Janssen Submits MA Application to the European MedicinesAgency Seeking Approval of Erdafitinib for the Treatment of Patients with LocallyAdvanced or Metastatic Urothelial Cancer with Susceptible FGFR Alterations

September 8, 2023 – Clinical Trials, Drug Discovery – FGFR, Janssen, Johnson & Johnson, urothelial cancer

Pending approval, erdafitinib, an investigational, once-daily oral pan-fibroblast growth factor
receptor (FGFR) tyrosine kinase inhibitor, will become the first therapy targeting FGFR
alterations in patients with metastatic urothelial carcinoma, one of Europe’s most common
. The submission is based on results from the phase 3 THOR study, which were featured in a
Late-Breaking Presentation Session at the 2023 ASCO Annual Meeting in June

8 September 2023 — Beerse, Belgium — The Janssen Pharmaceutical Companies of
Johnson & Johnson announced today the submission of a Marketing Authorisation (MA)
Application to the European Medicines Agency (EMA) seeking approval of erdafitinib
for the treatment of adult patients with locally advanced unresectable or metastatic
urothelial carcinoma (UC), harbouring susceptible fibroblast growth factor receptor 3
(FGFR3) genetic alterations, with disease progression during or following at least one line of
therapy containing a programmed death receptor-1 (PD-1) or programmed death-ligand 1
(PD-[L]1) inhibitor.

Europe has one of the highest rates of bladder cancer in the world, with more than 203,000
patients diagnosed in 2020 alone. UC is the most common form, and up to 20 percent of
patients with metastatic UC (mUC) have FGFR alterations. Patients with mUC, including
FGFR-driven tumours, face a particularly poor prognosis and the need for innovative
therapies remains high. Only 8% of people diagnosed at a late, metastatic stage
will survive for five years or more.

“For patients with advanced UC, including FGFR-driven tumours, outcomes remain poor and
treatment options are limited; therefore, there is a need for novel, targeted therapies,” said
Martin Vogel, EMEA Therapeutic Area lead Oncology at Janssen-Cilag GmbH. “We are excited
by the prospect of bringing innovative, personalised approaches to market for patients as
we work towards our wider goal of making this complex disease a more manageable and
ultimately curable condition.”

This MA application is supported by data from Cohort 1 of the randomised, controlled, open-label,
multicentre phase 3 THOR study (NCT03390504), evaluating the efficacy and safety of
erdafitinib versus chemotherapy. The study met its primary endpoint of overall survival
(OS), with patients who received erdafitinib achieving a median OS of over one year at the
prespecified interim analysis data cutoff. As the interim results met the predefined criteria
for superiority of treatment with erdafitinib over chemotherapy, the independent data safety
monitoring committee recommended that the study be stopped and that patients
randomised to chemotherapy be offered the opportunity to cross-over to erdafitinib. The
safety profile of erdafitinib observed in THOR was consistent with the previously reported
safety profile of erdafitinib in metastatic urothelial carcinoma (mUC). This pivotal data
from THOR were featured in a Late-Breaking Presentation Session (Abstract #LBA4619) at
the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting.

“This submission, and Janssen’s ongoing study of erdafitinib, reinforces our commitment to
deliver much-needed targeted therapies in the areas of high unmet need, including for
devastating diseases like metastatic UC,” said Kiran Patel MD, vice president of Clinical
Development, Solid Tumors at Janssen Research & Development. “Erdafitinib has
demonstrated promising results in advanced, FGFR-altered UC, making this submission a
vital step towards improving outcomes for patients in the future. The OS benefit we’ve seen
with erdafitinib also supports the need for biomarker testing for FGFR alterations in all
patients with metastatic UC.”

In April 2019, erdafitinib received accelerated approval from the U.S. Food and Drug
Administration (FDA) as a targeted therapy for adult patients with locally advanced or mUC
with susceptible FGFR3 or FGFR2 genetic alterations and who have progressed during or
following at least one line of prior platinum-containing chemotherapy, including within 12
months of neoadjuvant or adjuvant platinum-containing chemotherapy.10 On August 29,
Janssen submitted a supplemental New Drug Application (sNDA) to the U.S. FDA seeking
full approval of erdafitinib in this indication based on Cohort 1 of the Phase 3 THOR study.

About THOR
THOR (NCT03390504) is a phase 3 randomised, open-label, multicentre study evaluating
the efficacy and safety of erdafitinib. All patients included in the study had metastatic or
unresectable UC, with selected FGFR genetic alterations, and showed disease progression
during or after one or two prior lines of treatment. The study compared erdafitinib in two
cohorts; erdafitinib versus standard of care chemotherapy (investigators choice of docetaxel
or vinflunine) after at least one line of treatment including an anti-PD-(L)1 agent (Cohort
1); and erdafitinib compared to pembrolizumab after one prior treatment not containing an
anti-PD-(L)1 agent (Cohort 2). The trial consists of a screening step, a treatment phase
(from randomisation until disease progression, intolerable toxicity, withdrawal of consent or
decision by investigator to discontinue treatment) and a post-treatment follow-up (from
end-of-treatment to participant’s death, withdraws consent, lost to follow-up study
completion for the respective cohort, whichever comes first). A long-term extension period
is planned for after the clinical cut-off date is achieved for the final analysis of each cohort
and eligible patients will continue to benefit from the study intervention. The primary
endpoint of the study is overall survival (OS); progression free survival (PFS), objective
response rate (ORR), duration of response (DOR), patient-reported outcomes, safety and
pharmacokinetics (PK) are secondary endpoints. Results from Cohort 1 were presented at the 2023 ASCO Annual Meeting earlier this year; findings from Cohort 2 will be presented at an upcoming medical meeting.

About Erdafitinib
Erdafitinib is a once-daily, oral pan-fibroblast growth factor receptor (FGFR) tyrosine kinase
inhibitor being evaluated by Janssen Research & Development in phase 2 and 3 clinical
trials in patients with advanced urothelial cancer. In addition to the phase 3 THOR study, erdafitinib is being studied in the phase 2 THOR-2/BLC2003 (NCT04172675) study examining erdafitinib versus investigator choice of intravesical chemotherapy in participants who received Bacillus Calmette-Guérin and recurred with high risk non-muscle-invasive bladder cancer; the phase 1b/2 NORSE (NCT03473743) study of erdafitinib in combination with cetrelimab in patients with locally advanced or mUC and FGFR3 or FGFR2 gene alterations; the phase 2 RAGNAR (NCT04083976) study evaluating the safety and efficacy of erdafitinib in patients with advanced solid tumours, regardless of cancer type or tumour location (tumour-agnostic), driven by FGFR1–4 alterations; the phase 1 study (NCT05316155) investigating erdafitinib in patients with non-muscle invasive or muscle invasive bladder cancer with selected FGFR
alterations, given via the TARIS intravesical drug delivery system (TAR-210), which is designed to release erdafitinib in the bladder to treat localised bladder cancer, while potentially reducing systemic toxicities.
In 2008, Janssen Pharmaceutica NV entered into an exclusive worldwide license and collaboration agreement with Astex Pharmaceuticals to develop and commercialise erdafitinib.

About Urothelial Carcinoma
Urothelial carcinoma (UC), also known as transitional cell carcinoma, starts in the innermost lining of the bladder. Almost all bladder cancers – more than 90% – are UCs. Up to one in five patients (20%) diagnosed with mUC have a fibroblast growth factor receptor (FGFR) genetic alteration. FGFRs are a family of receptor tyrosine kinases that can be activated by genetic alterations in a variety of tumour types, and these alterations may lead to increased tumour cell growth and survival. FGFRs play a key role in several biological processes including tissue repair, inflammatory response and metabolism.
Fusions or mutations in the genes that control FGFR (known as FGFR1–4 alterations) may lead to the development and progression of certain cancers by increasing tumour cell growth and survival. Patients with advanced UC, including FGFR-driven tumours, face a poor prognosis and the need for innovative therapies remains high. The five-year survival rate for patients with metastatic bladder cancer that has spread to distant parts of the body is currently 8%.

About the Janssen Pharmaceutical Companies of Johnson & Johnson
At Janssen, we’re creating a future where disease is a thing of the past. We’re the
Pharmaceutical Companies of Johnson & Johnson, working tirelessly to make that future a
reality for patients everywhere by fighting sickness with science, improving access with
ingenuity and healing hopelessness with heart. We focus on areas of medicine where we
can make the biggest difference: Cardiovascular, Metabolism & Retina; Immunology;
Infectious Diseases & Vaccines; Neuroscience; Oncology; and Pulmonary Hypertension.
Learn more at www.janssen.com/emea.