Drug Discovery

Discovery Today
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Volume xxx, Number2xxd February
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PERSPECTIVE

FEATURE
Feature
Small biotechs versus large
pharma: Who drives first-in-class
innovation in oncology?
⇑
Kate H. Kennedy 1, Krisstel Gomez, Natalie J. Thovmasian, Dennis C. Chang

There is a narrative that large pharma relies on biotech and academia for drug innovation. We tested

Features  PERSPECTIVE
this thesis by identifying the originators of all 50 first-in-class (FIC) oncology drugs that were approved
by the FDA from 2010 through 2020. Overall, the numbers support the narrative: large pharma was the
sole originator of only 14% of FIC cancer drugs, whereas small biotechs originated 46%, and academic
labs 14%. However, origins tell an incomplete story: large pharma companies launched or were
involved in launching 76% of FIC cancer drugs. Moreover, three of the five top-selling FIC oncology
drugs had large pharma origins. Thus, although biotechs and academia do originate more drugs, large
pharma remains important in shepherding drugs through clinical development and approval, and in
originating high-impact novel therapies.

Keywords: Biopharmaceutical R&D; drug development; cancer; oncology

Large pharma companies have historically
driven drug discovery and development,
but over the past decade or so, they have
frequently been criticized for being
increasingly ineffective in their core inno-
vation mission. Critiques often mention
disproportionate investment in marketing
rather than research, excessive focus on
‘me-too’ products, or monopolistic and
exploitational behaviors. The central
claim, however, is that innovative drug
discovery is now largely driven by small
biotech companies and academic labs,
and that large pharma companies rely on
buying or partnering with small startups
in order to sustain their portfolios [1,2].
This narrative rings true in light of the
impressive growth of the Boston/Cam-
bridge and other biotech hubs over the
past two decades. It is worth noting, how-
ever, that those years have seen tremen-
dous activity in the biopharmaceutical
industry overall. This is particularly true
in oncology, where the FDA approved
more than ten new drugs per year on aver-
age between 2010 and 2020, more than
double the rate in the previous decade.
Could this have occurred without substan-
tial discovery work by large pharma? More-
over, the top-selling oncology drug
today—the PD1 inhibitor Keytruda (pem-
brolizumab)—was discovered by Organon,
which was a reasonably large pharma com-
pany even before its acquisition by
Schering-Plough (and the subsequent mer-
ger with Merck) [3]. Is this just an outlier,
or does large pharma still play a major role
in originating novel drugs? More broadly,
what are the relative contributions of small

1
Kennedy, K.H. is no longer affiliated with Clarion Healthcare.

1359-6446/Ó 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
https://doi.org/10.1016/j.drudis.2022.103456 www.drugdiscoverytoday.com 1
 PERSPECTIVE
and large pharma companies and of acade-
mia to therapeutic innovation?
Originators of the first-in-class oncology
drugs approved between 2010 and 2020
To address this question, we tracked down
the originators of all of the first-in-class
(FIC) new molecular entities and biologics
that gained FDA approval for oncology
indications in the past decade (2010–
2020, n = 50) through a comprehensive lit-
erature search. We focused specifically on
oncology as a test case for drug innova-
tion, given that oncology is the highest-
sales therapeutic area in the biopharma
sector (and still fast growing) and is also
the area with the largest development
pipeline. We defined the originator as the
entity (or entities, if in collaboration) that
first isolated the drug compound or bio-
logic molecule in the approved therapeu-
tic. A therapy was considered FIC if it was
the first approved drug or biologic of its
type (small molecule, antibody, anti-
body–drug conjugate and so on) for a
specific molecular target. We classified
the originator as academic or industry,
and within the industry originators, we
categorized biopharma companies with
1–1000 full-time employees at the time of
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discovery as ‘small’, those with 1,000–
10,000 employees as ‘medium’, and those
with more than 10,000 employees as
‘large’. We defined the year of discovery
as the first documented mention of the
Drug Discovery Today
FIG. 1
A. Originators of the 50 first-in-class (FIC) oncology drugs approved by the FDA from 2010 to 2020. Originators were classified by company size or as
academic or as a collaboration involving more than two entities. Companies that had 1–1000 full-time employees at the time of discovery were considered
small, 1000–10,000 employees medium, and more than 10,000 employees large. B. Breakdown of the originator types involved in the 11 collaborations.
2 www.drugdiscoverytoday.com
Drug Discovery Today
drug candidate, as identified through a
comprehensive literature search.
Our findings show that, in terms of
absolute number of drug discoveries, small
pharma is the clear winner, as the sole
originator of more than three times as
many FIC-approved drugs as large pharma
(46% vs. 14%) (Fig. 1). These small-
pharma-originated drugs include transfor-
mative therapies such as the Bruton's tyro-
sine kinase (BTK) inhibitor ibrutinib
(Imbruvica, originally from Celera), the
anti-CD38 monoclonal antibody daratu-
mumab (Darzalex, from Genmab) and
the poly (ADP-ribose) polymerase (PARP)
inhibitor olaparib (Lynparza, from KuDOS
Pharmaceuticals). When including collab-
orative discoveries, small pharma or bio-
tech companies were involved in
originating 62% of all drug discoveries (as
the sole or co-originator), versus only
26% for large pharma, and 8% (four cases)
for medium pharma.
Role of academia and collaborations in
drug discovery
Remarkably, the number of drugs that
originate from academic research alone
was on par with that originated by large
pharma (each 14% of our sample). Note
that these ‘origins’ do not refer to the dis-
covery of a target, mechanism, or path-
way—which are traditionally the purview
of academic research—but to the discovery
or creation of the therapeutic compound
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itself. This finding further highlights how
far large pharma has fallen from domi-
nance in drug discovery, as academic labs
have more limited financial resources than
large companies and typically are not
focused primarily on drug discovery. Fur-
thermore, some of these academia-
originated therapies are among the most
significant advances of the past decade,
including the first-ever approved chimeric
antigen receptor (CAR) T-cell therapy, tis-
agenlecleucel (Kymriah) for B-cell malig-
nancies (University of Pennsylvania), and
the multi-billion dollar prostate cancer
endocrine therapy, abiraterone acetate
(Zytiga, originated at the Institute of Can-
cer Research [UK]).
Furthermore, focusing on the drugs
that originated solely from academic labs
probably underestimates the impact of
academic-led research on drug innovation,
for three key reasons. First, academia also
contributed substantially to innovative
drug discovery through collaboration with
industry. Of the 11 drugs in our sample
that originated through collaborations of
two or more entities, seven (64%) involved
academia. Second, many small biotech
companies are founded by academic scien-
tists who leave academia to head up their
own companies. In fact, 60% of the small
pharma originators in our sample had at
least one (co)-founder who had previously
held a tenure-track university position.
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Drugs that originated from small biotech
companies with at least one (co)-founder
who left academia include blockbusters
such as the BTK inhibitor ibrutinib, the
PARP inhibitor olaparib, and the CTLA-4
inhibitor ipilimumab.
Third and finally, there are also many
ways in which academia collaborates with
industry that are not formally documented
in this analysis. We did not account for the
role that informal cross-pollination of
ideas and capabilities across organizations
may have played in drug discovery and
development. For example, the CDK4/6
inhibitor Ibrance (palbociclib) was initially
discovered by Pfizer, so the originator is
categorized as large pharma. However,
the development of Ibrance was halted at
one point, and it was not until academic
research showed promising preclinical
and clinical results that Pfizer re-invested
in developing Ibrance, eventually leading
to drug approval in 2015. Similarly, aca-
demic researchers also played a key role
in realizing the potential of Imbruvica
(ibrutinib). This type of informal collabo-
ration and knowledge sharing is prevalent
and plays a key role in ensuring that trans-
formative discoveries are translated into
products that can improve patient out-
comes, both within and outside academia.
In the case of Keytruda, Merck was
inspired by competitor data from another
large pharma company, Bristol-Myers
Squibb (Table 1).
When industry was involved in collab-
orations, small pharma was the most
active company size, participating in
eight of 11 (73%) collaborative FIC drug
discoveries, whereas large pharma partici-
pated in six (55%) and medium pharma
in two (18%). Most of the drug discover-
ies that resulted from small pharma col-
laborations occurred in partnership with
large pharma (five of eight). Examples
of FIC drugs that have originated from
collaborations between small and large
pharma include ado-trastuzumab emtan-
sine (Kadcyla, from Immunogen/Genen-
tech) and vismodegib (Erivedge, from
Curis/Genentech/Evotec). Overall, collab-
orations were more common in locations
that are considered to be biotech and
pharma ‘hubs’ (Boston, San Francisco,
and San Diego), suggesting that geo-
graphical proximity potentially facilitates
collaboration.

TABLE 1
More than origins: collaborations and external insights drive key decisions in drug development.
Drug
[Mode of action, Peak revenue
through 2022]
Keytruda (pembrolizumab)
[Inhibitor of PD1, $19.5B]
Brief summary of origin and development history Reference
Originated by large biopharma: Organon [3]
External insight provided by a competitor large pharma: BMS
The Dutch pharma company Organon started a PD1 drug discovery program in Oss in 2003 under
Andrea van Elsas; the program was transferred to a 20-person team in Cambridge, MA in mid-2005.
Pembrolizumab was discovered by that team. After Organon was acquired by Schering-Plough in 2007,

Imbruvica (ibrutinib)
[Inhibitor of BTK, $8.9B]
Ibrance (palbociclib)
[Inhibitor of CDK4/6, $5.7B]
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however, the PD1 program was relegated to ‘low priority’. Then, after Schering-Plough merged with
Merck, the program was halted. It wasn’t until Bristol Myers Squibb reported promising data with their
PD1 inhibitor, nivolumab, that Merck re-invigorated the program, raced to catch up and ultimately
leapfrogged BMS to gain the first approval for a PD1 inhibitor in 2013, for second-line treatment of
metastatic melanoma.
Originated by small biopharma: Celera [4]
External insight provided by academic research: Stanford University (Ronald Levy)
Celera was originally a genomics company, founded by J. Craig Venter in 1998 and famous for
outpacing government efforts to sequence the human genome. In the early 2000s, the company
initiated drug discovery programs, one of which focused on Bruton’s Tyrosine Kinase (BTK), a key
protein in B-cell receptor (BCR) signaling. This team developed ibrutinib as a ‘tool’ compound to aid in
screening BTK inhibitor (BTKi) drug candidates for autoimmune diseases. However, ibrutinib showed
more potential than any of the candidates from the screens. In 2006, Celera sold its drug discovery
programs to Pharmacyclics, another small biopharma company. Co-founder Dr Richard Miller was
interested in assessing the BTKi (then called PCI-32765) in B-cell malignancies, encouraged by visits to
Ronald Levy’s lab at Stanford, where BCR pathway inhibition was a main focus. Imbruvica gained its first
approval in 2013 for relapsed or refractory mantle cell lymphoma patients.
Originated by large biopharma: Pfizer [5]
Insight provided by academic research collaboration: UCLA (Dennis Slamon, Richard Finn)In 1995,
researchers at Parke-Davis, a large pharma company and subsidiary of Warner-Lambert, initiated a drug
discovery program focused on cyclin-dependent kinases 4 and 6 (CDK4/6). Pfizer acquired Parke-Davis/
Warner Lambert in 2000, and palbociclib (then called PD-0332991) was subsequently synthesized in
2001. The program was halted due to: 1) poor data from clinical trials of other CDK inhibitors; 2) internal
competition for resources from pipeline programs that Pfizer had acquired from Pharmacia in 2003; and
3) the weak efficacy of Palbociclib monotherapy in an all-comers solid tumor phase 1 trial. However,
Pfizer continued to provide the compound to academic investigators as a research tool. One such
researcher, Dennis Slamon at UCLA, discovered that ER+ breast cancer cell lines were sensitive to the
drug, and then he and colleague Richard Finn conducted a small clinical study with ER+ breast cancer
patients, which showed promising results. This motivated Pfizer to resurrect the program in 2009 and to
start a phase 2 trial in breast cancer patients. Palbociclib obtained its first FDA approval in February
2015.

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 PERSPECTIVE
Varying roles for large Pharma and
biotechs across the drug development
cycle
The findings reported above support the
narrative that small biopharma companies
outperform large pharma in terms of the
number of FIC drugs discovered. Acade-
mia, too, has a larger role in originating
drugs than has been recognized histori-
cally. Nevertheless, focusing on the origi-
nators of drugs alone does not account
for the important roles played after the
drug is discovered. Furthermore, focusing
only on numbers of drugs does not
account for differences in the impacts of
those drugs.
In probing the first point, we found
that the contributions of small and large
pharmaceutical companies shift drastically
over the course of drug development.
Although large pharma was involved in
the origination of only 26% of FIC cancer
drugs (14% as sole originator), large
pharma owned or co-owned 76% of the
drugs by the time of launch (Fig. 2A).
Thus, while the origination of FIC drugs
may occur more often in small pharma or
academic labs, large pharma remains the
dominant player in later drug develop-
ment and commercialization.
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The journeys taken between discovery
and launch vary widely (Fig. 2B). For the
23 FIC cancer drugs originated by small
pharma, in eight cases (35%), the small
pharma company was eventually fully
acquired by a large pharma company. In
three cases (13%), the small biopharma
company licensed worldwide rights to the
development and commercialization of
the asset to a large pharma company. In
one case (4%), the small pharma originator
retained the US rights but licensed ex-US
rights to large pharma, and in two cases
(9%), the small pharma company co-
commercialized the drug in the US with a
large pharma partner. In five other cases
(17%), the small pharma company
licensed the asset to a different small
pharma entity, but in four of those cases,
the new small pharma owner then part-
nered with medium or large pharma com-
panies for commercialization. There were
only four cases (17%) in which the small
pharma company that discovered the drug
also completed the development and
launch of the drug.
For the drugs that started with small
pharma or academia but ended up with
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Drug Discovery Today
large pharma, the large pharma company
typically led and funded clinical develop-
ment. Thus, while large pharma may reap
benefits from small biotech’s discoveries,
they also incur much of the financial costs
and risks of clinical programs and bring
crucial capabilities for launching the
drugs. However, there are also examples
where the small pharma company or aca-
demia conducted first-in-human trials of
the FIC drug (e.g., Xencor for tafasitamab
(Monjuvi), NCI for dinutuximab [Uni-
tuxin]), or were involved with a portion
of development costs (e.g., PDL Bio-
pharma agreed to fund 20% of the devel-
opment costs of elotuzumab [Empliciti]).
There are other examples where the small
biotech built up their commercial func-
tions and launched drugs directly (e.g.,
Dendreon, Agios, Karyopharm, Epizyme).
Impact of FIC oncology drugs discovered
by large vs small pharma
Beyond looking at the numbers of FIC
drugs discovered by different entities, we
also sought to assess the impact of these
drugs. As a rough but simple metric, we
assessed the annual peak or maximal rev-
enue for each drug from 2010 through
2022—looking at actual sales data from
2010–2021 and sales forecasts for 2022
from consensus analyst reports obtained
from Evaluate Pharma—and calculated
the percentage of sales attributable to each
originator class. The premise is that the
drugs that have the highest sales tend to
have the highest utilization, which corre-
lates with at least their perceived clinical
impact or value. We acknowledge that rev-
enue is an imperfect proxy for clinical
value, given that additional factors (such
as pricing, geographic expansion, and mar-
keting) also impact drug sales. Nonethe-
less, our findings show that FIC cancer
drugs originated by large pharma tend to
have a larger impact than those originated
by small pharma.
When examining total peak sales across
the 50 FIC drugs, we found that the FIC
oncology drugs that were originated solely
by large pharma account for 44% of peak
sales, compared with 40% of peak sales
for drugs originated by small pharma
(Fig. 3A). This difference is particularly
impressive when we consider that large
pharma companies discovered only
around a third of the number of assets that
small pharma discovered (14% vs. 46% of
d Volume 28, Number 2 d February 2023
our sample, respectively). On average, the
drugs in our sample that were discovered
by large pharma generated approximately
3.6 times the revenue of drugs discovered
by small pharma. Although analyst fore-
casts through 2026 suggest that this gap
will close slightly in the future, the drugs
that originated from large pharma would
still, on average, generate approximately
three times the revenue of small-pharma-
originated drugs.
What accounts for this wide disparity in
impact? We considered the possibility that
there is an outlier effect, given that the
top-selling drug in our list, pembrolizumab
(Keytruda), was discovered by large
pharma (Organon) and has revenues far
above those of any of the other FIC drugs,
with 2022 sales estimated at $19.5B; the
second-highest revenue (from ibrutinib)
was $8.9B. When we looked at a histogram
view of product sales by originator
(Fig. 3B), however, it became clear that
Keytruda’s exceptionally high sales do
not explain the difference in the impact
of drugs originated by small pharma vs
large pharma. Of the seven FIC cancer
drugs originated solely by large pharma,
the majority (four of seven, or 57%) were
‘blockbusters’ (peak sales $1B), whereas
only a minority of FIC drugs originated
by other entities had such high sales. For
FIC drugs with small pharma as the sole
originator, only five of 23 (22%) had
blockbuster-level sales, and for all other
FIC drugs, there was a similar rate of drugs
with blockbuster-level sales, three of 20
(15%). The median peak sales revenue for
large-pharma-originated FIC drugs was
over eight-fold higher than that for
small-pharma-originated drugs, a much
larger difference than that between the
means, even though the median is not as
sensitive as the mean to the magnitude
of Keytruda’s sales.
It was also apparent from our analysis
that small pharma and biotech companies
have certainly been capable of discovering
high-impact therapies. When we exam-
ined the top-selling products in our sam-
ple, we found that large pharma was the
originator of the #1 and #4 products: Key-
truda, as discussed above, and the CDK4/6
inhibitor palbociclib (Ibrance), which was
discovered by Pfizer and which has $5.7B
in estimated sales for 2022. However, small
pharma was the originator of the #2 and
#3 products: ibrutinib (Imbruvica), discov-
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Drug Discovery Today

FIG. 2
Entities involved in the discovery and development of first-in-class (FIC) oncology drugs as originators and at launch. A. Large pharma involvement at
drug discovery and launch for 50 FIC oncology drugs approved by the FDA from 2010 to 2022. The ‘Other licensing agreement with Large Pharma’ category
includes US co-promotion with large Pharma and ex-US rights licensed out (while US rights are retained). Among the assets with global rights out-licensed to
large pharma, there are three that involve collaborations with small pharma. B. Status of drug licensing at the time of launch by type of originator. For US co-
commercialization with large pharma, ex-US rights were out-licensed to large pharma. One spin-off company created by academic drug originators was
acquired by large pharma. For collaborations involving small pharma, the companies owning the drug were acquired by large pharma late in the drug
discovery process.

ered by Celera, at $8.9B in estimated 2022
sales, and daratumumab (Darzalex), dis-
covered by Genmab, at $7.2B in estimated
2022 sales. Thus, both large and small
pharma originated top-selling drugs.
Another possibility that we considered
was whether the commercial capabilities
of large pharma companies drove higher
sales, given that large pharma companies
launched all the large-pharma-originated
drugs vs only a majority of drugs origi-
nated by other entities. Large pharma has
more resources for commercialization than
smaller companies, including bigger bud-
gets and larger teams for marketing and
field promotion. To address this possibil-
ity, we focused on the subset of 38 FIC
drugs that were launched with large
pharma involvement (Fig. 3B). When we
compared the drugs originated solely by
large pharma to the drugs originated with-
out any large pharma involvement, the
effect remained strong: median peak sales
for large-pharma-originated drugs was still
about six-fold higher. However, when we
considered the drugs that originated with
large pharma involvement—pooling the
large pharma sole-originator group with
the group of drugs from collaborations
involving large pharma—the effect was
much attenuated: median peak sales rev-
enue was only 1.5-fold higher than that
for the group of drugs with no large
pharma involvement. We see two plausi-
ble explanations for this finding. The first
is that the high sales seen for drugs that
have large pharma as their sole-originator
is actually an artifact of the small sample
size, which is partially corrected by the
pooled additional data points. Another
explanation, however, is that the sales dif-
ference is real, and that the discovery and/
or development of the collaboration-based
drugs may be more akin to those of small
pharma/academia-originated drugs; thus,
it would be inappropriate to pool
collaboration-based drugs with the large
pharma sole-originator drugs. For exam-
ple, when large pharma partners with an
academic lab or small pharma for drug dis-
covery, it might be that the decision-
making processes is heavily swayed by
the academic/small pharma stakeholders,
and/or that the fruits of those partnerships
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are not reviewed as stringently because of
bias resulting from the effort that went
into forming the partnership in the first
place or from the fear of negative investor
reactions if the partnership flounders.
Ultimately, we cannot explain defini-
tively why large-pharma-originated FIC
drugs have such an outsized impact. Our
analyses showed consistently that large
pharma involvement at launch was associ-
ated with higher sales, but also that large
pharma involvement in drug origination
was associated with higher sales, although
the small sample size limits our ability to
discern the relative strengths of those asso-
ciations. It may be that the commercializa-
tion capability advantage of large pharma
(together with the small sample size of
our study) explains a large portion of the
difference in the impact of drugs origi-
nated by small pharma vs large pharma,
but there may be other important factors.
We hypothesize that if the drug devel-
opment process is pictured as a funnel
(many candidates start but few reach
approval and launch), the differences in
drug impact could arise due to factors at

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Drug Discovery Today

FIG. 3
Revenue generated by first-in-class (FIC) oncology drugs. A. Peak sales for each product were defined as the highest revenue in a calendar year from
launch through 2022. Actual sales data were used for 2010–2021; 2022 revenue is an analyst consensus forecast from Evaluate Pharma. Companies were
classified in the same manner as for Fig. 1. B. Count of assets by peak revenue and by originator type. The first three graphs show the counts for all assets
associated with each originator category, and the last three graphs show the counts for assets launched by or in partnership with large pharma. All of the
assets solely originated by large pharma were launched by large pharma.

the ‘top of the funnel’ or in the ‘funnel reluctant to terminate a program, even if only on drugs that had successfully passed
itself’, or a combination of the two. The early clinical data or shifting competitive through the funnel. To assess how much
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‘top of the funnel’ explanation would be
that large pharma has a greater focus on
high-impact opportunities at the outset,
and focuses drug discovery efforts accord-
ingly. In this hypothesis, drug discovery
teams generally follow the science, but
within large pharma companies, those
teams will receive more input from com-
mercial and clinical strategy stakeholders,
which will steer efforts towards areas with
larger patient populations and greater
unmet need and, conversely, away from
smaller niche opportunities. By contrast,
small pharma and academia collectively
cast a wider net, and thus feed the ‘funnel’
with a broader pool of candidates.
The ‘funnel itself’ hypothesis has two
elements. The first is that large pharma
may prioritize drugs more stringently over
time. Larger organizations tend to have
more gatekeepers and processes for making
go/no-go decisions in development pro-
grams than smaller companies. Thus, even
with an equally broad set of candidates at
the top of the funnel, large pharma com-
panies may, over time, narrow these candi-
dates down to a smaller, higher-impact set.
By contrast, small companies may be more
dynamics suggest limited impact, espe-
cially when a small company is built
around a single asset or a small number
of assets. The second possibility is that
large pharma has the resources to fund tri-
als across a larger array of potential indica-
tions and geographies, which may increase
the utilization of a product at the end of
the discovery process. The idea here is that
blockbusters are ‘built, not born’: after
homing in on those programs that have
the greatest clinical and commercial
potential, large pharma companies can
then invest more substantially in develop-
ment to maximize their value. The prod-
ucts that come out of a large pharma
funnel tend to have a stronger dataset to
support their adoption and uptake. The
contribution of this is offset, however, by
the fact that many drugs that are origi-
nated by small pharma companies or aca-
demia are acquired by large pharma in
early phases and are supported by large
pharma development investments
thereafter.
Additional research and analysis are
needed to resolve which of these hypothe-
ses predominate. Our current work focused
of a difference already existed at the top
of the funnel, and how much of the differ-
ence arose as the drugs passed through the
funnel, one would need to assess the
broader set of ‘failed’ drugs at different
stages. This is a much larger set of drugs,
and many are more difficult to track. The
current study does show that among the
FIC oncology drugs that have been
approved and launched, only a minority
originated in large pharma labs, but those
that did have had an outsized impact.
Conclusions
Our assessment of the origin stories of FIC
oncology drug provides new insight into
the contributions of industry to oncology
innovation. We found that the recent nar-
rative extolling the capabilities of small
biotech—and critiquing the drug discov-
ery output of large pharma—does have a
kernel of truth: small companies were
much more prolific in discovering FIC can-
cer drugs. Furthermore, academic labs were
the sole originator of as many FIC drugs as
large pharma, and also played a key role in
spawning the many discoveries of small
biotechs.

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Drug Discovery Today d Volume 28, Number 2 d February 2023
Nonetheless, large pharma does play a
crucial role in shepherding discovered
drugs through clinical development and
ultimately approval. Furthermore, collabo-
ration between small and large pharma in
originating drugs is not uncommon, and
continued collaborations and interactions
among different types of stakeholders can
be critical for realizing a drug’s potential.
Moreover, we found that the FIC cancer
drugs that have been originated by large
pharma have had a disproportionate
population-level impact, as measured by
annual sales. We have discussed several
potential explanations for this outsized
impact, but further analysis is needed to
test these ideas and to refine our under-
standing of drug discovery.
One direction for future studies is to go
beyond outputs and dig deeper into inputs
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in drug discovery and development pro-
cesses. Our focus was on successful discov-
eries—those that achieved FDA approval—
whereas the effectiveness and/or produc-
tivity of drug discovery should also
account for the success rate, R&D spend,
speed, and human capital expenditures.
This analysis would speak to not just to
which originator type is the most prolific,
but also to which is most productive and
efficient. Expanding the analysis beyond
oncology would increase the sample size
and account for potential variation in mar-
ket dynamics across therapeutic areas. In
addition, our sample focused on FIC drug
discoveries as a proxy for innovation, but
there are plenty of examples in which
second- or even third-generation drugs
have had transformative clinical impact
for patients. For example, the third-
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[4] Shaywitz, D. (2013) The wild story behind a
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PERSPECTIVE
generation epidermal growth factor recep-
tor (EGFR) inhibitor osimertinib (discov-
ered by AstraZeneca, a large pharma
company) has greatly improved survival
for EGFR-mutated non-small cell lung can-
cer patients. Looking forward, these types
of analyses will be crucial in providing a
better understanding of how different
players contribute to the endeavor of dis-
covering and developing better medicines.
Data availability
Data will be made available on request.
Declaration of Competing Interest
During the writing of this article, the
authors were employees of Clarion Health-
care, LLC.
[5] Garber, K. (2014) The cancer drug that almost
wasn’t. Science. 2014;345:865–867. https://doi.org/
10.1126/science.345.6199.865.
Kate H. Kennedy 1, Krisstel Gomez,
⇑
Natalie J. Thovmasian, Dennis C. Chang
Clarion Healthcare, Summer St, Boston, MA 02210,
Features  PERSPECTIVE
USA
⇑ Corresponding author: Chang, D.C.
www.drugdiscoverytoday.com 7