GlobalData estimates that the
value of the Non-Small Cell Lung Cancer (NSCLC) market in the 8 major markets
(8MM) in 2015 was $6.21B. This market is defined as sales of major branded
drugs commonly prescribed for NSCLC patients across the 8MM. Just over half of
these sales, $3.25B (52%), were generated in the US, with the 5EU representing
the next largest region by sales, estimated at $1.53B (25%). Japan and China
contributed the smallest proportions of sales to the global NSCLC market, with
2015 sales of $981M (16%) and $445M (7%), respectively.
By the end of the forecast
period in 2025, GlobalData projects NSCLC sales to rise to $26.8B in the 8MM,
at a moderate Compound Annual Growth Rate (CAGR) of 15.7%. In particular, GlobalData
expects the China NSCLC market to grow most rapidly, increasing to $4.3B (16%
of global NSCLC shares) by 2025 at a robust CAGR of 25.4%. Sales in the other
regions are also expected to increase by the end of the forecast period;
however, the proportion of sales from the US and Japan are forecast to decrease
to 26.9% and 22.3%, respectively, with market share in the 5EU increasing from
24.2% in 2015 to 34.3% by 2025.
MAJOR DRIVERS OF GROWTH
The increasing incorporation
of premium-priced immune checkpoint inhibitor immunotherapies into the NSCLC
treatment algorithm, particularly in the first-line setting, will be one major driver.
Merck & Co.’s Keytruda (pembrolizumab), Bristol-Myers Squibb’s (BMS’)
Opdivo (nivolumab), and Roche’s Tecentriq (atezolizumab), will all achieve
blockbuster status by the end of the forecast period. Collectively, immunotherapies
will reach $17.5B in sales by 2025, accounting for roughly 65% of total sales
in the NSCLC market. Of the $17.5B total, Keytruda, Opdivo, and Tecentriq are
projected to contribute $5.2B, $5.5B, and $2.8B, respectively.
Targeted therapies are also
expected to contribute to the growth of the NSCLC market. Overall, targeted
therapies will have sales of $9.4B by 2025, with AstraZeneca’s Tagrisso (os- imertinib)
and Roche’s Avastin (bevacizumab) having the highest sales of this drug class, followed
by Eli Lilly’s Cyramza (ramucirumab). Tagrisso is projected to achieve blockbuster
status by 2025, with $1.7B in estimated sales, reflecting a CAGR of 56.6% over
the forecast period. Its sales will be driven by its uptake in the second line and,
eventually, in the first-line setting in EGFR-mutant patients. Avastin sales
are expected to grow modestly from $1.3B in 2015 to $1.6B by 2025 at a CAGR of
1.9%, fueled by increased uptake in nonsquamous patients, but stunted by biosimilar
erosion that will occur in the 8MM over the forecast period, starting in 2018.
In fact, Avastin’s market share is sufficiently large that biosimilar
bevacizumab is expected to achieve $1B in sales by 2025, assuming it will be
priced at a 30% discount compared to branded Avastin. Cyramza sales are
expected to grow from $84M in 2015 to $613M in 2025 at a CAGR of 22%, driven by
launches in Japan and China.
The increasing incidence
of NSCLC in the 8MM will also drive growth. China, in particular, will see its
NSCLC incident cases increase significantly over the forecast period, at an
Annual Growth Rate (AGR) of 4.7%. Overall, across the 8MM, the incidence of
NSCLC is expected to increase at an AGR of 3.1% from 2015-2025. Growth in incidence
is forecast to be most pronounced in urban China, where GlobalData expects
there to be approximately 500,000 in 2025, rising from just over 330,000 cases
in 2015 at an AGR of 4.7%. This increase, coupled with an anticipated increase
in branded therapy prescriptions in China, will drive the growth of both the
Chinese and global NSCLC markets over the forecast period.
MAJOR BARRIERS OF GROWTH
Patent expiration of
several blockbuster drugs, including Tarceva and Alimta, will limit growth.
Tarceva, the leading epidermal growth factor receptor-tyrosine kinase inhibitor
(EGFR-TKI) in the NSCLC market, is expected to face patent expiry starting in
2016. GlobalData expects sales of the patented drug in the 8MM to decrease from
$783M in 2015 to $18M by 2025. Meanwhile, sales of generic erlotinib are
expected to reach $77M by 2025. In addition, sales of Alimta, which is commonly
used in combination with chemotherapy in nonsquamous patients, will decrease
from $2.1B in 2015 to $54M in 2025. Sales of generic pemetrexed are expected to
reach $266M by 2025. GlobalData anticipates the uptake of generics to
negatively impact the growth of the NSCLC market throughout the forecast period.
Pricing and reimbursement
difficulties encountered by premium-priced drugs, especially in the European
and Asian markets, are another major barrier. Increasing cost-consciousness
will limit premium pricing opportunities for pipeline agents in the NSCLC
market. Healthcare austerity measures are being incorporated across the major markets,
and drug companies will need to consider the changing reimbursement landscape
when determining pricing strategies for their drugs. GlobalData expects that
this era of austerity and healthcare reform will negatively affect
pharmaceutical companies’ ability to gain reimbursement approval for their new
NSCLC therapies, particularly immuno-oncology (IO) combinations that are
COMBINATION THERAPY IS THE MAIN
In 2015, the NSCLC market
was largely dominated by generic chemotherapy and targeted therapies, including
EGFR and anaplastic lymphoma kinase (ALK)-TKIs, accounting for approximately 94%
of the NSCLC market, while IO sales accounted for just 6%. In 2025, that trend will
be reversed, with 65% of the total NSCLC market going to IO therapies, and the
remaining 35% being split between chemotherapy and targeted agents.
A major trend in corporate
strategy is the pairing of programmed cell death protein 1 (PD-1) checkpoint
inhibitors with other agents. In the crowded PD-1 space, as drugs with
identical mechanisms of action (MOAs) are launched, companies are looking for ways
to boost efficacy in hopes of differentiating their product from that of their
competitors. As such, companies like Merck & Co., Roche, and BMS are
evaluating their PD-1 checkpoint inhibitors in combination with chemotherapies,
targeted agents, and/or other IO products. BMS has high hopes for the
combination of Opdivo + Yervoy (ipilimumab) in firstline therapy, while Merck
& Co. and Roche have focused on evaluating IO + chemotherapy combinations.
Roche is also investigating the combination of its programmed death ligand 1
(PD-L1) inhibitor Tecentriq + chemotherapy + Avastin in chemotherapy-naïve
nonsquamous NSCLC patients in the ongoing Phase III IMpower 150 trial.
Currently, BMS is the
market leader in the second-line setting, with Merck & Co. coming in second
due to the inconvenience of Keytruda’s label restriction hampering its uptake.
This ranking is not expected to change during the forecast period, as Opdivo
has a stronghold in the second-line setting. However, in the first-line setting,
due to Keytruda’s anticipated first-to-market advantage as a monotherapy in
PD-L1+ patients following Opdivo’s Phase III failure, GlobalData expects Merck
& Co. to become the market leader over the forecast period. Roche also has
a strong pipeline strategy, evaluating combinations of Tecentriq with
chemotherapies and/or targeted therapies in multiple Phase III trials that all
have the potential to lead to approval.
A FOCUS ON IMPROVING TARGETED THERAPY OPTIONS
In the targeted therapy
arena, companies are developing novel therapies for previously unactionable
mutations. KRAS mutants are an example of a patient subpopulation that makes up
a significant (25% to 30%) share of the total NSCLC patient pool, but for which
there are no targeted therapies currently available. Eli Lilly & Co.’s
pipeline agent abemaciclib targets KRAS patients, yet its lack of efficacy is
expected to severely limit its uptake, leaving opportunities for other KRAS
targeted therapies to enter the space. Recently, AstraZeneca’s selumetinib,
another KRAS targeted therapy, failed its Phase III trial, leaving the KRAS
mutant population without any effective late-stage pipeline drugs. In addition
to KRAS, BRAFV600E is also being explored as a target. This mutation has already
been successfully targeted in melanoma by the combination of Novartis’ Tafinlar
(dabrafenib) + Mekinist (trametinib), which is expected to make a big impact
for this patient population. However, the size of the eligible patient pool
will limit its sales to $318M for Tafinlar and $278M for Mekinist by 2025.
In addition to novel
therapies, companies are also developing second- and third-generation targeted
therapies to provide better options for patients with actionable mutations.
These newer targeted therapies commonly overcome resistance from
first-generation treatments, and/or have superior efficacy in certain
subpopulations. For example, AstraZeneca’s Tagrisso is effective in Tarceva/Iressa
(erlotinib/gefitinib)-resistant EGFR mutation positive (EGFRm+) patients, while
Roche’s Alecensa (alectinib) and Novartis’ Zykadia (ceritinib) have both been
reported to be effective in ALK mutation positive (ALKm+) patients with brain
metastases. GlobalData expects these next-generation targeted therapies to take
significant patient share away from their predecessors. Tagrisso is expected to
achieve sales of $1.7B by 2025, while Alecensa and Zykadia are expected to
achieve sales of $600M and $127M, respectively. All three drugs will have high CAGRs,
with Tagrisso being the highest, at 56.6%, followed by Alecensa at 24.5%, and
Zykadia at 13.3%. The sales of EGFRTKIs as a class will grow at a CAGR of 4.9%,
while the ALK-TKI sales will grow at a CAGR of 10.7%. Targeted therapies other than
EGFR- and ALK-TKIs are also expected to see significant sales growth, from
$1.5B in 2015 to $5.3B by 2025.
UNMET NEED IN THE NSCLC MARKET EXPECTED TO DECLINE
One of the main unmet
needs in NSCLC treatment is the need for more effective first-line treatment
options that provide overall survival (OS) benefits to patients with no
actionable mutations. Currently, the standard-of-care in the first line is
platinum-doublet chemotherapy, which has significant systemic toxicity and low
compliance rates. During the forecast period, PD-1 checkpoint inhibitors are
expected to launch in the first-line setting both as monotherapies and in
combination with chemotherapy or CTLA4 checkpoint inhibitors. With the entry of
these IO products, first-line treatment algorithms are expected to change, with
IO drugs expected to take a majority of patient share away from standard chemotherapies.
REMAINING UNMET NEED IS HIGHEST WHERE?
Although the current and
future IO drugs will significantly reduce unmet needs in NSCLC, there remains
high unmet need in the PD-L1-negative patient population. This population of
patients has been shown to receive minimal benefit from PD-1 agents thus far.
There has been some evidence that the combinations of IO + IO or IO + chemotherapy,
such as Opdivo + Yervoy and Keytruda + chemotherapy, respectively, may enhance
response rates in this patient pool, but the data are preliminary and need to
be confirmed in larger patient populations in ongoing clinical trials.
An opportunity remains for
drugs that target novel biomarkers/mutations in NSCLC. KRAS mutants, which
account for a significant portion (25% to 30%) of the total NSCLC patient population,
are the most underserved patient segment, with no currently available targeted
drugs. Further, there are also rare mutations that lack targeted therapies. For
example, NSCLC patients with the BRAFV600E mutation, which has already been
successfully targeted in melanoma, have no available targeted therapies at this
stage. During the forecast period, the unmet need for drugs targeting novel
biomarkers/mutations will decline with the entry of the first-in-class,
KRAS-targeting pipeline drug, Eli Lilly’s abemaciclib. For BRAFV600E-mutant
NSCLC, Novartis’ combination therapy of Tafinlar + Mekinist, which is already
approved to treat BRAFV600E+ melanoma, is expected to become available.
Despite the launch of
drugs addressing the unmet need in KRAS and BRAFV600E patients during the
forecast period, there remains opportunity for further development of targeted
therapies, particularly in squamous NSCLC. Since the mutations found in
squamous NSCLC are almost entirely distinct from well-described mutations, such
as EGFR and ALK that occur in nonsquamous disease, there is ample opportunity
for companies to develop targeted therapies against mutations associated with
squamous NSCLC. Some of these include PIK3CA amplification/mutation, FGFR1,
PTEN, and DDR2.
IMMUNO-ONCOLOGY DRUGS: RAPID UPTAKE
Roche’s Tecentriq is
expected to launch in combination with chemotherapy and/or Avastin in the
first-line setting for NSCLC. It is a “me-too” drug that will compete with
marketed products Opdivo and Keytruda, both of which are already approved in the
second line and are seeking label expansions into the first line. Projected peak-year
sales for Tecentriq are $2.8B. The majority of these sales will come from the
first line, but a small portion will also come from the second-line setting
once Tecentriq gains approval.
of durvalumab + tremelimumab is expected to launch in the first- and third-line
settings in NSCLC. This combination is one of two that pair a PD-1 inhibitor
with a CTLA4 inhibitor — the other being Opdivo + Yervoy. Projected peak-year
sales for durvalumab and tremelimumab are $1.7B and $1.1B, respectively.
Durvalumab + tremelimumab combination therapy is expected to lag behind
monotherapy and IO + chemotherapy combinations in uptake due to its high cost.
WHAT DO THE PHYSICIANS BELIEVE?
IO drugs are generating
excitement within the NSCLC community, as they provide a much-needed
alternative to chemotherapy in the second-line setting, especially for squamous
NSCLC patients. However, despite the enthusiasm for, and expected rapid uptake
of, IO drugs during the forecast period, some KOLs have mixed views on PD-1
checkpoint inhibitor use in NSCLC. They view the low response rates seen with
PD- 1/PD-L1 inhibitor therapy and the high costs of these drugs as negatives,
and speculate that their widespread use in all patients would be financially
impractical. GlobalData expects that these concerns will need to be addressed
in the form of combination therapies that increase response rates and
potentially elicit responses in PD-L1-negative patients; with regard to cost,
concerns can be addressed through pricing negotiations between companies and
national healthcare agencies in order to support the widespread use of IO drugs
in NSCLC. Alternatively, IO drugs may eventually be restricted to patients with
the highest expression levels of tumor PD-L1 as a way for payers and nationalized
healthcare systems to control costs in the long run.
this issue and all back issues online, please visit www.drug-dev.com.
Xuan is an Oncology Analyst at GlobalData in Boston. She provides
in-depth scientific analysis of products within the oncology pharmaceutical
sector and constructs market forecast models based on business intelligence.
She has authored several expert insights that delve into market analysis of
innovative treatment strategies in oncology. She earned her BS and PhD in
Microbiology, Immunology, and Molecular Genetics, from the University of
California, Los Angeles (UCLA). Prior to joining GlobalData, she was a post-doctoral
fellow at the John Wayne Cancer Institute in Santa Monica, California.
Volkan Gunduz is an Oncology Analyst at GlobalData
in Boston. He offers in-depth market intelligence
and data interpretation within the oncology
pharmaceuticals sector. He earned his PhD in Genetics at
Tufts University, where he studied the role of Retinoblastoma
tumor suppressor protein in bone development and cancer. He
his BSc in Molecular
Biology and Genetics at Bilkent University, Turkey. Previous to joining
GlobalData, he worked at Children’s Hospital Boston and New York University as
a post-doctoral fellow working on projects that investigated the impact of dietary
restriction on lung tumorigenesis and the gene network that regulates muscle stem