalize platelet count
FDA News. August 22, 2008.
Nplate™ (romiplostim) [package insert]. Thousand Oaks CA: Amgen, Inc. August 2008. 52/90
Hematology - ITP romiplostim
Clinical Trials
• Approval based on 2 randomized parallel trials
• 125 patients who had received one prior ITP
treatment
• Pts w/ spleen in one study, w/o in other
• 6 months of treatment
• Pts tx’d w/ romiplostim maintained higher
platelet counts than those on placebo
• Overall platelet response rate 88% non-
splenectomised on drug, 79% splenectomised
on drug, 14% non-spelenectomised on placebo
FDA News. August 22, 2008.
Kuter DJ, Bussel JB, Lyons RM, et al. Efficacy of romiplostim in patients with chronic immune thrombocytopenic
purpura: a double-blind randomised controlled trial. Lancet 2008; 371(9610):395. 53/90
Hematology - ITP romiplostim
Safety
ADRs Precautions
• arthralgia, dizziness, • CI’d in MDS, risk of acute
insomnia, myalgia, leukemia
extremity pain, abdominal • Fibrous deposits in bone
marrow
pain, shoulder pain,
dyspepsia, paresthesia • Possible platelet drop below
baseline with romiplostim d/c
DIs • Blood clots possible due to
• Ok to admin w/ excessive platelet increases
corticosteroids, danazol, • Pregnancy Category C
(registry)
azathioprine, IVIG. • D/C romiplostim or
• If platelet count > 50x109/L, breastfeeding
D/C these
• S&E not established in peds
• No formal studies • Adjust doses in geriatrics
cautiously
• No studies in renal or hepatic
impairment
FDA News. August 22, 2008.
Nplate™ (romiplostim) [package insert]. Thousand Oaks CA: Amgen, Inc. August 2008. 54/90
Hematology - ITP romiplostim
Administration
Storage & Prep Dosing
• 250 & 500 mcg single use vials • Initial 1mcg/kg SC QWK
• Lyophilized powder • Weekly adjustments by
• Protect from light 1mcg/kg to platelet count >
• Reconstitute 50x109/L
• 250 mcg vial w/ 0.72 mL SWI • Clinical trail median dose 2
• 500 mcg vial w/ 1.2 mL SWI
mcg/kg
• Final Conc = 500 mcg/mL • If platelet count > 200x109/L x
2 wks, reduce by 1mcg/kg
• Swirl ( 400x109/L,
• Use w/in 24 hrs of don’t dose. Assess weekly.
reconstitution (RT or refrig) Resume when platelet count 55yo • 5-year survival 63%
• Treatment options: • Improved survival over last
nucleoside analogues, 20 yrs
monoclonal antibodies, • Treatment options:
allogeneic stem cell combination chemotherapy
transplantation
E-medicine. www.emedicine.medscape.com 57/90
Hematology – CLL & NHL Approved 3/20/2008
IV
bendamustine
Treanda®
• Novel DNA-alkylating agent
• Used in EU for lymphoma for yrs
• FDA approved
• Chronic lymphocytic leukemia (CLL)
• Non-Hodgkin lymphoma (NHL) that has
progressed in 6 months of treatment with a
rituximab regimen (10/31/2008)
The Medical Letter 2008;50(1299):91.
FDA Press Release. March 20, 2008.
Treanda® (bendamustine) [package insert]. Frazer PA: Cephalon, Inc. 2008. 58/90
Hematology – CLL & NHL bendamustine
Clinical Trials
• Approval in CLL due to one unpublished study
• 305 pts previously untreated for CLL
• IV bendamustine vs PO chlorambucil (Leukeran®)
• chlorambucil not the best comparitor
• fludarabine (Fludara®) more effective
• fludarabine + rituximab (Rituxan®) +/- cyclophosphamide CLL
ORR 90%; CR 70%
CLL bendamustine chlorambucil
Overall response rate (ORR) 68% 39%
Complete response (CR) 30% 24%
Median progression-free survival 21.7 mo 9.3 mo
Median duration of remission 18.9 mo 6.1 mo
The Medical Letter 2008;50(1299):91.
FDA Press Release. March 20, 2008. . 59/90
Hematology – CLL & NHL bendamustine
Clinical Trials
• Unpublished study
• 31 pts w/ relapsed CLL
• bendamustine + rituximab: ORR 65%; CR 13%
• Approval in progressed NHL w/in 6 mos of
treatment w/ rituximab regimen
• ORR >70% follicular, low-grade transformed NHL
refractory to rituximab regimens
• ORR 92% relapsed follicular, low-grade, and mantle
cell NHL.
The Medical Letter 2008;50(1299):91. 60/90
Hematology – CLL & NHL bendamustine
Safety
ADR’s Precautions
• grade 3/4 neutropenia • CI’d in hypersensitivity to bendamustine
(43%) or mannitol
• grade 3/4 thrombocytopenia • Potential concern: secondary
(11%) malignancies
• Myelosuppression
• nausea & vomiting (20%,
grade 3/4 65yo
• Not studied • Not studied in renal or
hepatic impairment
FDA News. December 29, 2008.
Degarelix [package insert]. Parsippany NJ: Ferring Pharmaceuticals. 2008. 69/90
Oncology – Prostate Cancer degarelix
Administration
Storage & Prep Dosing
• 80 & 120mg vials • Initial: 240mg as
• Reconstitute w/ SWI 2x120mg deep SC
• 120mg – 3mL injections
• 80 mg – 4.2mL • Maintenance: 80mg
• Keep vial vertical & swirl deep SC q 28 days
gently (15 min) • Abdominal area that will
• Do not turn vial upside not be exposed to
down to withdraw pressure
• Do not shake Under investigation in …
• Use w/in 1 hr • Female infertility
• BPH
Degarelix [package insert]. Parsippany NJ: Ferring Pharmaceuticals. 2008.
www.ClinicalTrials.gov 70/90
Oncology - CINV Approved 1/25/2008
IV
fosaprepitant
Emend®
• Prodrug of aprepitant, rapidly converts when given IV
• Selective antagonist of substance P
• Indicated, in combo with other antiemetics for prevention of
acute & delayed NV associated with high and moderate
emetogenic chemotherapy
• 115 mg IV over 15 min can be substituted for 125mg PO aprepitant
30 min prior to chemo, on Day 1 only.
• Aprepitant is mild CYP3A4 inhibitor. Do not use with pimozide,
terfenadine, astemizole, cisapride. Caution with ketoconazole, itraconazole,
nefazodone, troleandomycin, clarithromycin, ritonavir, nelfinavir, diltiazem.
• Administration of aprepitant with warfarin results in clinically
decreased INR.
• Chronic use for NV not recommended.
Emend® (fosaprepitant) [prescribing information]. Whitehouse Station NJ: Merck & Co. January 2008. 71/90
Oncology – MTX Rescue Approved 3/72008
IV
levoleucovorin
FusilevTM
• Pharmacologically active enantiomer of
leucovorin
• Indicated after high-dose MTX in osteosarcoma
or inadvertent FA antagonist overdose
• 50mg freeze-dried powder (w/ mannitol)
• Reconstitute w/ 5.3 mL 0.9% NSS = 10mg/mL
• Infuse nmt 160mg/min because of Ca content
• ½ usual dose of racemic form
• Pregnancy Category C
• Not studied in > 65 yo
• Monitor sCr & MTX levels
Drug Information Online. www.drugs.com
72/90
Fusilev™ (levoleucovorin) [package insert]. Irvine CA: Spectrum Pharmaceuticals. 2008.
Oncology
New Indications 2008
• bevacizumab (Avastin®)
• previously approved for combination treatment metastatic colon
cancer
• Approved 2/22/2008 in combination with paclitaxel as first-line
treatment of HER2-negative metastatic breast cancer.
• pemetrexed (Alimta®)
• Approved in 2004 in combination with cisplatin for malignant
pleural mesothelioma and second-line treatment for metastatic
non-small cell lung cancer
• Approved 9/29/2008 in combination with cisplatin as first-line
treatment of metastatic nonsquamous non-small cell lung cancer
• imatinib (Gleevec®)
• Approved 12/22/2008 to slow the recurrence of post-surgery
aggressive gastrointestinal stromal tumors.
Drug Information Online. www.drugs.com
The Medical Letter 2008;50(1285):34.
73/90
Dermatology
Dermatology
New Indication
74/90
Dermatology
New Indications 2008
• adalimumab (Humira®)
• Previously approved for rheumatoid arthritis
and psoriatic arthritis
• Approved 1/18/2008 for moderate to severe
chronic plaque psoriasis
Drug Information Online. www.drugs.com 75/90
Infectious Disease
Infectious Disease
Vaccines
76/90
Infectious Disease - Immunizations
Centers for Disease Control and Prevention. www.cdc.gov/vaccines 77/90
Infectious Disease - Immunizations
New Vaccines for Babies
• Rotavirus Vaccine (Rotarix®)
• Oral, live-attenuated monovalet
• 3rd approved, 2nd available
• Prevent severe gastroenteritis in infants & children
• Rotavirus causes 60,000 hospitalizations and 37
deaths in US annually
• Requires one less dose than other vaccine, but
includes only one serotype.
• DTP-Polio (Kinrix™)
• Vaccine against diphtheria, tetanus, pertussis, and
poliomyelitis
• Similar protection to separate DTaP and IPV
• Protection against four diseases with one less shot
• DTP-Polio-H.influenzae (Pentacel®)
• Vaccine against diphtheria, tetanus, pertussis,
poliomyelitis, and Haemophilus influenza
• Given as a four-dose series, reducing number of
shots by seven
The Medical Letter 2008;50(1293):66.
FDA News. April 3, 2008.
Press Releases. June 23, 2008 and June 24, 2008. 78/90
Infectious Disease
New Indications 2008
• micafungin (Mycamine®)
• Previously approved for esophageal candidiasis and prophylaxis
of candida infections in BCT.
• Approved 1/23/2008 for disseminated candidiasis and candidemia
• human papilloma virus vaccine (Gardasil®)
• Approved in 2006 for prevention of cervical cancer caused by
HPV types 16 and 18
• Approved 9/12/2008 for the prevention of vaginal and vulvar
cancer caused by HPV types 16 and 18
• pegylated interferon & ribavirin (PegIntron® & Rebetol®)
• Approved 12/12/2008 for use in chronic hepatitis C in > 3yo
• Tdap (Boostrix®)
• Approved 12/4/2008 as a booster in adults
Drug Information Online. www.drugs.com
FDA/CBER. 2008 Biological License Applications. www.fda.gov
79/90
Pipeline Trends
80/90
FDA Drug Approval Process
• Drug application took longer to review during Q3
2008
• FDA focused on imaging agents
• EU focused on chronic conditions and general uses
• FDA missed deadlines on 20% of the159 new drug
application through 10/31/2008.
• FDA Hires
• 800 employees in 2008, training has taken time
• FDA plans to meet a 90% of its review deadlines in
2009 with the new hires
ASHP Daily Briefings. December 11, 2008. December 22, 2008. 81/90
FDA Drug Approval Process
• 21 new entities approved by FDA in 2008
• Up from 18 in 2007
• missed target review dates for at least 15 drugs
• staff given permission to miss review dates due to
personnel shortages
• Goal of reviewing 90% application on time will not be
met in 2008
• Drug review duration
• Standard: 10 months
• Priority: 6 months
ASHP Daily Briefings. December 11, 2008. December 22, 2008. 82/90
FDA Drug Approval Process
• Approval time trends
• 2006: 13.7 months
• 2005: 24 months
• 2004: 24.7 months
• Priority drugs: 6 months (2004-2006)
• New drug development trends
• Personalized & specialized drugs
• Plan for unique and expensive therapies for
small populations
• Increase in orphan drug approvals
Hoffman JM, Shah ND, Vermeulen LC, et al. Projecting future drug expenditures 2009. AJHP 2009: 66:237-57.
83/90
Pipeline Driven by Biologics
• Historical development of small molecules
• 60% of revenue growth from biologicals is
forecast by non-biotech companies
• Prospective competition by bio-similars
• Monoclonal antibodies will be the stronger driver
for growth
• By 2010, annual sales of biologicals will have
increased by $26 billion, while small molecules
will have increased by $13 billion.
Pharmaceutical Business Review. Biologics driving growth to 2010. June 22, 2006. 84/90
Financial Impact
• Increased OOP burden on consumers
• Average 2007 co-payments
• $10 – generics
• $26 – preferred drugs
• $46 – non-preferred drugs
• $75 – fourth tier drugs
• high-cost drugs and biologicals
• Limited impact on drug expenditure for hospitals
& clinics
• Narrow application of new products
• Know hospital population!
Hoffman JM, Shah ND, Vermeulen LC, et al. Projecting future drug expenditures 2009. AJHP 2009: 66:237-57.
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2009 Parenteral Drug Pipeline
Neurology
• Fingolimod (FTY720, PO), alemtuzumab (Campath®), and
rituximab (Rituxan®) are in late-phase clinical trail for multiple
sclerosis.
• Dirucotide (MBP8298), an IV treatment, is in Phase III clinical trial
for secondary progressive multiple sclerosis.
Endocrinology
• Denosumab (AMG162, NDA 12/20/08) for osteoporosis. (Q4-2009)
Hematology
• Ferumoxytol (FerahemeTM, NDA 2/19/08) approval is delayed.
FDA requests additional non-trial information for this IV iron
treatment for CKD-related iron deficiency anemia
• Ecallantide (DX-88, BLA 11/21/2008) for hereditary angioedema
(HAE) granted FDA priority review 11/21/2008.
Hoffman JM, Shah ND, Vermeulen LC, et al. Projecting future drug expenditures 2009. AJHP 2009: 66:237-57.
ASHP Daily Briefings (published daily).
Drug Information Online. www.drugs.com.
www.ClinicalTrials.gov 86/90
2009 Parenteral Drug Pipeline
Oncology
• Casopitant (Rezonic™) for CINV (Q-3 2009)
• Glucarpidase (Voraxaze™) for MTX toxicity (Q4-
2009)
Dermatology
• Ustekinumab (CNTO1275, BLA 2/4/08) for
psoriasis. Approval declined 12/20. FDA wants
more information on mfr’s plan to inform physicians
and patients of potential risks. FDA advisory panel
unanimously recommended approval in June. (Q1-
2009)
Hoffman JM, Shah ND, Vermeulen LC, et al. Projecting future drug expenditures 2009. AJHP 2009: 66:237-57.
ASHP Daily Briefings (published daily).
Drug Information Online. www.drugs.com.
www.ClinicalTrials.gov 87/90
2009 Parenteral Drug Pipeline
Infectious Disease
• Dalbavancin (Zeven®) for resistant Gm(+) infections now
pushed back to 2010 due to FDA request for Phase III non-
inferiority trial.
• Telavancin (TD-6424, Arbelic™, NDA 12/06) once-daily for
skin and skin structure infections (Q1-2009)
• Ceftobiprole (BAL5788, Zeftera™, NDA 5/18/07), a new
injectable anti-MRSA cephalosporin for skin and skin structure
infections, did not receive FDA approval due to concerns
about a few sites used in its study. This could delay US
approval into 2010. Approved in Canada in 2008. (Q2-2009)
• Motavizumab (Numax®, BLA 1/30/08) for RSV prevention did
not receive FDA approval. FDA requests more information.
(Q4-2009)
Hoffman JM, Shah ND, Vermeulen LC, et al. Projecting future drug expenditures 2009. AJHP 2009: 66:237-57.
ASHP Daily Briefings (published daily).
Drug Information Online. www.drugs.com.
www.ClinicalTrials.gov 88/90
New Drug Approvals 2009
• Milnacipran (Savella™) approved 1/14/2009 for
fibromyalgia. (po)
• Human Fibrinogen Concentrate (RiaSTAP™)
approved 1/16/2009 for Congenital Fibrinogen
Deficiency.
• Antithrombin recombinant (ATryn®) approved
2/6/2009 for Antithrombin III Deficiency. First
transgenic therapeutic protein produced by
goats.
Stay tuned for
‘New Drugs VIII’ in 2010!
Drug Information Online. www.drugs.com. 89/90
Questions?
annanv@anovation.us
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