HEALTHCARE SECTOR SECONDARY RESEARCH SAMPLE REPORT

HEALTHCARE SECTOR
SECONDARY RESEARCH
SAMPLE REPORT
Market Landscape Assessment:
Epidemiology, Current Treatments and
Unmet Needs, Clinical and Preclinical
Pipeline, Review of Key Trials,
Emerging Profile of New Therapies
Dan Meichenbaum
415.828.5265
dmeichenbaum@dectiva.com
Will Anlyan
347.334.2562
wanlyan@dectiva.com
1
Introduction of services
Market Research Intelligence:
Make More Informed Investment and Management Decisions
Dectiva specializes in delivering quantitative and qualitative market research data and analysis to leading
investment and business decision makers. By providing access to a a global panel of survey and interview
respondents, Dectiva empowers its clients with proprietary knowledge and timely insights in the life sciences
industry. Dectiva serves institutional investment, venture capital, private equity, and corporate entities.
Clients Use Dectiva's Primary Market Research Platform To:
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Survey targeted physician and patient groups to forecast demand and rate of adoption for new products
Test new target product profiles to investigate strengths, weaknesses, opportunities, and positioning relative to the competitive set
Identify unmet therapeutic needs and determine potential barriers to new product adoption
Analyze existing target markets to understand usage rates of competing products where sales information is incomplete
Collect early feedback from physicians, payers, and patients to inform new product design and development of target product profiles
Evaluate key drivers of market share to guide product enhancements and post-marketing efforts
Clients Use Dectiva's Secondary Market Research Services To Better Understand:
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Disease definition and epidemiology
Current treatments, market size by number of patients and sales volume, and unmet therapeutic needs
Clinical and preclinical pipelines
Status and results of key trials
Emerging profiles of competing new therapies
Pricing, coverage, and reimbursement issues
Clinical Trial Recruitment - Investigators and Patients:
Leveraging our global network, Dectiva performs custom recruitment campaigns of clinical investigators and patients for enrollment in clinical trials.
2
Secondary Research Detailed Overview
Secondary Research
Market Landscape Assessment
Extensive literature review:
» Scientific publications
» Trade journal and databases
» Securities analyst reports
» Government sponsored databases
» Syndicated databases
(based on client access)
Ideal for companies/investors exploring:
»New products in new areas
»New applications for existing products
Information distilled to deliver insights, as
well as data
Collect and analyze technical data on:
»Disease classification info
»Diagnostic algorithm
»Epidemiology
»Market drivers
»Competitive intelligence
(detailed pipeline and existing market overviews)
Completed within 5-7 days
Structured and customized reports to support business
planning and investment decisions
Completed within 3-5 days
3
Case Study - Overview
SECTOR
Life Sciences –
Thrombocytopenia
OBJECTIVES
ƒ Opportunity assessment
» Market size, growth
» Current treatments
» Unmet needs
ƒ Competitive landscape analysis
» Current treatments, advantages, limitations
» Pipeline competitors, trial design and potential positioning
ƒ Client Background
Pharmaceutical client evaluating multiple opportunities for in-licensing
Needed preliminary assessment of market attractiveness based on secondary data to
prioritize different opportunities
Next steps would be to conduct primary research to validate findings and to quantify value
of specific asset opportunity
ƒ Disease Area
Thrombocytopenia
Diverse patient population
Minimal syndicated market data available
4
Case Study - Table of Contents
Disease Definition and Epidemiology
Current Treatments and Unmet Needs
Clinical and Preclinical Pipeline
Key Trials
Conclusions
Emerging Profile of New Therapies
5
Disease Definition: Diverse Causes
•
Thrombocytopenia is a reduction in platelets (<100,000 platelets/µL), which can lead to excessive bleeding. The
condition is caused by:
– Suppression of megakaryocytes (responsible for platelet production) in the bone marrow.
– Immune disorders that produce antibodies that destroy platelets.
– Medications that result in myelosuppression and/or immunological destruction of platelets.
THROMBOCYTOPENIA CAUSES
Platelet Production
• Bone marrow diseases (leukemia, lymphoma,
MDS, multiple myeloma)
• Myelosuppressive therapies (e.g., chemotherapy,
radiation)
• Reduced thrombopoietin in the liver due to liver
disease (chronic hepatitis C, cirrhosis, liver
failure)
• Systemic viral or bacterial infection
– HIV, HCV, HCB
– Dengue fever infects megakaryocytes
• Sepsis
• Vitamin B12 or folic acid deficiency
• Numerous hereditary syndromes
Platelet Destruction
• Immune or idiopathic thrombocytopenic purpura
(ITP)
• Autoimmune disorders (e.g., lupus, rheumatoid
arthritis)
• Disseminated intravascular coagulopathy (DIC)
associated with cancer, sepsis or infection
• Medications: drug-antibody complexes bind and
activate platelets
– Heparin-induced thrombocytopenia is a
rare, but serious example of this
6
Epidemiology: 200,000+ US Cases Per Year
•
•
•
Medication induced thrombocytopenia has increased with introduction of new therapies that cause hematological
complications (e.g., antiinflammatories, cardiac & ulcer drugs, antibiotics).
Reduced thrombopoietin production in the liver results in thrombocytopenia in patients with chronic HCV infection and
liver disease.
Other forms of thrombocytopenia are more rare; congenital thrombocytopenia, though quite varied, accounts for <X%
of all cases.
US INCIDENCE OF THROMBOCYTOPENIA
Cause
Comments
Est. US 2008 Incidence
Annual Growth
ITP1
• Scientific references cite incidence of X/100,000 in adults and
X/1MM in children
• Non-scientific references cite X/1MM.
XXXXX
But may be as high as
XXXXX
+X%
Chemotherapy induced
thrombocytopenia2
• Based on Decision Resources estimates and projections
XXXXX
+X%
Heparin induced
thrombocytopenia (HIT)3
• XX% of patients treated with unfractionated heparin
• XX% develop HIT with thrombosis
• Estimates based only on cardiovascular patients
XXXXX
+X%
Myelodysplatic
syndromes (MDS)4
• MDS est 2008 incidence = XXXXX
• Thrombocytopenia occurs in ~XX% of patients
XXXXX
+X%
Chronic hepatitis C
infection5
• XX M Americans chronically infected
• XX% of chronic HCV patients affected
XXXXX
+X%
HIV/AIDS6
• XXXXX diagnosed cases of AIDS in US in 200X
• 1 yr incidence is XX% in patients with AIDS
XXXXX
+X%
Source: 1. ITP: Frederiksen H, Schmidt K, 1999; 2. Decision Resources, 2007; 3. HIT: Ohman EM, et al, 2005; 4. MDS: Ma X, et al, 2007 (est.
2003 MDS incidence rate of 3.56/100,000 applied to 2008 US population); Hagop K, et al, 2007; 5. HCV: Armstrong GL, et al, 2006; ChongShan W, et al, 2004; 6. HIV: CDC, HIV/AIDS Surveillance Report, 2005; Moore R, www.hopkins-hivguide.org
7
Current Treatment Approach:
Disrupt antibody-mediated destruction
•
•
•
ITP treatment guidelines established by American Society of Hematology (ASH) in 1996 are still in place today.
Following acute situations, many patients experience spontaneous remission.
Patients whose symptoms persist require further treatment; ~X% of patients become refractory.
ITP TREATMENT APPROACH
1st Line
Platelets >30,000/µL,
asymptomatic or minor
purpura
Dx
Platelets 20,00030,000/µL and/or
significant mucous
membrane bleeding
2nd Line / 3rd Line
Observation
Consider Splenectomy
Platelets <30,000/µL
after 4-6 weeks of
treatment
Cylcophosphamide /
Chemo Comb.
Drug Tx
Glucocorticoids
Rituximab Off-Label
Other Experimental Tx
Platelets <20,000/µL
and/or significant
mucous membrane
bleeding
Hospitalization & Drug
Tx
High dose IV glucocorticoids, IVIG, platelet transfusions
Source: George JN, et al, “ITP: A Practice Guideline Developed by Explicit Methods for the American Society of Hematology,” Blood, 1996
8
Current Treatment Approaches:
Treat Underlying Cause
•
In other forms of thrombocytopenia, physicians must assess underlying disease or risk-benefit of treatments causing
reduced platelet levels.
TREATMENT APPROACH FOR OTHER FORMS OF
THROMBOCYTOPENIA
Chemotherapy Induced
Thrombocytopenia
Platelet transfusion
Neumega (oprelvekin, IL-11)
Heparin Induced
Thrombocytopenia
Direct Thrombin Inhibitors
(argatroban, lepirudin)
Chronic Hepatitis C / Cirrhosis
Interferon Therapy
Liver Transplant
HIV
Antiretroviral Therapy
(AZT, ART)
9
Current Treatments:
Most Drugs are Immunomodulators
Prednisone
IV Gamma Globulin
(IVIG)
Rho(D) Immune
Glubulin (Anti-D)
Splenectomy
Neumega
(Oprelvekin)
Rituximab
MOA /
Rationale
• Prevents bleeding
• Raises platelet count
quickly
• Interrupts antibody
mediated platelet
destruction
• Approved for
prevention of Rh
immunization but also
shown to interrupt
platelet destruction
• Spleen is site for
antiplatelet antibody
production and
destruction of
opsonized platelets
• IL-11 enhances
growth and
maturation of IL-3
dependent
megakaryocytic
progenitors
• Eliminate Blymphocytes needed
for autoantibody
production
• May contribute to Fc
receptor blockade
Dosing /
Admin
• Begin 1mg/kg IV for 3
days; taper to <10-15
mg/d
• 1g/kg/d IV for 2 d
• 75µg/kg IM injection
• Surgical procedure
• 50µg/kg/d SC
injection
• 375mg/m2 four times
at weekly intervals
Duration of
Therapy
• 6 months
• Can be intermittent for
18 months
• Can be intermittent for
18 months
• N/A
• Given in 10 and 21
day courses
• TBD
Efficacy
• Platelet recovery
within 4 days vs 16
days in untreated
• Platelet increase in
75% of pts within 3-4
weeks
• 50% achieved normal
levels
• 68% response
• Transiently increases
platelet counts for 2-3
weeks
• 75-85% of patients
have initial response
• 25-40% relapse within
5-10 years
• 28-65% of patients
did not require
platelet transfusions,
vs 7-41% in placebo
arms
• 40-46% CRs
• 63% overall response
• 2-48 months duration
Safety
• Adverse events
associated with longterm steroid use
(hyperglycemia,
hypertension, weight
gain, growth
retardation)
• 15-75% of patients
have mild headache,
backache, nausea,
fever
• Some risk of aseptic
meningitis,
alloimmune
hemolysis
• Risk of alloimmune
hemolysis
• Potential for renal
failure
• Risks of infection
(lifelong use of
antibiotics
recommended by UK
guidelines but not US)
• Boxed warning for
allergic reactions
• Constitutional
toxicities, peri-pheral
edema
• Low incidence of
atrial arrhythmias and
syncope
• 22% mild/mod
adverse events
• 4% severe events
Source: George JN, et al, 1996; Cines DB, et al, “Congenital and Acquired Thrombocytopenia, Hematology, 2004; Beardsley DS, “ITP in the
21st Century,” Hematology, 2006; Panzer S, “New Therapeutic Options for Adult Chronic ITP, Vox Sanguinis, 2008
10
Unmet Needs: Safer Treatments and
Options for Refractory Cases
•
•
Current treatment options present risks of significant side effects and efficacy typically achieve 70% response rates or
less.
Even splenectomy, considered a “cure” for ITP, has efficacy of up to XX% but XX% may relapse within 5-10 years.
UNMET NEEDS
Safer therapies for patients at risk of bleeding or overt bleeding
tendency, to postpone splenectomy
Drugs with more rapid onset of action
Effective therapies for refractory patients
Drugs for patients scheduled for minor or major surgery, who can not
take steroids or IVIG
Diagnostics to more quickly and effectively identify patients with ITP
versus other conditions
Source: Panzer S, 2008; Decision Resources, “Managing the Side Effects of Chemotherapy,” 2007
11
Clinical Pipeline: Focus is on TPO receptor
•
•
•
•
•
•
Even when the cause of thrombocytopenia is platelet destruction, patients may also be subject to decreased platelet
production due to:
– Antiplatelet antibodies binding to megakaryocytes
– Apoptosis of megakaryocytes
– Low thrombopoietin (TPO) levels
1st generation TPO growth factors were recombinant megakaryocyte growth factors. These agents tended to be
immunogenic and were discontinued.
2nd generation agents are TPO peptide and non-peptide mimetics and TPO agonist antibodies. All bind to TPO
receptor but in different ways.
Potential concerns with new TPO agents are thrombosis, development of cancer/leukemia, antibody production,
marrow fibrosis and rebound effects when treatment is stopped.
Of the 11 clinical and 8 preclinical compounds in development for thrombocytopenia, at least 6 target the TPO
receptor.
Two compounds are awaiting FDA approval:
– Nplate (Romiplostim/AMG 531) and Promacta (Eltrombopag)
– Both will receive fast track or priority review, with launch expected by 20XX
12
Clinical Pipeline: Two Near-Term Entrants; Very Crowded Post-20XX
Discontinued
Discontinued
Mechanism
of Action
TPO
Receptor
MOA2
MOA3
MOA4
13
Clinical Pipeline
Source: Panzer S, 2008; ADIS R&D Insight; Amgen Press Release Jan 31, 2008
14
Clinical Pipeline
Source: Panzer S, 2008; ADIS R&D Insight; GSK Press Release Dec 10, 2007
15
Clinical Pipeline
•
•
Three additional TPO agonists are in clinical development – the XXX compounds are follow-up candidates to
Promacta.
Immunomodulators have also generated interest. CD20 antibodies affect the immune system’s ability to make
autoantibodies.
Drug
Developer
XXXXX
XXXXX
XXXXX
XXXXX
XXXXX
XXXXX
XXXXX
XXXXX
XXXXX
XXXXX
XXXXX
XXXXX
XXXXX
XXXXX
XXXXX
XXXXX
XXXXX
XXXXX
MOA
Phase
Indication
ROA
Thrombopoietin
receptor agonist
Thrombopoietin
receptor agonist
Syk tyrosine kinase
inhibitor
CD20 antigen
antagonist
CD20 antigen
antagonist
Platelet activating factor
agonist
CD16 antigen
antagonist
Anti-RhD
immunoglobulin
antagonist
Thrombopoietin
receptor agonist
X
ITP
Oral
X
ITP
Oral
X
ITP
Oral
X
ITP
IV
X
ITP
IV
X
ITP
IV
X
ITP
IV
X
ITP
IV
X
Thrombocytopenia
Oral
Source: ADIS R&D Insight; IDDB3
16
Preclinical Pipeline
•
Several companies have active research programs targeting thrombocytopenia, but very little data are available to
assess activity.
Drug
Developer
MOA
Phase
Indication
ROA
XXXXX
XXXXX
IL-1 agonists
X
Thrombocytopenia
Injectable
XXXXX
XXXXX
X
TTP
Injectable
XXXXX
XXXXX
X
XXXXX
X
Chemo-induced
thrombocytopenia
Thrombocytopenia
Injectable
XXXXX
XXXXX
XXXXX
X
Thrombocytopenia
Injectable
XXXXX
XXXXX
X
ITP
IV
XXXXX
XXXXX
X
ITP
Injectable
XXXXX
XXXXX
ADAM protein
stimulants
Thrombopoietin
receptor agonist
VPAC1 receptor
antagonist
LG543 growth factor
agonist
Anti-RhD
immunoglobulin
antagonist
Staphylococcal protein
A down regulates
human B-lymphocyte
and macrophage
activation
Platelet activating factor
agonist
X
Thrombocytopenia
IV
IV
Source: ADIS R&D Insight; IDDB3
17
Key Trials Overview
•
•
•
Most pipeline competitors have focused on ITP as their lead indication for registration.
– GSK fielded two phase III studies (up to 200 subjects) and Amgen’s phase III had 210 subjects.
– Most trials involve patients who are relapsed after at least one standard therapy or are refractory.
Thrombocytopenia related to hepatitis C or chronic liver disease is another area of investment, where trial sizes are
much larger (up to 750 patients).
– HCV related studies aim to address thrombocytopenia such that patients can initiate and/or stay on antiviral
therapy.
Other thrombocytopenia studies in late phases address MDS and chemotherapy patients.
18
Key Trials: Promacta (Eltrombopag) in ITP
Compound
Cancer
Sponsor
Phase
Patients
Promacta
ITP
GSK
III
200
Promacta
ITP
GSK
III
189
Promacta
ITP
GSK
II
99
Design
Primary
Endpoints
EXTEND: Open-label, dose-adjustment,
Safety and
extension to evaluate safety and efficacy of tolerability, clinical
eltrombopag for treatment of subjects with ITP lab tests, ocular
previously enrolled in an eltrombopag trial.
exams and
Study allows individualized dose and schedule frequency of all
for each subject. Ability to reduce the dose of AEs
concomitant ITP medications in the presence of
eltrombopag, while maintaining platelet counts
= 50,000/microL will be investigated.
RAISE: Randomized, double-blind, placebo- Pts w/ platelet
counts between
controlled study, to evaluate efficacy, safety
50,000/uL and
and tolerability of eltrombopag, initially
administered as 50 mg oral tablets once daily 400,000/uL during
for six months in adult subjects with previously the 6 month
treated chronic ITP. Subjects randomized 2:1, treatment period
eltrombopag to placebo, and will be stratified
based upon splenectomy status, use of ITP
medication at baseline and baseline platelet
count less than or equal to 15,000/µL.
Randomized, double blind trial to assess
Pts achieving
efficacy, safety, tolerability in adults with
platelet counts
refractory, chronic ITP. Entry platelet counts =50,000/microL
<30,000/microL for 6 mos who have failed at after 42 days of
least one treatment; also included pts receiving treatment
chronic maintenance steroids.
Secondary
Timing
Endpoints
Proportion of
Start Jun 2006;
patients achieving end Jul 2010
target platelet
counts and
duration of count
elevation; signs
and symptoms of
ITP; QOL
Duration of count Start Nov 2006;
elevation;
end Jul 2008
frequency of AEs;
need for rescue
treatment or ITP
med; ITP
symptoms; safety
& tolerability
Safety &
tolerability; PK;
PD; ITP
symptoms, QOL
Start Apr 2005;
complete
Source: ClinicalTrials.gov
19
Key Trials: Promacta (Eltrombopag) in HCV-related Thrombocytopenia
Compound
Cancer
Sponsor
Phase
Patients
Promacta
HCV
GSK
III
750
Promacta
HCV
GSK
III
500
Design
Primary
Secondary
Timing
Endpoints
Endpoints
Randomized, placebo controlled study in pts w/ SVR rate defined Pts with a shift in Start Oct 2007;
chronic HCV to assess ability of eltrombopag to as percentage of platelet count from end Aug 2011
maintain a platelet count sufficient to facilitate subjects with non- <75,000/µL to
initiation of antiviral therapy (Peg IFN alfadetectable HCV- >/=90,000/µL;
2a+ribavirin), to minimize antiviral therapy dose RNA at 24 weeks AEs, laboratory
reductions and to avoid permanent
post-completion of abnormalities,
discontinuation of antiviral therapy. The clinical the planned
ocular
benefit of eltrombopag will be measured by the treatment period examinations, 12proportion of subjects who are able to achieve (i.e., Week 48 for lead ECGs
a Sustained Virological Response (SVR).
genotype 2/3 or
Entry platelet count of <75,000/microL.
Week 72 for nongenotype 2/3)
Randomized, double blind trial to assess
Need for platelet Bleeding; AEs, lab Start May 2008
platelet elevation to reduce need for platelet
transfusion prior abnormalities,
transfusions in chronic liver disease patients to, during and up ocular exams,
with thrombocytopenia undergoing elective
to seven days
ECGmb
invasive procedures; includes patients with
following elective
HCV, HBV, HIV, non-alcoholic steatohepatitis, invasive
NASH. Patients with model of end stage liver procedures
disease score (MELD) of 24 or less; entry
platelet count <50,000/microL
Source: ClinicalTrials.gov
20
Key Trials: Promacta (Eltrombopag) in HCV and Chemo-related Thrombocytopenia
Compound
Cancer
Sponsor
Phase
Patients
Promacta
HCV
GSK
II
422
Promacta
CIT
GSK
II
183
Design
Primary
Endpoints
Randomized, double blind dose ranging study Pts shifting from
(30, 50, 75 QD for 12 weeks) in chronic HCV baseline counts to
related thrombocytopenia who are potential
100,000/microL
candidates for antiviral therapy.
after 4 weeks
Secondary
Endpoints
Mean increase in
platelet counts;
safety &
tolerability;
population PK;
PD; effect of
antiviral outcome
measures
Randomized, double blind dose ranging study Change in
Safety &
to assess efficacy, safety, PK in patients
baseline platelet tolerability; PD;
receiving multiple cycles of chemo. Included count from 1st day platelet count
pts with advanced solid tumors scheduled to of 2nd cycle to
change; dose
receive 1st line carboplatin/paclitaxel; subjects lowest count
intensity of
had no history of platelet or bleeding disorders. observed in the carbo/paclitaxel
cycle
Timing
Start Feb 2005;
complete
Start Apr 2005;
end Feb 2007
Source: ClinicalTrials.gov
21
Key Trials: Nplate (Romiplostim) in ITP
Compound
Cancer
Sponsor
Phase
Patients
Nplate
ITP
Nplate
ITP
Design
Amgen
II
100
Open label study in refractory ITP patients.
Entry platelet count <=20,000/microL; failed at
least 3 conventional treatments; on anticoagulant medication if pt has AF history.
Amgen
III
210
3b, randomized, SOC-controlled, open-label,
52-week treatment study to compare AMG 531
to medical SOC for ITP, with a 6-month Safety
Follow-up. Non-splenectomized subjects who
are 18 years or older, are diagnosed with ITP
according to the American Society of
Hematology (ASH) guidelines, and who have
received at least 1 prior therapy for ITP will be
eligible to screen for this study. Eligible
subjects will be randomized to AMG 531 or
medical SOC for ITP if their platelet count is <
50,000 or their platelet count falls to < 50,000
during or after a clinically-indicated taper or
discontinuation of current ITP therapy. After the
completion or discontinuation of the study
treatment period, any subject who does not
transfer in to another AMG 531 study will
complete a 6-month Safety Follow-up period.
Primary
Secondary
Endpoints
Endpoints
AEs; clinically
Platelet response;
significant
transfusions
changes in lab
values and
incidence of
antibody formation
Number of pts
Time to
undergoing
splenectomy;
splenectomy;
platelet response;
number of
change in ITP
treatment failures patient reported
outcomes
Timing
Start Feb 2005;
end Dec 2010
Start Nov 2006;
end Jan 2010
Source: ClinicalTrials.gov
22
Key Trials: Nplate (Romiplostim) in MDS
Compound
Cancer
Sponsor
Phase
Patients
Nplate
MDS
Amgen
II
240
Nplate
MDS
Amgen
N/A
200
Design
Primary
Endpoints
Randomized, double blind, placebo controlled Efficacy
study evaluating efficacy and safety of
treatment of thrombocytopenia in pts w/ low or
intermediate-1 risk MDS. Starting dose of
750mcg up to 1000mcg or reduced to min of
250 mcg.
Open label extension study to evaluate safety AEs
of long term dosing in MDS. Patients with
IPSS low or intermediate-1 risk MDS.
Secondary
Timing
Endpoints
Number of platelet Start May 2008;
transfusions,
end Jan 2011
bleeding events;
platelet
hematological
improvement;
overall survival;
disease
progression to
AML; neutralizing
antibodies versus
drug; all AEs
Platelet response; Start Jun 2007;
transfusions;
end Sep 2010
bleeding events
Source: ClinicalTrials.gov
23
Key Trials: Nplate (Romiplostim) in MDSKey Trials: Other Phase II Compounds
Compound
Cancer
Sponsor
Phase
Patients
XXXXX
ITP
XXXXX
II
106
XXXXX
ITP
XXXXX
II
65
XXXXX
ITP
XXXXX
II
24
XXXXX
ITP
XXXXX
II
66
Design
Primary
Endpoints
Open label, single arm study will evaluate the Overall response
efficacy and safety of rituximab monotherapy in rate
patients with refractory, relapsing or chronic
idiopathic thrombocytopenic purpura (ITP).
Patients will receive infusions of 1000mg i.v. on
days 1 and 15. The anticipated time on study
treatment is 3-12 months.
Secondary
Timing
Endpoints
Time to CR and Start May 2007;
PR; duration of end Nov 2009
response and time
to new therapy;
AEs;
hematological
toxicity; infections;
infusion reactions
Double-blind, randomized, placebo-controlled, Platelet response PK; PK/PD
dose-ranging, parallel-group study will assess
relationship
the efficacy, safety and tolerability. Once daily
oral doses of 2.5, 5, 10, 20 mg or placebo for
28 days. Patients are refractory or relapsed
after at least one prior therapy; entry platelet
counts <50,000/mm3.
Randomized, double blind placebo controlled Platelet counts
Start Mar 2008;
end May 2009
study in ITP with open label extension.
Patients dosed 7.5 mg/day for 6 weeks.
Includes patients with platelet counts
<50,000/microL who have been treated with at
least 1 ITP therapy.
Phase I/II, non-randomized, open label dose
Start Nov 2007
comparison study. Includes adults with chronic
IPT that have failed at least one therapy. Entry
platelet counts <30,000/microL and platelet
levels <150,000/microL for >6 mos. Drug
dosed twice, two weeks apart.
Source: ClinicalTrials.gov
24
Conclusions
Populations are small to moderate
•
•
•
•
More than 200,000 patients in the US experience thrombocytopenia.
Drug-induced thrombocytopenia (heparin, chemo or other drugs) are most common.
Thrombocytopenia resulting from compromised liver function (chronic HCV infection and cirrhosis) is also a
significant contributor to incidence.
Estimates of ITP incidence span a large range (XXXX-XXXX/year), but condition is still considered rare.
–
–
Small population allows for orphan designation and fast track or priority review
Unmet need qualifies for fast tract or priority review
Competition is poised to intensify
• Treatment aims to address the underlying cause of thrombocytopenia (e.g., withdrawal of myelosuppressive therapy;
antiviral therapy, liver transplant etc.).
• In ITP, most treatments are immunomodulators targeting production or interaction of autoantibodies targeting
platelets (e.g., IVIG, anti-D, rituximab).
• New TPO mimetics are poised to enter the market in 20XX.
– Amgen and GSK will specifically address thrombopoiesis with new oral and injectable therapies which have reported high
(>75%) response rates in restoring platelets to safe levels.
– Both will significantly change competitive landscape with investments in advertising, promotion and sales to create share of
voice.
25
Conclusions
Clinical pipeline is limited
•
•
Only 11 compounds have entered the clinic and 8 appear to be in preclinical development.
Several are focused on the TPO receptor, while others are immunomodulators or other MOAs.
–
TPO agents hold the most promise at this time, with Amgen and GSK in the lead.
Clinical trials focus on ITP, but also HCV
• Most competitors have focused on ITP as their lead indication for registration, due to potential for fast track or
priority review.
– Phase II and III studies require 100-200 patients
• Companies have also fielded several studies in patients with chronic HCV infection and liver disease and Amgen
has a large trial in MDS.
– Phase III studies with HCV patients are larger (~500-750 patients)
• Amgen, GSK and others are looking at chemotherapy induced thrombocytopenia, but investigation appears to be in
phase II to date.
• Based on additional safety studies being fielded, long-term use and safety are significant concerns. Specific studies
are evaluating ocular effects.
26
Emerging Profile
New agents must be effective, with relatively low toxicity
Emerging Profile based on Clinical Pipeline
MOA
• Target TPO receptor or autoantibody activity
Indication(s)
• ITP (lead)
• Thrombocytopenia related to chronic HCV or liver disease
• Chemotherapy-induced thrombocytopenia (CIT)
ROA and Dosing
• Oral or subcutaneous dosing
• QD
Efficacy
• 75-90% response, measured by achievement of platelet counts
≥50,000/µL
• Duration of response ≥15 weeks
• Reduced need for platelet infusions
Safety
•
•
•
•
Well tolerated; similar to placebo
Mild headaches and fatigue
Rare grade 3 or 4 toxicities (e.g., bleeding / thrombosis)
Ocular effects TBD
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Key References
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•
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•
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•
Armstrong GL, et al, “Prevalence of Hepatitis C Virus Infection in the United States, 1999-2002,” Ann Intern Med, 2006
Beardsley DS, “ITP in the 21st Century,” Hematology, 2006
CDC, HIV/AIDS Surveillance Report, 2005
Chong-Shan W, et al, “Strong Association of Hepatitis C Virus Infection and Thrombocytopenia,” Clinical Infectious
Diseases, 2004
Cines DB, et al, “Congenital and Acquired Thrombocytopenia, Hematology, 2004
Frederiksen H, Schmidt K, “Incidence of Idiopathic Thrombocytopenic Purpura in Adults Increases with Age,” Blood,
1999
Decision Resources, “Managing the Side Effects of Chemotherapy,” 2007
George JN, et al, “ITP: A Practice Guideline Developed by Explicit Methods for the American Society of Hematology,”
Blood, 1996
Hagop K, et al, “Incidence and Impact of Thrombocytopenia in Myelodysplastic Syndromes,” Cancer, 2007
Ma X, et al, “Myelodysplastic Syndromes: Incidence and Survival in the US,” Cancer, 2007
Moore R, www.hopkins-hivguide.org
Ohman EM, et al, “Identification, Diagnosis and Treatment of HIT and Thrombosis (CATCH Registry),” J Thromb
Thrombolysis, 2005
Panzer S, “New Therapeutic Options for Adult Chronic ITP, Vox Sanguinis, 2008
28
Dan Meichenbaum
415.828.5265
dmeichenbaum@dectiva.com
Will Anlyan
347.334.2562
wanlyan@dectiva.com
www.dectiva.com
Follow us on Twitter! @Dectiva
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