08 GILEAD SCIENCES
direct acting antivirals continue to represent an unmet medical
need. Study results demonstrate that combining three potent
antivirals with different mechanisms of action and high barriers
to resistance can provide high cure rates for patients who have
failed other highly effective oral DAA regimens.
Gilead’s pending SOF/VEL/VOX fixed-dose combination was
granted Breakthrough Therapy designation by the U.S. FDA for
the treatment of chronic genotype 1 HCV patients who previously failed an NS5A inhibitor-containing regimen.
Additionally, the European Commission approved Gilead’s
Vemlidy (Tenofovir Alafenamide, TAF) for the treatment of Chronic Hepatitis B Virus Infection, which is the first new treatment for
chronic hepatitis B to be approved in Europe in nearly a decade.
TAF is a targeted prodrug of tenofovir that has demonstrated antiviral efficacy similar to Viread, but at one-tenth the dose. TAF is
associated with improved renal and bone lab safety parameters
compared to TDF in clinical trials.
Vemlidy was approved by the FDA in November 2016 for the
treatment of chronic HBV infection in adults with compensated
liver disease, and by the Japanese Ministry of Health, Labour and
Welfare in December 2016 for the suppression of viral replication
in chronic hepatitis B patients with evidence of hepatitis B virus
replication and abnormal liver function.
In the near term, Gilead has decent growth potential. Within
the next few years. Bictegravir could significantly boost HIV franchise sales. Bictegravir is a combo alternative integrase inhibitor
that would come in single tablet form. GSK’s Tivicay has led the
market in this space with its HIV segment up 57% in the first
quarter, led by Tivicay sales. Gilead stands to recoup some of the
market share it lost in this space once Bictegravir hits the market.
Recent trials demonstrated that Gilead’s bictegravir combination could offer an improvement over existing therapies. In four
Phase III studies, bictegravir met its primary objective of non-inferiority. Gilead plans to submit a marketing authorization application for BIC/FTC/TAF in the EU in the third quarter of 2017.
Three of the ongoing studies are designed to explore the safety and efficacy of BIC/FTC/TAF compared to triple-therapy regimens containing dolutegravir in treatment-naïve patients and
virologically suppressed patients switching from an existing antiretroviral regimen with dolutegravir. A fourth study in virologically suppressed patients compares switching to BIC/FTC/TAF
versus remaining on a suppressive regimen of two nucleoside/
nucleotide reverse transcriptase inhibitors and protease inhibitor.
Because people with HIV are living longer and are increasingly likely to be taking medication for other conditions, such as
heart and liver disease, they are exposed for longer periods of
time to the virus and to the medications used to treat it. Therefore, new, effective treatment options are needed that are also
tolerable, and offer convenient dosing.
Helping to fulfill this need, Gilead’s once-daily single tablet
regimen Odefsey for the treatment of HIV-1 in certain patients,
was granted approval in the EU in June 2016, and in the U.S.
in March 2016. Odefsey combines Gilead’s emtricitabine and
tenofovir alafenamide (marketed as Descovy) with rilpivirine,
marketed by Janssen Sciences Ireland UC, a Johnson & Johnson
company. Following the approval of Genvoya in November 2015,
Odefsey is Gilead’s second STR based on the Descovy backbone
to receive marketing authorization in the EU and is currently the
smallest pill of any STR for the treatment of HIV.
Additionally, the European Commission approved Gilead’s
once-daily Truvada for reducing the risk of sexually acquired HIV-
1. This represents the first antiretroviral medicine to be licensed in
Europe for pre-exposure prevention, in combination with safer-sex practices, to reduce the risk of HIV-1 in high risk adults.
To maintain its position in the top 10, Gilead needs a new
outlet. So far, its oncology efforts have been challenged. Its only
approved oncology asset is idelalisib, marketed as Zydelig, which
is a second line therapy with boxed warning in three indications:
Relapsed chronic lymphocytic leukemia (CLL), in combination
with rituximab, in patients for whom rituximab alone would be
considered appropriate therapy due to other co-morbidities; Relapsed follicular B-cell non-Hodgkin lymphoma in patients who
have received at least two prior therapies; and Relapsed small
lymphocytic lymphoma (SLL) in patients who have received at
least two prior therapies. Needless to say, Zydelig hasn’t taken off
in the oncology sector as anticipated.
Other oncology pipeline assets include: Andecaliximab, an
MMP9 inhibitor currently in Phase III trials in gastric cancer, entospletinib, a SYK inhibitor in Phase II in acute myeloid leukemia,
and hematopoietic and lymphoid malignancies; and tirabrutinib,
a BTK inhibitor in Phase II for B-cell malignancies, as well as
couple candidates in early development.
In November, Gilead achieved top-line results from two
Phase III trials (SIMPLIFY 1 and 2) that evaluated momelotinib,
an investigational inhibitor of Janus kinase (JAK) compared to
ruxolitinib or best alternative therapy (BAT) in myelofibrosis,
a relatively rare bone marrow cancer. The SIMPLIFY-1 study
achieved its pre-specified primary endpoint of non-inferiority to
ruxolitinib for splenic response rate, defined as the percentage
of patients experiencing a 35% reduction in spleen volume, but
SIMPLIFY-2 failed to achieve its primary endpoint of superiority
of momelotinib compared to BAT in patients previously treated
In the “other” category, NASH, or nonalcoholic steatohepatitis, is a therapeutic area being pursued by Gilead, and several
other drug developers. Allied Market Research estimates that
the global market is expected to reach $1.6 billion by 2020. The
high prevalence of Type II diabetes and obesity, which leads to
NASH and other nonalcoholic fatty liver diseases, has created
this market. North America has the highest rates of NASH and
other nonalcoholic fatty liver diseases and Europe ranks second
in terms of the prevalence.
Results from a Phase II trial evaluating the investigational
apoptosis signal-regulating kinase 1 (ASK1) inhibitor selonsertib
alone or in combination with the monoclonal antibody simtu-zumab (SIM) in NASH and moderate to severe liver fibrosis,
demonstrated regression in fibrosis that was, in parallel, associated with reductions in other measures of liver injury in patients
treated with selonsertib.
While competition for Gilead’s top franchises took its toll in
2016, HCV and HIV assets moving through the pipeline are likely
to put this antiviral authority back on top—remaining there may
prove more difficult. A breakthrough product in oncology, cell
therapy, or NASH is needed in the long term. CP