2016 completed clinical trials industry strategies revealed and graded

1. 2016 Completed
Clinical Trials: Industry
Strategies Revealed
and Graded

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Company pipeline depictions are snapshots that
illustrate, at that point in time, where a therapeutic
candidate sits in terms of development stage for
a specific therapy area or disease. These static
views lack the granular detail that informs just how
well biopharma have performed year over year,
other than noting candidate advances or dropouts.
Assessing clinical trial completions provides
those details needed to support comparisons of
companies’ strategies and performances. This
analysis examines the landscape of industry-
sponsored clinical trials completed in 2016.1
Trials
terminated in this same period are analyzed
separately.
Similar analyses on trial completions were reported
for 2014 and 2015.2
Snapshot data taken for 2015
and 2016 were nearly identical with respect to the
date when data was exported: February 11, 2016
(3028 completed trials) and February 13, 2017
(3420 completed trials), respectively.3
Oncology trial
completions dominated the landscape with 826
trials, but at the disease level, Type 2 diabetes took
top spot with 190 completed trials. For terminated
trials, in 2015 there were 459 trials and in 2016, 603
trials were terminated. Oncology topped 2016 trial
terminations, and 53 of these trials focused on non-
small cell lung cancer (NSCLC).
Introduction
Christine Blazynski, Ph.D.
Innovation Head
Informa Pharma Intelligence
1 Snapshot data was taken from Informa Pharma Intelligence’s Trialtrove on Feb 13, 2017. The search was limited to
industry-sponsored trials with end dates between Jan 1, 2016 and Dec 31, 2016. Trialtrove defines the end date as the
date a trial completes or is expected to complete, or the report of primary endpoints.
2 The analysis of trials completed in 2014 can be requested at pharma@informa.com while the analysis for 2015 is
available at https://pharmaintelligence.informa.com/resources/product-content/clinical-trial-landscape.
3 During 2016, Trialtrove added seven disease conditions to its portfolio, thereby accounting for a significant part of
the nearly 400 trial increase.

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Therapeutic Areaa
Ranking Trial count
2016 2015 2016 2015
Oncology 1 1 826 756
Autoimmune/Inflammation 2 3 677 486
CNS 3 2 547 513
Metabolic/Endocrinology 4 4 516 435
Infectious Diseasesb
5 5 435 374
Cardiovascular 6 6 249 227
Vaccines 7 7 149 67
Ophthalmology 8 8 80 73
Genitourinary 9 9 72 64
Top-line Trial Landscape Metrics
Oncology trial completions comprised the largest
numbers of trials in both 2016 and 2015 (Table
1). Trials looking at diseases in the Autoimmune/
Inflammatory (AI) space were the second most
frequent, followed by Central Nervous System
(CNS). The rank order of these two therapy areas is
reversed, compared to the 2015 report. The other
therapeutic areas remained unchanged from the
2015 report. This analysis will more deeply assess
the sponsors, drug development strategies, top
diseases trial success, and more for these top three
therapeutic areas.
Across all therapy areas, more Phase I trials, as
expected, completed last year compared to later
phase trials (Figure 1). For Phase III trials, Vaccines,
Cardiovascular, and CNS accounted for more than
30% of all completed trials; Oncology and Infectious
Diseases (not including vaccines) saw the smallest
proportions of trials (3% and 14%, respectively).
Among Phase II trial completions, Oncology trials
accounted for one-third of the total trials, followed
by Ophthalmology (31.3%), AI (27.3%) and CNS
(26%).
Trialtrove analysts assess reported results for trials
when available, and for this snapshot data set,
just under 30% of the trials attained their primary
outcome. Slightly more than 60% of the trials either
had no results reported in the public domain, or their
final outcome was unknown. This high percentage
is not surprising since it often is the case that full
reporting of trial results can take many months if
not years.
Table 1. 2015/2016 Therapeutic area ranking for completed, industry-sponsored trials
a
Trials may span multiple therapeutic areas
b
Not including vaccines
Source: Trialtrove, February 2017

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Figure 1. Distribution of industry-sponsored trials completed in 2016 by therapy areaa
and phase
a
Individual trials may involve diseases in more than one therapy area.
b
Not including vaccines
Source: Trialtrove, February 2017
Diseases with more than 120 completed trials
spanned four therapy areas. A comparison of the top
five ranked diseases over the past three years shows
Type 2 diabetes consistently in first place (Table
2). Respiratory infection trials have risen in rank in
each of the past three years. The overall count of
trials completed in 2014 is higher; this is likely due
to taking the data snapshot two weeks later which
allows for discovery of intelligence around trial
completions.
Table 2. Top ranked diseases* for trials completed in the past three years#
* Unspecified solid tumors (131 trials with 110 Phase I trials) not included in rankings
#
2014 Snapshot data taken on March 3, 2015
Source: Trialtrove®
, February 2017
Disease 2016 2015 (rank) 2014 (rank)
Type 2 diabetes 190 180 (1) 315 (1)
Respiratory Infections 184 122 (3) 196 (4)
HCV 162 127 (2) 215 (2)
Non-small cell lung cancer 122 110 (4) 200 (3)
Rheumatoid Arthritis 114 95 (5) 173 (5)
I I/II II II/III III III/IV
Genitourinary
Ophthalmology
Vaccines
Cardiovascular
Infectious Diseasesb
Metabolic/Endocrinology
CNS
Autoimmune
Oncology
0 200 400 600 800100 300 500 700 900
# of Trials
Therapyarea

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However, when you look across the top diseases for
trials attaining their primary endpoint, the disease
rankings differ (Table 3). Relative to the total number
of trials completed in each disease, nearly 50%
of colorectal cancer trials hit their endpoints. The
top four diseases, on a relative basis, were all in
oncology. But, of note is the fact that 30 of 52 Type
2 diabetes’ Phase III trials hit primary endpoint.
Table 3. Trials attaining primary endpoint(s) by disease* and phase
* Unspecified solid tumors (40 trials with 34 Phase I trials) not included in rankings
Source: Trialtrove®
, February 2017
Disease I I/II II II/III III III/IV
Total
(rank)
% of all
trials
Colorectal cancer 21 5 11 - 4 - 41 (4) 47.7%
Breast cancer 18 7 13 - 13 - 51 (2) 42.9%
Non-small cell lung cancer 22 9 13 - 5 - 49 (3) 40.2%
Nociceptive pain 1 3 9 2 18 - 33 (7) 35.9%
Non-Hodgkin’s lymphoma 12 6 10 - 4 - 32 (8) 34.8%
Chronic obstructive pulmonary
disease
3 - 8 - 14 1 26 (9) 28.3%
Type 2 diabetes 6 - 16 - 30 - 52 (1) 27.4%
Psoriasis 3 2 2 - 15 - 22 (12) 26.8%
Hepatitis C 1 1 12 2 25 - 41 (4) 25.3%
Asthma 1 - 8 1 14 - 24 (10) 24.0%
HIV - 3 1 7 1 8 20 (13) 22.2%
Rheumatoid arthritis - 2 8 1 12 - 23 (11) 20.2%
Respiratory infections 6 4 7 2 17 - 36 (6) 19.6%

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Completed Trials’ Landscape: Sponsor Assessment
The top sponsor with completed trials in 2016 is
Novartis, with a total of 165 trials (Table 4); the
company has maintained this ranking for three
consecutive years. Roche moved back into second
place, while both GlaxoSmithKline (GSK) and Pfizer
rose by one ranking. Merck, on the other hand,
dropped from second place in 2015 to fifth in 2016.
Table 4. Top five sponsors* with completed trials
* Includes co-sponsored trials
Source: Trialtrove®
, February 2017
Sponsor 2016 2015 (rank) 2014 (rank)
Novartis 165 147 (1) 265 (1)
Roche 160 123 (3) 244 (2)
GlaxoSmithKline 158 119 (4) 239 (3)
Pfizer 140 120 (5) 225 (4)
Merck 134 127 (2) 203 (5)

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Sponsor Trials Attaining Primary Endpoint(s)
Total Completed
Trials#
(Rank)
% Success
I I/II II II/III III III/IV Sum
Novo Nordisk 1 - 2 - 15 - 18 39 (17) 46%
Otsuka 5 1 5 - 9 - 20 47 (16) 43%
Amgen 3 3 6 - 17 - 29 71 (14) 41%
Novartis 5 8 24 - 21 - 58 165 (1) 35%
AbbVie 2 1 7 1 17 - 28 82 (12) 34%
Bayer 4 2 10 1 8 - 25 73 (13) 34%
Teva 1 - 5 - 4 - 10 30 (18) 33%
Johnson & Johnson 8 2 12 - 17 - 39 127 (7) 31%
Roche 8 4 17 - 17 - 46 160 (2) 29%
Takeda*
7 4 4 1 9 - 25 87 (10) 29%
Gilead 3 - 10 1 10 - 24 86 (11) 28%
GlaxoSmithKline 5 3 13 - 20 - 41 158 (3) 26%
Merck 7 - 6 2 20 - 35 134 (6) 26%
Pfizer 8 1 8 - 18 - 35 140 (5) 25%
Sanofi 2 1 4 1 16 - 24 97 (8) 25%
Boehringer Ingelheim 3 - 8 - 5 1 17 67 (15) 25%
AstraZeneca 3 2 13 - 17 - 35 153 (4) 23%
Eli Lilly 5 1 7 - 7 - 20 88 (9) 23%
When assessing the sponsors’ successful trials
across the top three therapeutic areas, Novartis
remains at the top with a total of 58 trials,
followed by Roche, GSK and Johnson and Johnson
(J&J) (Table 5). Pfizer and Merck tie for fifth rank.
Nevertheless, relative to a sponsor’s total completed
trial count, Novo Nordisk is the clear winner,
followed by Otsuka, Amgen and Novartis. Bayer and
AbbVie share fifth spot with 34% success, with Teva
a close sixth place.
Table 5. Top sponsors* with trials attaining primary outcomes
* Includes Ariad whose acquisition by Takeda closed February 16, 2017
#
Count includes trials with other co-sponsors
Source: Trialtrove, February 2017

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Across all oncology completed trials, 38.9% met
primary outcomes. The sponsors with the five
highest numbers of completed trials include Roche,
Novartis, Pfizer, Amgen and Eli Lilly (Lilly) (Table
6). However, when assessing the top completers
by success rate, those sponsors holding the top
five spots are very different: J&J, Otsuka, Amgen,
Boehringer Ingelheim (BI) and Celgene.
Deep Dive into the Top Three Therapy Areas: Oncology,
Autoimmune/Inflammation and CNS Landscapes
Therapeutic Areas
Table 6. Top sponsors for completed Oncology trials and success rate4
Source: Trialtrove, February 2017
4 Indeterminate designation is assigned to trials when the outcome is neither clearly positive or negative. Unknown is given to trials that have not yet
reported full results for the primary endpoint(s). N/A is applied to trials that do not include efficacy and/or safety outcomes.
Sponsor
Negative
outcome/
primary
endpoint(s)
not met
Outcome inde-
terminate
Outcome
unknown
Positive
outcome/
primary
endpoint(s)
met
N/A
Total
Trials
(Rank)
Success
Rate*
Johnson & Johnson - 2 1 13 4 20 (12) 65.0%
Otsuka 1 1 3 11 2 18 (14) 61.1%
Amgen 5 3 12 18 2 40 (4) 45.0%
Boehringer Ingelheim 3 2 4 8 2 19 (13) 42.1%
Celgene 2 5 8 13 3 31 (9) 41.9%
Bayer 1 3 4 11 9 28 (10) 39.3%
Novartis 6 3 31 29 7 76 (2) 38.2%
Takeda 4 6 5 13 7 35 (8) 37.1%
Pfizer 4 4 8 14 12 42 (3) 33.3%
AbbVie 2 2 6 5 - 15 (15) 33.3%
Roche 14 12 24 28 13 91 (1) 30.8%
GlaxoSmithKline 2 1 14 8 2 27 (11) 29.6%
AstraZeneca 7 4 10 9 6 36 (6) 25.0%
Eli Lilly 5 4 11 9 9 38 (5) 23.7%
Sanofi 6 5 15 8 2 36 (6) 22.2%

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Table 7. Top sponsors for completed Autoimmune/Inflammation trials and success rate4
For completed AI trials, the overall success rate was
lower than for oncology: 29.2%. GSK leads the pack
with 49 trials (Table 7), followed by AstraZeneca
(AZ; 45) Roche (36), Pfizer and Chiesi (28 each) and
Novartis (27). Nevertheless, when ranked by trial
success rates, the sponsors with the highest success
are AbbVie, J&J, the co-sponsor team of Regeneron/
Sanofi, Teva and Vertex tied for 4th rank, followed by
Lilly.
* Includes trials co-sponsored with Regeneron
Source: Trialtrove, February 2017
Sponsor
Negative
outcome/
primary
endpoint(s)
not met
Outcome
indeterminate
Outcome
unknown
Positive
outcome/
primary
endpoint(s)
met
N/A
Total
Trials
(Rank)
Success
Rate
AbbVie - - 6 10 1 17 (9) 58.8%
Johnson & Johnson 1 5 3 9 3 21 (8) 42.9%
Regeneron Sanofi 1 1 3 5 3 13 (11) 38.5%
Teva - 1 1 4 5 11 (13) 36.4%
Vertex - 3 2 4 2 11 (13) 36.4%
Eli Lilly - 2 2 4 4 12 (12) 33.3%
Pfizer 1 2 7 9 9 28 (4) 32.1%
Chiesi 1 2 7 9 9 28 (4) 32.1%
Sanofi* 2 1 3 5 5 16 (10) 31.3%
Novartis 4 3 11 8 1 27 (6) 29.6%
AstraZeneca - 5 14 13 13 45 (2) 28.9%
Bristol-Myers Squibb - 1 - 3 7 11 (13) 27.3%
GlaxoSmithKline 1 6 14 13 15 49 (1) 26.5%
Boehringer Ingelheim 1 - 1 5 16 23 (7) 21.7%
Gilead - 2 - 2 6 10 (18) 20.0%
Celgene 1 - 1 2 7 11 (13) 18.2%
Roche 2 10 12 5 7 36 (3) 13.9%
Leo Pharma - 2 6 1 2 11 (13) 9.1%

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Sponsor
Negative
outcome/
primary
endpoint(s)
not met
Outcome
indeterminate
Outcome
unknown
Positive
outcome/
primary
endpoint(s)
met
N/A
Total
(Rank)
Success
Rate
Teva - - 1 5 1 7 (22) 71.4%
Lundbeck Otsuka - - 3 5 1 9 (13) 55.6%
Novartis 1 - 2 6 2 11 (8) 54.5%
Roche 1 - 1 3 3 8 (16) 37.5%
Sumitomo Dainippon
Pharma
1 1 2 3 1 8 (16) 37.5%
Otsuka*
2 2 7 6 1 18 (3) 33.3%
Allergan 2 3 6 5 - 16 (6) 31.3%
Lundbeck**
- - 9 5 3 18 (3) 27.8%
Sanofi 2 - 3 3 3 11 (8) 27.3%
Alkermes 2 - 1 2 3 8 (16) 25.0%
Johnson & Johnson - - 2 4 13 19 (2) 21.1%
AbbVie 1 - 5 2 2 10 (12) 20.0%
Eli Lilly 1 - 1 2 7 11 (8) 18.2%
Boehringer Ingelheim - - 1 1 6 8 (16) 12.5%
Biogen 1 - 6 2 9 18 (3) 11.1%
Pfizer 2 2 8 3 13 28 (1) 10.7%
Daiichi Sankyo - - 4 1 6 11 (8) 9.1%
Takeda - 2 6 - 6 14 (7) 0.0%
Merck 1 - 4 - 4 9 (13) 0.0%
GlaxoSmithKline - 2 3 - 4 9 (13) 0.0%
Acorda Therapeutics 1 - 1 - 6 8 (16) 0.0%
UCB - 3 2 - 3 8 (16) 0.0%
Astellas - 2 3 - 1 6 (23) 0.0%
Table 8. Top sponsors for completed CNS trials and success rate4
The overall success rate for completed trials in CNS
trailed at 23.4%. Sponsors with the five highest
numbers of trials are: Pfizer, J&J, a three-way tie
for third among Biogen, Lundbeck and Otsuka,
and Allergan and Takeda at fourth and fifth place,
respectively (Table 8). Of note, nine of the 18 trials
for Lundbeck and Otsuka were co-sponsored. In
addition, these partners did quite well in terms of
success rate, coming in at 55.6% behind the clear
leader, Teva, with 71.4% trials hitting endpoints.
* Includes count of trials co-sponsored with Otsuka
** Includes count of co-sponsored trials
Source: Trialtrove, February 2017

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Granular clinical trial data, when analyzed, can
reveal details of a company’s drug program strategy.
To derive the most value from the trial data, the
study drugs for Phase II, II/III and III Oncology, CNS
and AI trials were researched and labeled as either
novel, label expansion, me-too, biosimilar, generic
or OTC. Additional labels for new delivery, new
formulation or new combination were also applied.
Study drugs very rarely received more than one
label; for example, a me-too drug may have been
involved in a new combination or new formulation.
Label Criteria:
• The novel label was applied based on the drug
development and regulatory status in the trial-
site countries at the time that the trial started.
• Me-too was applied based on the study drug
mechanism of action, and whether a similar drug
was launched in one of the countries involved in
the trial at the time of study initiation.
• Label-expansion was applied when the study
drug was approved in a market beyond those
countries in the trial and at the time when the trial
initiated, if the disease focus/use or line of therapy
was not included in the drug label, or if another
patient population was being studied (pediatric for
example).
• The biosimilar label was applied to biosimilar
candidates.
• Generic and OTC (OTC tags included nutraceuticals
or nutritional supplement) labels were applied for
any of these types of study drugs, respectively.
• For marketed drugs that were combined with
either a novel or other approved drug, and the
combination was not yet approved by a regulatory
body in one of the countries involved in the trial,
at the time of initiation, the new combination was
applied.
• The same criteria as above was used to tag
study drugs that involved new delivery or new
formulation strategies.
The drug strategies in each of the top therapy areas
showed some marked differences (Figure 2). Trials
involving novel drugs were more frequent in AI trials,
while trials with label-expansion strategy dominated
the oncology landscape. For CNS completed trials,
me-too’s were the most prevalent. The phase
distribution of strategy tags is useful in informing
competitors, payors or providers about what is on
the near-term and longer-term horizon (Figure 3 A,
B, C). For example, where the relative distribution
of strategy labels change from Phase III to Phase
II, that may well indicate the potential for market
share erosion (more me-too’s in Phase II compared
to Phase III) from the drug developer perspective.
And from the perspective of the payor, this might be
indicative as having potential to lower costs.
For Oncology, the relative shape of the histograms
(Fig. 3A) in Phase II and III is similar, with trials for
label-expansion significantly outnumbering those
with novel therapies. Expanding therapeutic uses is
the norm in this space: advancing lines of therapy
as well as moving from tumor type to tumor type.
Among the AI trials, there are very few biosimilar
drugs in Phase II, but the relative ranking of novel
drugs is much higher in Phase II compared to
Phase III (Fig. 3B). Certainly, there will be Phase II
candidates that drop out of development, but this
picture does suggest the possibility of new drugs
that may challenge the current leading therapies.
Industry Sponsor Drug and Disease Strategy
Oncology, Autoimmune/Inflammation, CNS Strategies

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And yet another story can be woven from the
CNS drug strategy by trial phase (Fig. 3C). Trials
designed to test me-too drugs look to continue over
the next several years. There were three trials in
Phase II and III for new drug-combinations. These
may potentially improve patient compliance, thus
increasing efficacy – a scenario that bodes well for
pharma, payers and patients. Of note is the shift
seen between Phase II and III in relative position
between novel therapy trials and label-expansion
(as seen for AI). Phase II trials that involved me-
too drugs number nearly the same as for Phase III
completed trials and may foreshadow continued
brand erosion in this disease domain.
The decline in Phase II CNS trials that appear to be
aimed at expanding into a new disease, market or
patient sub-population, along with the dearth of
trials hitting endpoints, has been the norm for CNS
over the last five years or longer. In the past decade,
the pace of first-in-class drug approvals has declined
(especially for affective disorders and neurologic
disorders, and particularly Alzheimer’s disease).
Figure 2. Sponsor drug development strategies
Source: Trialtrove, February 2017
250
200
150
100
50
0
TrialCount
Oncology
novel
label-expansion
me-too
biosimilar
OTC
newdelivery
newcombination
novel
label-expansion
me-too
biosimilar
generic
OTC
newcombination
newdelivery
newformulation
novel
label-expansion
me-too
generic
OTC
newformulation
newcombination
newdelivery
Autoimmune/Inflammation CNS

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Figure 3A. Oncology drug strategy by trial phase
Figure 3C. CNS drug strategy by trial phase
Source: Trialtrove, February 2017
160
140
120
100
80
60
40
20
0
70
60
50
40
30
20
10
0
TrialCountTrialCount
Phase II
Phase II
Phase III
Phase III
Phase II/III
Phase II/III
Phase III/IV
novel label-expansion me-too biosimilar OTC new delivery
novel label-expansion me-too generic, label expansion OTC
new combination
Figure 3B. Autoimmune/Inflammation drug strategy by trial phase
120
100
80
60
40
20
0
TrialCount
Phase II Phase IIIPhase II/III Phase III/IV
novel label-expansion me-too biosimilar OTC new delivery
new combination new delivery new formulation
new formulationnew combination new delivery

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Clinical trials that completed, involved novel drugs,
and hit their primary endpoints are the clear
winners; there were a total 86 Phase II, 3 Phase
II/III and 60 Phase III trials in this set. The list of
industry sponsors who had two or more successful
trials involving novel drugs is relatively small (Table
9). Novartis topped the leaderboard with twelve
trials, three of which were co-sponsored with
Amgen. The two companies have combined efforts
on erenumab, a calcitonin receptor-like receptor
antagonist, in endometrial cancer, Hodgkin’s
lymphoma and migraine. Novartis also partnered
with GSK and Array Biopharma on separate trials for
melanoma and endometrial cancer, respectively.
Novartis’ solo trials included trials for asthma,
breast cancer, non-small cell lung cancer (NSCLC),
melanoma (2 trials), migraine (2 trials) and multiple
sclerosis (2 trials). Across the three therapeutic areas
data set of 1422 trials, 26 involved industry co-
sponsors.
Companies’ Strategies
Table 9. Sponsors with two or more trials involving novel drugs and attaining primary endpoint in Oncology,
Autoimmune/Inflammation and CNS trials
Source: Trialtrove, February 2017
Sponsor II II/III III Total
Novartis1
6 - 6 12
Johnson Johnson 5 - 4 9
AstraZeneca 2 - 6 8
Regeneron / Sanofi - 1 4 5
GlaxoSmithKline 3 - 4 7
Eli Lilly 2 - 2 4
Pfizer 3 - - 3
Amgen / Novartis 1 - 2 3
Chiesi - - 2 2
AstraZeneca / Kyowa Hakko Kirin - - 2 2
Roche 1 - 2 3
Vertex 2 - 1 3
Minerva Neurosciences 2 - - 2
Ablynx 2 - - 2
Ono Pharmaceuticals 1 - 1 2
Steba Biotech - - 2 2
Boehringer Ingelheim 2 - - 2
Lundbeck / Otsuka - - 2 2
Stallergenes Greer 2 - - 2
Merck KGaA 2 - - 2
Merck / Sun Pharma - - 2 2
GW Pharmaceuticals - - 2 2
1
Includes co-sponsored trials

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Among the three therapy areas’ strategy-tagged
data, 53 trials clearly reported that they failed to
attain primary endpoints. Roche reported these
results for 6 trials, BI had 3, and Merck KGaA, Lilly,
OncoGenex/Teva, Bristol-Myers Squibb and AbbVie
had 2 each.
The number of trials completed where the study
drug(s) were approved by at least one regulatory
authority, and the trial focus appeared to be
expanded use or geographic reach, was 165 (Table
10). Roche led in this group of trials, with a total of
20 (2 trials co-sponsored), followed by Novartis with
Pfizer and Amgen sharing third ranking. Twenty-five
of the 165 trials involved industry co-sponsors.
Table 10. Sponsors with five or more trials involving label-expansion and attaining primary endpoint across
Oncology, Autoimmune/Inflammation and CNS
Sponsor*
II II/III III III/IV Total
Roche 13 - 7 - 20
Novartis 10 - 5 - 14
Pfizer 4 - 6 - 10
Amgen 5 - 5 - 10
AstraZeneca 4 - 5 - 9
Johnson Johnson 4 - 5 - 9
Bayer 5 - 2 - 7
AbbVie 3 1 3 - 7
Otsuka 1 - 6 - 7
Celgene 6 - 1 - 7
Merck 4 - 1 - 5
Boehringer Ingelheim 3 - 1 1 5
* Count includes co-sponsored trials
Source: Trialtrove, February 2017

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Among the trials involving novel drugs, the diseases
with the highest numbers of completed trials
were NSCLC (18), Non-Hodgkin’s Lymphoma (NHL;
15), breast cancer (13), prostate cancer (10) and
melanoma (8). The study drugs that were involved
in two or more trials are listed in Table 11, for each
of these diseases. Of the eight drugs that were
classified as novel at the time the trials initiated,
four have been approved by at least one regulatory
body. Informa Pharma Intelligence’s Biomedtracker
is bearish on Pfizer’s dacomitinib for NSCLC, bullish
on Pifzer and Amgen’s palbociclib for breast cancer
and slightly bullish on Takeda’s relugolix for prostate
cancer.
Company/Disease Strategies
Oncology
Table 11. Top study drugs for completed Oncology trials with novel drugs
#
Likelihood of approval (LOA) sourced from Informa Pharma Intelligence’s Biomedtracker
##
Source: Informa’s Biomedtracker
Source: Biomedtracker, Trialtrove, February 2017
Disease
Drug
(Trial count)
Lead
Company
LOA#
at
time of
trial start
LOA end of
2016
Trial Outcome(s)
Approval
date
NSCLC ceritinib (2) Novartis 37% Approved
Phase II trial outcome
indeterminate; Phase III trial
attained primary endpoint
April 2014
dacomitinib (2) Pfizer 35% 0%
Phase II trial attained
primary outcome; Phase II
trial outcome indeterminate
-
NHL obinutuzumab (3) Roche 35% 100%
Phase III trial outcome
unknown; negative outcome;
attained primary endpoint
Feb 2016
Breast palbociclib (2)
Pfizer (Amgen
partnered)
45%; 94% 100%
Phase III trial attained
primary endpoint; Phase III
trial outcome indeterminate
Feb 2015
depoxythilone (2)
Beijing Biostar
Technologies
- -
Phase III trial attained
primary endpoint
-
Prostate relugolix (2) Takeda 10% 35%
Phase II trial attained
primary outcome; Phase II
trial outcome unknown
-
padeliporfin (2) Steba Biotech 10% 10%
Two Phase II trials attained
primary outcome
estimate
April 2017##
Melanoma dabrafenib (2) Novartis 87% 100%
Two Phase II trial outcome
unknown; primary outcome
attained
May 2013

18. 18 / April 2017 © Informa UK Ltd 2017 (Unauthorized photocopying prohibited.)
Across this therapy area, five novel drugs were
involved in at least two asthma or psoriasis trials
(Table 12). For asthma, one of these drugs received
regulatory approval, and two candidates are no
longer in active development. Of the two remaining
therapies, Biomedtracker has significantly elevated
the Likelihood of approval (LOA) for fevipiprant,
Novartis’ chemoattractant receptor-homologous
molecule agonist (CRTH2). AZ’s interleukin-5
monoclonal antibody, benralizumab, has a higher
LOA score, likely due to the success of three Phase
III trials.
Autoimmune/Inflammation
Table 12. Top study drugs for completed Autoimmune/Inflammation trials with novel drugs
* Roche discontinued program in H2 2016
^ Novartis discontinued development for asthma in Q1 2016
Source: Biomedtracker, Trialtrove, February 2017
Disease
Drug
(Trial count)
Lead Company
LOA at
time of
trial start
LOA end
of 2016
Trial Outcome(s)
Approval
date
Asthma benralizumab (5) AstraZeneca 72% 77%
Five Phase III trials: primary
enpoint attained in three
trials; two trials outcome
unknown
-
lebrikizumab* (3) Roche 68% 0%
Three Phase III trials: one
attained primary endpoint;
one outcome unknown;
one failed to meet primary
endpoint
Asthma
discontinued
ligelizumab^ (2) Novartis 18% 0%
Both Phase II trials outcome
unknown
Asthma
discontinued
mepolizumab (2) GlaxoSmithKline 18%; 98% 100%
Phase III trial attained
primary endpoint; Phase III
trial outcome unknown
Dec 2016
fevipiprant (2) Novartis 18% 68%
Two Phase II trials: outcome
unknown; primary endpoint
attained
-
Psoriasis DFD-06 (3) Dr. Reddy's 20%; 59% 59%
Phase II, outcome unknown;
two Phase III outcome
unknown
ixekizumab (3) Eli Lilly 61% 100%
Three Phase III trials: one
attained primary endpoint;
one outcome unknown; one
indeterminate
-

19. April 2017 / 19© Informa UK Ltd 2017 (Unauthorized photocopying prohibited.)
Nociceptive pain and multiple sclerosis each had two
novel drugs involved in two trials, while Alzheimer’s
disease was represented by only one novel drug
with more than a single trial (Table 13). For the
latter, TauRx’s tau aggregation inhibitor is viewed
most positively by Biomedtracker’s analysts, moving
LOA from 17% to 44%; however, the LOA is below
average compared to other drugs historically for
same stage of development.
CNS
Table 13. Top study drugs for completed CNS trials with novel drugs
Source: Biomedtracker, Trialtrove, February 2017
Disease
Drug
(Trial count)
Lead
Company
LOA at
time of
trial start
LOA end of
2016
Trial Outcome(s)
Approval
date
Nociceptive
Pain (post-
surgical)
VVZ-149 (2) Vivozan 17% 17%
Two Phase II trials,
outcome unknown
-
Nociceptive
Pain
(osteoarthritis)
ABT-981 (2) AbbVie 16%; 24% 24%
Two Phase II trials,
outcome unknown
-
Multiple
Sclerosis
siponimod (2) Novartis 17%; 52% 56%
Phase II: primary endpoint
attained; Phase III:
primary endpoint attained
-
daclizumab high
yield process (2)
Biogen 57% 100%
Phase II: outcome
unknown; Phase III, NA
May 2016
Alzheimer's
leuco-
methythioninium
(2)
TauRx 17% 44%
Two Phase III trials:
outcome unknown;
primary enpoints not met
-

20. 20 / April 2017 © Informa UK Ltd 2017 (Unauthorized photocopying prohibited.)
Trials that involved biomarkers accounted for 45.3%
of Oncology completed trials (178 of 393 Phase II
– III/IV trials), 15% of AI trials (61 of 413 trials) and
10% of CNS trials (30 of 309 trials). The percentage
of trials involving biomarkers, relative to all trials
(including any for efficacy, toxicity, pathogen,
pharmacogenomics (PGX)/stratification, and PGX
identification/evaluation) that attained primary
outcome for oncology was 46%, for AI was 42% and
for CNS was 32%.
Given the significant biomarker involvement in
oncology trials, an analysis on study drug strategies,
and biomarkers to enable patient preselection and
stratification or that are used to help assess efficacy
was undertaken. For trials with all drugs, a larger
number of trials hit primary endpoint. For the subset
of these trials that involved any biomarker type,
again more trials hit endpoints compared to the
other outcome categories (Figure 4A). This same
trend was evident for the data set involving PGX/
patient stratification biomarkers as well as for trials
with efficacy biomarkers.
For the trial set with novel study drugs (Figure 4B),
the absolute numbers of trials that hit primary
endpoint was higher than each of the other
outcome categories for all trials, all biomarker
trials, PGX/stratification biomarker trials, and
efficacy biomarker trials. For the set of trials with
study drugs tagged as label-extension, the trend
seen across all trials and novel drug trials persists
(Figure 4C). Of note is the fact that trials involving
any biomarker type comprise more than 50% of all
positive outcome trials for all drug strategy trials
(63.7%), novel study drugs (58.3%) and for label
expansion (65.1%). Among the subset of PGX/
stratification biomarker trials, 57% hit endpoint;
for the novel strategy trial set, 65.7% hit endpoint,
while the label-expansion had an average of 51.7%.
Efficacy biomarker trials had slightly higher success
rates: 64% for all strategies; 74.2% for novel study
drug; 63.8% for label-expansion.
Biomarker Effectiveness

21. April 2017 / 21© Informa UK Ltd 2017 (Unauthorized photocopying prohibited.)
Fig. 4C Oncology Phase II through III/IV outcomes for label-expansion trials
Source: Trialtrove, February 2017
100
80
60
40
20
0
TrialCount
Negative outcome/
primary endpoint(s)
not met
Outcome
unknown
Outcome
indeterminate
Positive outcome/
primary endpoint(s)
met
All trials (194) Biomarker (125) PGX/Strat (71) Efficacy (85)
30 26
49
89
23 14
30
58
13 11 17
30
18 10 20
37
Fig. 4A Oncology Phase II through III/IV outcomes for all drug strategies
200
150
100
50
0
TrialCount
Negative outcome/
primary endpoint(s)
not met
Negative outcome/
primary endpoint(s)
not met
67
49
98
179
50
28
60
114
23
14
34
65
42
24
38
73
Outcome
unknown
Outcome
indeterminate
Positive outcome/
primary endpoint(s)
met
All trials (393) Biomarker (252) PGX/Strat (136) Efficacy (177)
Positive outcome/
primary endpoint(s)
met
Efficacy (67)
60
21
35
12
23
Fig. 4B Oncology Phase II through III/IV outcomes for trials with novel drugs
70
60
50
40
30
20
10
0
TrialCount
Negative outcome/
primary endpoint(s)
not met
Outcome
unknown
Outcome
indeterminate
All trials (130) Biomarker (84) PGX/Strat (43)
26
12
32
20
87
18
8
15
26
1

22. 22 / April 2017 © Informa UK Ltd 2017 (Unauthorized photocopying prohibited.)
Terminated 2016 Clinical Trials
Among the 603 terminated trials, a mere 13 were
stopped due to early demonstrated efficacy. Across
all 603 trials, 25% were in Phase III and 40% in
Phase II. The higher Phase II number suggests that
companies are making the decision to stop a trial,
and in certain cases, a development program at
Phase II. This supposition is supported by the fact
that the largest trial count is for trials terminated
due to a business decision (Table 14). These
business decisions range from a company’s stated
pipeline reprioritization, drug strategy shift or other
corporate stated reason.
By volume, Oncology trials accounted for 50%
of total trials; of these, 60% (180/300) were
terminated at Phase I/II and II. AI and Infectious
Diseases saw 50% of their Phase I/II and II trials
terminated, while CNS and Cardiovascular saw 43%
and 39%, respectively, of their trials terminate at the
same phases (data not shown).
The sponsors with 20 or more terminated trials
and the reasons for termination are listed in Table
15. Novartis leads the group, with 41% of the trials
stopping due to either lack of efficacy or significant
safety issues. AstraZeneca (AZ) and Pfizer are the
clear leaders in terms of stopping trials due to
business strategy, with 42% and 46% of their trials,
respectively.
Table 14. Trial termination reason by phase*
Table 15. Sponsors with over 20 trials terminated in 2016
* Trials do not include those stopped early due to efficacy Source: Trialtrove, February 2017
Source: Trialtrove, February 2017
Termination Reason I I/II II II/III III Total
Terminated, Poor enrollment 22 9 53 2 21 107
Terminated, Lack of efficacy 7 12 42 4 31 96
Terminated, Business decision - Other 41 26 63 4 49 183
Terminated, Safety issues 16 12 22 1 10 61
Terminated, funding issue 1 1 5 1 1 9
Planned, but not initiated 5 1 9 1 11 27
Terminated, unknown/other 39 14 45 4 23 125
Sponsor Total trials Business Decision Efficacy Enrollment Safety
Novartis 49 10 9 11 11
Pfizer 35 16 5 4 4
Roche 26 6 3 8 --
AstraZeneca 24 10 3 3 2
Merck Co. 22 5 4 4 1
Bristol-Myers Squibb 21 5 1 9 2

23. April 2017 / 23© Informa UK Ltd 2017 (Unauthorized photocopying prohibited.)
Half of the terminated trials were oncology trials
(300), and of these, NSCLC numbered 96. Within this
therapy area, NHL, breast cancer, melanoma and
prostate cancer rounded out the top five diseases
and accounted for 225 trials. Of note, however,
is for each of these diseases, industry sponsors
terminated the lion’s share of their trials at Phase
II (data not shown). Oncology led the way in “kill
early” overall with 82.7% of all trials stopping at
or before Phase II. For cancer trials, Phase I trials
enroll patients with some type of cancer and some
efficacy endpoint is often included in the trial design,
so earlier efficacy signals can be seen compared
with Metabolic/Endocrinology and Cardiovascular
which had the lowest percentages of early phase
terminations, at 55.9% and 57.1%, respectively.
Closing Thoughts
If a report card for 2016 completed trials were
to be graded, industry would receive a C+ based
on trials achieving success. But this is not really
a fair assessment, since 55% of all the trials had
not reported outcomes as of February 13, 2017.
Another metric that can be evaluated is that of
industry’s appetite to terminate trials early, and
the numbers suggest that the grade should be
elevated to at least a B+. But the CNS area lagged
behind oncology and AI on the metric, prompting
the question of what are companies in this space
not doing? Twenty-one of the 31 trials terminated at
Phase III were for movement disorders, Alzheimer’s
disease, epilepsy and nociceptive pain (related to
osteoarthritis). For the latter disease, JJ was the
sole industry sponsor. Might it be the case that given
the lack of big winners this therapeutic area in the
past, sponsors are taking bigger gambles and letting
clinical programs move to Phase III in hopes of
seeing some signal for symptom relief, if not disease
modification or slowing of disease progression?
An alternative metric is innovation, using as a proxy
the novel study drug designation. Across the data
set, novel drugs represented between 41% - 51% of
early stage trials – a healthy pipeline of innovation
by developers, supporting a letter grade of B at the
very least.
As discussed above, CNS had the fewest trials
involving novel study drugs. Past failures have
plagued this therapeutic domain and one would
expect that few of these novel candidates will
survive through Phase III. But should the past trend
reverse, the market would be in for significant
disruption. A recent Pink Sheet raised this issue with
Biogen’s aducanumab, seen as a potential time
bomb for health budgets.1
But novelty, while important, should not be
considered without the lens of companies’ efforts to
increase their drug franchises, and for 2016 industry
sponsors fared well. Across all of the oncology, AI
and CNS trial set, the percentage of trials hitting
primary endpoint for trials involving label expansion
ranged between 30 – 46%. For oncology, across all
trials, the success rate was nearly 50%, with Phase
II trials contributing over 70% of those successful
trials. For AI, of the 53 trials that succeeded, 70%
were in Phase III.
A prime example of a successful franchise expansion
is the FDA’s recent approval of AbbVie’s Humira
(adalimumab) for inclusion of moderate-to-severe
fingernail psoriasis data in prescribing information
for patients with moderate to severe chronic plaque
psoriasis. AbbVie claims to be the sole biologic with
this label inclusion. But biosimilars are knocking at
Humira’s door, and 2016 saw the completion of
ten biosimilar trials of which three were Phase III
trials. A recent Scrip article summarized a series of
interviews with US payers and reported that many
insurers are more focused on starting new patients
immediately on biosimilars rather than switching
patients stabilized on branded biologics.2
Finally, the relatively small magnitude of use of
pharmacogenomic screening to select or stratify
patients for oncology trials was a bit surprising.
Personalized medicine strongly relies on genomic
screening, and the increase in this biomarker use in
trials was recently documented in a recent Informa
Pharma analysis 3
, although the proportion of trials
started using PGX biomarkers declined between
2015 and 2016. Is the snapshot data for 2016
merely an anomaly, or is there a changing trend?
Only time will tell.
5 Informa’s Pink Sheet https://pink.pharmamedtechbi.com/PS120356/Aducanumab-Seen-As-Potential-ALS-Time-Bomb-For-Health-Budgets
6 Informa’s Scrip https://scrip.pharmamedtechbi.com/SC098402/Payers-Want-Deep-Discounts-To-Make-Biosimilars-Worth-Their-While
7 Informa Pharma Intelligence In Vivo recent analysis: Once Size No Longer Fits All, The Personalized Medicine Trial Landscape https://invivo.
pharmamedtechbi.com/IV005051/One-Size-No-Longer-Fits-All-The-Personalized-Medicine-Trial-Landscape

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