Gilead Sciences, Inc. (Nasdaq: GILD) today announced results of a Phase
2 study (Study 101-09) evaluating idelalisib, an investigational oral
inhibitor of PI3K delta, for the treatment of patients with indolent
non-Hodgkin’s lymphoma (iNHL) that is refractory (non-responsive) to
rituximab and to alkylating-agent-containing chemotherapy. In this
study, single-agent treatment with idelalisib achieved an overall
response rate of 57 percent with a median duration of response of 12.5
months. The data were presented today during an oral session at the
Annual Meeting of the American Society of Hematology (ASH) in New
Orleans (Abstract #85).
“It has been more than ten years since a treatment with a novel
mechanism of action has been approved for indolent NHL, underscoring the
medical need for new treatments for patients who are no longer
responsive to currently available therapies,” said Ajay Gopal, MD,
Associate Professor, University of Washington School of Medicine and
Associate Member, Clinical Research Division, Fred Hutchinson Cancer
Research Center in Seattle, Washington. “The overall response rate and
durability of response observed in this study suggest that idelalisib
may become a valuable new therapy for iNHL patients who have very
limited treatment options.”
Of the 71 patients who responded to therapy, seven (six percent)
achieved a complete response, 63 (50 percent) had a partial response and
one (one percent) had a minor response. Among patients who responded,
the median duration of response was 12.5 months and the median time to
response was 1.9 months. Median progression-free survival for all
patients was 11.0 months and median overall survival was 20.3 months.
Ninety percent of patients experienced shrinkage in lymph node size.
The most common Grade ≥3 adverse event was diarrhea, which was reported
in 16 patients (13 percent). Grade ≥3 transaminase elevations (a measure
of liver function) were reported in 16 patients (13 percent). Of the 16
patients who had Grade ≥3 transaminase elevations, 14 were retreated
with idelalisib and of those, 10 (71 percent) had no recurrence. Grade
≥3 neutropenia occurred in 34 patients (27 percent). Twenty-five
patients (20 percent) discontinued therapy because of adverse events.
These results in iNHL support Gilead’s recent regulatory filings for
idelalisib in the United States and European Union. On September 11,
2013, Gilead submitted a New Drug Application to the U.S. Food and Drug
Administration for idelalisib for the treatment of refractory iNHL.
Following Gilead’s NDA submission for iNHL, FDA granted idelalisib a
Breakthrough Therapy designation for chronic lymphocytic leukemia (CLL)
in relapsed patients. Gilead is now engaging in a dialogue with the FDA
regarding a regulatory filing in CLL.
Gilead’s Marketing Authorization Application (MAA) for idelalisib for
the treatment of iNHL and CLL was validated by the European Medicines
Agency (EMA) on November 20. Review of the MAA will be conducted under
the centralized licensing procedure, which, when finalized, provides one
marketing authorization in all 28 member states of the European Union
(EU). The Committee for Medicinal Products for Human Use (CHMP) has
accepted Gilead’s request for accelerated assessment for idelalisib, a
designation that is granted to new medicines of major public health
interest. Although accelerated assessment could shorten the review time
of idelalisib by approximately two months, it does not guarantee a
positive opinion from the CHMP or final approval by the European
Commission. If approved, idelalisib could be available for marketing in
the EU in the second half of 2014.
About Study 101-09
Study 101-09 is a Phase 2, open-label, single-arm efficacy and safety
study of idelalisib in patients with previously treated iNHL that is
refractory both to rituximab and to alkylating-agent-containing
chemotherapy (refractory defined as no response while on therapy or
progression within six months of completion of therapy).
The study enrolled 125 patients from approximately 50 study sites in the
United States and Europe. Patients were a median age of 64 and had
confirmed diagnoses of follicular lymphoma (n=72), small lymphocytic
lymphoma (n=28), lymphoplasmacytic lymphoma / Waldenström
macroglobulinemia (n=10) or marginal zone lymphoma (n=15). Patients had
received a median of four prior treatment regimens before study entry,
with 79 percent of patients refractory to two or more prior regimens and
90 percent refractory to their most recent regimen. All patients
received idelalisib 150 mg twice daily and are allowed to continue daily
dosing as long as they benefit from therapy. The primary endpoint of the
study is overall response rate, defined as the proportion of patients
achieving a confirmed complete or partial response with idelalisib
treatment (response definitions based on standard criteria; responses
assessed by study investigators and an independent review committee).
About Idelalisib
Idelalisib is an investigational, highly selective oral inhibitor of
phosphoinositide 3-kinase (PI3K) delta. PI3K delta signaling is critical
for the activation, proliferation, survival and trafficking of B
lymphocytes and is hyperactive in many B-cell malignancies. Idelalisib
is being developed both as a single agent and in combination with
approved and investigational therapies.
Gilead’s clinical development program for idelalisib in iNHL includes
Study 101-09 in highly refractory patients and two Phase 3 studies of
idelalisib in previously treated patients. In addition to Study 116, the
development program in CLL includes two ongoing Phase 3 studies of
idelalisib in previously treated patients. Combination therapy with
idelalisib and GS-9973, Gilead’s novel spleen tyrosine kinase (Syk)
inhibitor, also is being evaluated in a Phase 2 trial of patients with
relapsed or refractory CLL, iNHL and other lymphoid malignancies.
Additional information about clinical studies of idelalisib and Gilead’s
other investigational cancer agents can be found at www.clinicaltrials.gov.
Idelalisib and GS-9973 are investigational products and their safety and
efficacy have not been established.
About Indolent Non-Hodgkin’s Lymphoma
Indolent non-Hodgkin’s lymphoma refers to a group of largely incurable
slow-growing lymphomas that run a relapsing course after therapy and can
lead ultimately to life-threatening complications such as serious
infections and marrow failure. Most iNHL patients are diagnosed at an
advanced stage of disease, and median survival from time of initial
diagnosis for patients with the most common form of iNHL, follicular
lymphoma, is 8 to 10 years. The outlook for refractory iNHL patients is
significantly poorer.
About Gilead Sciences
Gilead Sciences is a biopharmaceutical company that discovers, develops
and commercializes innovative therapeutics in areas of unmet medical
need. The company’s mission is to advance the care of patients suffering
from life-threatening diseases worldwide. Headquartered in Foster City,
California, Gilead has operations in North and South America, Europe and
Asia Pacific.
Forward-Looking Statement
This press release includes forward-looking statements within the
meaning of the Private Securities Litigation Reform Act of 1995 that are
subject to risks, uncertainties and other factors, including the
possibility of unfavorable results from clinical trials involving
idelalisib, including in combination with GS-9973 or other product
candidates. Gilead also faces risks related to its ability to file for
U.S. regulatory approval of idelalisib for CLL in the currently
anticipated timelines. Gilead may also be unable to enroll patients in
Phase 3 studies and may need to modify or delay these studies. In
addition, FDA, EMA and other regulatory agencies may not approve
idelalisib for the treatment of iNHL or CLL in the anticipated timelines
or at all, and any marketing approval may have significant limitations
on its use. As a result, idelalisib may never be successfully
commercialized. Further, Gilead may make a strategic decision to
discontinue development of idelalisib, as a single agent or in
combination with other products if, for example, Gilead believes
commercialization will be difficult relative to other opportunities in
its pipeline. These risks, uncertainties and other factors could cause
actual results to differ materially from those referred to in the
forward-looking statements. The reader is cautioned not to rely on these
forward-looking statements. These and other risks are described in
detail in Gilead’s Quarterly Report on Form 10-Q for the quarter
ended September 30, 2013, as filed with the U.S. Securities and Exchange
Commission. All forward-looking statements are based on information
currently available to Gilead, and Gilead assumes no obligation to
update any such forward-looking statements.
For more information on Gilead Sciences, please visit the company’s
website at www.gilead.com,
follow Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs
at 1-800-GILEAD-5 or 1-650-574-3000.
Copyright Business Wire 2013