FDA Grants Priority Review to Genentech’s Personalized Medicine Entrectinib

SOUTH SAN FRANCISCO, Calif.–(BUSINESS WIRE)–Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY),
today announced that the U.S. Food and Drug Administration (FDA) has
accepted the company’s New Drug Applications (NDAs) and granted
Priority Review for entrectinib for the treatment of adult and pediatric
patients with neurotrophic tropomyosin receptor kinase (NTRK)
fusion-positive, locally advanced or metastatic solid tumors who have
either progressed following prior therapies or as initial therapy when
there are no acceptable standard therapies, and for the treatment of
people with metastatic, ROS1-positive non-small cell lung cancer
(NSCLC). These NDAs are based on results from the integrated analysis of
the pivotal Phase II STARTRK-2, Phase I STARTRK-1 and Phase I
ALKA-372-001 trials, and data from the Phase I/Ib STARTRK-NG study. The
FDA is expected to make a decision on approval by August 18, 2019.

“Entrectinib represents a unique approach to cancer treatment that can
potentially target a range of hard-to-treat and rare NTRK
fusion-positive tumors regardless of their site of origin, as well as
treat ROS1-positive non-small cell lung cancer,” said Sandra Horning,
M.D., chief medical officer and head of Global Product Development. “By
combining comprehensive genomic profiling with actionable targeted
therapies, like entrectinib, we are advancing our personalized
healthcare goal to find the right treatment for each patient. We are
working closely with the FDA to make this potential new option available
as soon as possible.”

The FDA grants Priority Review to medicines determined to have the
potential to provide significant improvements in the treatment,
prevention or diagnosis of a serious disease. Entrectinib was also
granted Breakthrough Therapy Designation (BTD) by the FDA in May 2017
for the treatment of NTRK fusion-positive, locally advanced or
metastatic solid tumors in adult and pediatric patients who have either
progressed following prior therapies or have no acceptable standard
therapies. BTD is designed to expedite the development and review of
medicines intended to treat serious or life-threatening diseases and to
help ensure people have access to them through FDA approval as soon as
possible.

Genentech is leveraging its expertise in developing personalized
medicines and advanced diagnostics, in conjunction with Foundation
Medicine, to develop a companion diagnostic that will help identify
people with ROS1 and NTRK gene fusions.

About the integrated analysis

The integrated analysis included data from 53 people with
ROS1-activating gene fusions and 54 people with locally advanced or
metastatic NTRK fusion-positive solid tumors (10 tumor types, >19
histopathologies) from the Phase II STARTRK-2, Phase I STARTRK-1 and
Phase I ALKA-372-001 trials. In addition, data from the Phase I/Ib
STARTRK-NG study in pediatric patients were also included in the NDAs.
The studies enrolled people across 15 countries and more than 150
clinical trial sites. Tumor types evaluated in the studies to date
included breast, cholangiocarcinoma, colorectal, gynecological,
neuroendocrine, non-small cell lung, salivary gland, pancreatic, sarcoma
and thyroid cancers.

  • STARTRK-2 is a Phase II, global, multicenter, open-label basket
    study in people with solid tumors that harbor an NTRK1/2/3, ROS1 or
    ALK-positive gene fusion. The primary endpoint is objective response
    rate (ORR), and duration of response (DoR) is a secondary endpoint.
    Other secondary outcome measures include time to response, clinical
    benefit rate, intracranial tumor response, progression-free survival
    (PFS), central nervous system (CNS) PFS and overall survival (OS).
  • STARTRK-1 is a Phase I, multicenter, open-label dose escalation
    study of a daily continuous dosing schedule in people with solid
    tumors with NTRK1/2/3, ROS1 or ALK gene fusions in the U.S. and South
    Korea. The trial assessed the safety and tolerability of entrectinib
    via a standard dose escalation scheme and determined the recommended
    Phase II dose.
  • ALKA-372-001 is a Phase I, multicenter, open-label dose
    escalation study of an intermittent and continuous entrectinib dosing
    schedule in people with advanced or metastatic solid tumors with
    TRKA/B/C, ROS1 or ALK gene fusions in Italy.
  • STARTRK-NG is a Phase I/Ib dose escalation and expansion study
    evaluating the safety and efficacy of entrectinib in children and
    adolescent patients with no curative first-line treatment option,
    recurrent or refractory extracranial solid tumors or primary CNS
    tumors, with or without TRK, ROS1 or ALK fusions.

Results from the integrated analysis showed entrectinib shrank tumors
(ORR) in more than half (57.4 percent) of people with NTRK
fusion-positive solid tumors. Objective responses to entrectinib were
seen across 10 different solid tumor types (median DoR = 10.4 months),
including in people with and without CNS metastases at baseline. In
these studies, entrectinib shrank tumors that had spread to the brain in
more than half of people (intracranial response [IC ORR] = 54.5
percent), with more than a quarter of these people having a complete
response.

Entrectinib shrank tumors in 77.4 percent of people with locally
advanced or metastatic ROS1-positive NSCLC. In addition, entrectinib
demonstrated a durable response of more than two years (median DoR =
24.6 months). Importantly, entrectinib was shown to shrink intracranial
tumors in more than half of people with CNS metastases at baseline (IC
ORR = 55.0 percent).

The safety profile of entrectinib was consistent with that seen in
previous analyses. The most commonly reported adverse reactions included
fatigue, constipation, altered sense of taste (dysgeusia), swelling
(edema), dizziness, diarrhea, nausea, nervous system disorders
(dysesthesia), shortness of breath (dyspnea), pain, anemia, cognitive
disorders, weight increased, vomiting, cough, blood creatinine increase,
joint pain (arthralgia), fever (pyrexia), and muscle pain (myalgia).

About entrectinib

Entrectinib (RXDX-101) is an investigational, oral medicine in
development for the treatment of locally advanced or metastatic solid
tumors that harbor NTRK1/2/3 or ROS1 gene fusions. It is a selective
tyrosine kinase inhibitor designed to inhibit the kinase activity of the
TRK A/B/C and ROS1 proteins, whose activating fusions drive
proliferation in certain types of cancer. Entrectinib can block ROS1 and
NTRK kinase activity and may result in the death of cancer cells with
ROS1 or NTRK gene fusions. Entrectinib is being investigated across a
range of solid tumor types, including breast, cholangiocarcinoma,
colorectal, gynecological, neuroendocrine, non-small cell lung, salivary
gland, pancreatic, sarcoma and thyroid cancers.

About NTRK fusion-positive cancer

Neurotrophic tyrosine receptor kinase (NTRK) fusion-positive cancer
occurs when the NTRK1/2/3 genes fuse with other genes, resulting in
altered TRK proteins (TRKA/TRKB/TRKC) that can activate signaling
pathways involved in proliferation of certain types of cancer. NTRK gene
fusions are tumor-agnostic, meaning they are present in tumors
irrespective of site of origin. These fusions have been identified in a
broad range of solid tumor types, including breast, cholangiocarcinoma,
colorectal, gynecological, neuroendocrine, non-small cell lung, salivary
gland, pancreatic, sarcoma and thyroid cancers. There is a high unmet
medical need for treatments for people with life-threatening and
hard-to-treat NTRK fusion-positive tumors.

About lung cancer

According to the American Cancer Society, it is estimated that more than
228,000 Americans will be diagnosed with lung cancer in 2019, and NSCLC
accounts for 84 percent of all lung cancers. It is estimated that
approximately 60 percent of lung cancer diagnoses in the United States
are made when the disease is in the advanced stages. While the ROS1 gene
fusion can be found in any person with NSCLC, young never-smokers have
the highest incidence of ROS1-positive NSCLC.

About Genentech in lung cancer

Lung cancer is a major area of focus and investment for Genentech, and
we are committed to developing new approaches, medicines and tests that
can help people with this deadly disease. Our goal is to provide an
effective treatment option for every person diagnosed with lung cancer.
We currently have four approved medicines to treat certain kinds of lung
cancer and more than 10 medicines being developed to target the most
common genetic drivers of lung cancer or to boost the immune system to
combat the disease.

About Genentech

Founded more than 40 years ago, Genentech is a leading biotechnology
company that discovers, develops, manufactures and commercializes
medicines to treat patients with serious and life-threatening medical
conditions. The company, a member of the Roche Group, has headquarters
in South San Francisco, California. For additional information about the
company, please visit http://www.gene.com.

Contacts

Media Contact:
Meghan Cox (650) 467-6800

Advocacy Contact:
Stephanie Bryant (312) 505-9789

Investor Contacts:
Loren Kalm (650) 225-3217
Karl Mahler 011
41 61 687 8503

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