18 • MED AD NEWS FEBRUARY 2018
carcinoma that use the synNotch technology. The
company’s leading pre-clinical candidate targets
Kite entered into a clinical trial collaboration
with P;zer in January 2018. The companies are
exploring the safety and e;cacy of the combination of Yescarta and P;zer’s fully humanized
4-1BB agonist monoclonal antibody utomilumab
in patients with refractory large B-cell lymphoma.
A multi-center Phase 1/2 study sponsored by Kite
is scheduled to start in 2018. The results of this trial
will be used to assess options for further development of this combination or similar ones between
Kite’s engineered T cell products and utomilumab.
Also known as PF-05082566, utomilumab is
an investigational 4-1BB agonist that has been
demonstrated in preclinical models to enhance T
cell mediated immune responses. P;zer is studying utomilumab in hematologic cancers and solid
tumors as a single agent and in combination with
other anti-cancer therapies. Evidence suggests
that 4-1BB, a costimulatory protein expressed on
activated T cells, is upregulated upon exposure to
CD19-expressing tumor cells. Utomilumab has the
potential to enhance T cell proliferation and activity by augmenting the CD28 costimulatory domain of Yescarta with exogenous 4-1BB signaling.
Gilead’s product pipeline included a potentially
huge growth driver before the company acquired
Kite and Yescarta, known as BIC/FTC/TAF. The
;xed-dose combination is composed of bicte-gravir (50 mg) (BIC), an integrase strand transfer
inhibitor, and emtricitabine/tenofovir alafenamide
(200/25 mg) (FTC/TAF), a dual-NRTI backbone, for
treating HIV-1 infection.
During third-quarter 2017, Gilead announced
that the U.S. FDA granted priority review for a new
drug application for BIC/FTC/TAF. The company
submitted the NDA with a priority review voucher
on June 12, 2017, and U.S. regulators set a target
action date under the Prescription Drug User Fee
Act of Feb. 12, 2018. On Feb. 7, as this magazine
went to press, the product captured FDA approval
under the trade name Biktarvy.
Also during the 2017 third quarter, Gilead reported detailed 48-week results from two Phase
3 studies investigating the e;cacy and safety
of Biktarvy for treating HIV-1 infection in treatment-naïve adults. In the clinical trials, BIC/FTC/
TAF was found to be statistically non-inferior to
regimens containing dolutegravir (50 mg). Also,
Gilead’s marketing authorization application for
BIC/FTC/TAF has been fully validated and is under
review by the European Medicines Agency.
“Bictegravir/F/TAF is expected to become Gil-
ead ’s biggest growth driver, with forecast sales
of $5.1bn in 2022,” according to EvaluatePharma
sellside consensus. “The project could be the top
launch of this year (2018).”
The European Commission and FDA during
July approved Vosevi as a once-daily single-tablet
regimen for treating HCV infection in adults with
genotypes 1-6. Vosevi is the ;rst single-tablet reg-
imen for patients who have previously failed ther-
apy with direct-acting antiviral (DAA) treatments
and is the newest regimen in Gilead’s portfolio of
sofosbuvir-based HCV DAA treatments.
Appearing for the ;rst time in this annual report, Incyte’s dedicated researchers are focused on transforming the treatment
of cancer and the company’s product portfolio is
expanding. Incyte’s drug discovery e;orts were
founded during 2002 by a team of world-class
scientists striving to create innovative medicines.
According to management, the rigorous pursuit
of scienti;c excellence remains at the core of the
Wilmington, Del.-based biopharmaceutical company today.
Incyte’s debut on this yearly list is due in no small
part to the exciting market potential of the anticipated blockbuster melanoma medicine epacadostat (product code INCB024360). The immunosup-pressive e;ects of indoleamine 2,3-dioxygenase 1
(IDO1) enzyme activity on the tumor microenvironment aid cancer cells in evading immunosur-veillance. Epacadostat is an investigational, highly
potent and selective oral inhibitor of the enzyme
IDO1. In single-arm studies, the combination of
epacadostat and immune checkpoint inhibitors
has demonstrated proof-of-concept in patients
with unresectable or metastatic melanoma, non-small cell lung cancer, renal cell carcinoma, squamous cell carcinoma of the head and neck and
bladder cancer. In these studies, epacadostat in
combination with the CTLA- 4 inhibitor ipilimum-ab or the PD-1 inhibitors Keytruda or nivolumab
improved response rates versus studies of the immune checkpoint inhibitors on their own.
“Incyte is leading the IDO inhibition ;eld, and
is due to release the ;rst rigorous phase III data
in this space in the ;rst half of 2018,” according to
EvaluatePharma analysis. “Echo-301 tests a com-
bination of epacadostat with Merck’s Keytruda in
;rst-line melanoma, a tumor type that has already
been transformed by the arrival of the anti-PD-1
The ECHO clinical study program was estab-
lished to investigate the e;cacy and safety of
epacadostat as a core component of combo
therapy in oncology. Phase 1 and Phase 2 trials
are assessing epacadostat in combination with
PD-1 and PD-L1 inhibitors in a wide range of solid
tumor types as well as hematological malignan-
cies. ECHO-301 (NCT02752074) – a Phase 3 ran-
domized, double-blind, placebo-controlled trial
evaluating the blockbuster medication Keytruda
in combination with epacadostat or placebo for
treating patients with unresectable or metastatic
melanoma – is under way and fully recruited.
In collaboration with Merck and Bristol-Myers
Squibb, preparations for the next wave of eight
pivotal Phase 3 studies of epacadostat in combination with PD-1 antagonists continue as planned.
Initiation of these studies was expected before
Incyte got onto the marketing map via its ;rst
commercial product, Jaka; (ruxolitinib). Jaka; is
approved in the United States for patients with
intermediate or high-risk myelo;brosis and for
patients with polycythemia vera (PV) who have
had an inadequate response to or are intolerant of
hydroxyurea. The ;rst-in-class JAK1/JAK2 inhibitor
is marketed by Incyte in the United States and by
Novartis as Jakavi outside the country.
Incyte continues to study and develop Jaka;
through a variety of clinical trials. In December 2017, Incyte announced new 208-week (4-
year) follow-up data from the ongoing, global,
multi-center, open-label Phase 3 RESPONSE trial
comparing the e;cacy and safety of Jaka; with
best available therapy in patients with PV who are
resistant to or intolerant of hydroxyurea (HU). The
pre-planned data analysis demonstrated a durable primary response to Jaka; in patients with PV
who are resistant to or intolerant of HU and the
overall safety pro;le remained consistent with previously reported 80-week RESPONSE data.
Incyte announced during November that the
;rst patient had been treated in the RESET pivotal
study investigating ruxolitinib versus anagrelide
for the treatment of essential thrombocythemia
patients who are resistant to or intolerant of HU.
The REACH1 pivotal study exploring ruxolitinib
in patients with steroid-refractory acute graft-versus-host disease (GVHD) is on track to deliver
results in ;rst-half 2018. If successful, Incyte anticipates ;ling an sNDA seeking accelerated approval
of ruxolitinib in this indication in 2018. Three additional pivotal studies are investigating the role of
JAK inhibition in GVHD (REACH2 and REACH3 with
ruxolitinib, and GRAVITAS-301 with itacitinib).
Baricitinib is on track to become in the near
term Incyte’s second commercial product in the
United States. The once-daily oral JAK inhibitor is
undergoing clinical trials for in;ammatory and autoimmune diseases.
Eli Lilly and Incyte agreed during December
2009 on an exclusive worldwide license and col-
laboration agreement for the development and
commercialization of baricitinib and certain fol-
low-on compounds for patients with in;ammato-
ry and autoimmune diseases. Baricitinib was ;led
for regulatory review seeking marketing clearance
for treating rheumatoid arthritis in the United
States, the European Union and Japan in 2016. Ba-
ricitinib was approved in the EU during February
2017 and in Japan during July 2017. In April 2017,
the FDA issued a Complete Response Letter on the
NDA for baricitinib. Lilly intended to re;le the New
Drug Application with the U.S. regulatory agency
before the end of January 2018. The companies
anticipate that U.S. regulators will classify the ap-
plication as a Class II resubmission, which would
kick o; a new six-month review cycle. The drug
candidate remains under review in other markets.
Baricitinib is additionally being investigated for
the treatment of atopic dermatitis and systemic
lupus erythematosus. In September, Lilly and Incyte announced that baricitinib met the primary
endpoint in a Phase 2 trial in patients with moderate-to-severe atopic dermatitis. The Phase 3
program for psoriatic arthritis is expected to start
During November, Lilly and Incyte reported that
patients with moderate-to-severe rheumatoid
arthritis treated with baricitinib reported greater
improvements in pain control when compared to
Humira (adalimumab) or placebo. AbbVie’s Humira is the world’s best-selling Rx medicine.
Incyte and Syros Pharmaceuticals came to
terms in January 2018 on a target discovery, research collaboration and option agreement. Syros
will use its proprietary gene control platform to
identify novel therapeutic targets with a concentration in myeloproliferative neoplasms (MPNs),
and Incyte will receive options to obtain exclusive
global rights to intellectual property resulting from
the collaboration for up to seven validated targets.
Incyte will have exclusive global rights to develop
and commercialize any therapies through the collaboration that modulate those validated targets.
“Through this collaboration, we believe that Syros’ gene control platform will allow us to advance
our understanding of the underlying biology of
MPNs and potentially uncover new molecular targets for drug discovery,” noted Reid Huber, Ph.D.,
chief scienti;c o;cer of Incyte.
Incyte and AstraZeneca during October 2017
announced an expanded clinical study collaboration. The companies plan to initiate a Phase 3
study of epacadostat in combination with AstraZeneca’s PD-L1 antagonist Im;nzi (durvalumab)
in patients with Stage III non-small cell lung cancer
during ;rst-half 2018.
“ ... we seek to position IDO1 enzyme inhibition
as a key component of combination immunotherapy,” remarked Steven Stein, M.D., chief medical
o;cer at Incyte.