FDA Grants Breakthrough Therapy Designation for Genentech’s Alecensa®

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced today that it has received a second Breakthrough Therapy Designation (BTD) from the U.S. Food and Drug Administration (FDA) for its anaplastic lymphoma kinase (ALK) inhibitor, Alecensa (alectinib). The latest BTD was granted for the treatment of adult patients with advanced ALK-positive non-small cell lung cancer (NSCLC) who have not received prior treatment with an ALK inhibitor.
“The J-ALEX study that supports the second Breakthrough Designation for
Alecensa showed superior efficacy versus the standard of care,
crizotinib, in Japanese people with advanced ALK-positive disease,” said
Sandra Horning, M.D., chief medical officer and head of Global Product
Development. “The decision by the FDA to grant a second Breakthrough
Therapy Designation is recognition of the clinically meaningful
improvement in efficacy and safety that Alecensa brings to the care of
people with advanced ALK-positive lung cancer who have not received
prior treatment with an ALK inhibitor.”
The FDA’s Breakthrough Therapy Designation is designed to expedite the
development and review of medicines intended to treat serious diseases
and to help ensure patients have access to them through FDA approval as
soon as possible. Alecensa received its first FDA BTD in June 2013 for
people with ALK-positive NSCLC whose disease progressed on treatment
with crizotinib.
Alecensa was granted accelerated approval by the FDA in December 2015
for the treatment of people with ALK-positive NSCLC who have progressed
on or are intolerant to crizotinib. ALEX, a global, randomized Phase III
study, is ongoing, comparing Alecensa to crizotinib as an initial
(first-line) treatment for people with advanced NSCLC whose tumors were
characterized as ALK-positive by a companion VENTANA ALK (D5F3) CDx
Assay immunohistochemistry (IHC) test developed by Roche Tissue
Diagnostics. This study is part of the company’s commitment to convert
the current accelerated approval in people with ALK-positive, metastatic
NSCLC who have progressed on or are intolerant to crizotinib to a full
approval as an initial treatment.
About J-ALEX
The J-ALEX study conducted by Chugai is an open-label, randomized Phase
III study that compared the efficacy and safety of Alecensa to
crizotinib in Japanese people. The J-ALEX study enrolled 207 people with
ALK-positive, advanced or recurrent NSCLC who had not been previously
treated with an ALK inhibitor. People were randomized to the Alecensa
group or the crizotinib group in a one-to-one ratio. Results include:

• Alecensa reduced the risk of disease worsening or death (progression
  free survival, PFS) by 66 percent compared to crizotinib (HR=0.34, 99
  percent CI: 0.17-0.70, p<0.0001).
• Median PFS was not reached in the Alecensa arm (95 percent CI: 20.3
  months-not estimated) versus 10.2 months in the crizotinib arm (95
  percent CI: 8.2-12.0).

• Grade 3-4 adverse events (AEs) occurred with greater frequency in the
  crizotinib arm compared to the Alecensa arm (27 percent vs. 51
  percent).
• The most common AE occurring with > 30 percent frequency with Alecensa
  was constipation (36 percent). The most common AEs for crizotinib were
  nausea (74 percent), diarrhea (73 percent), vomiting (59 percent),
  visual disturbance (55 percent), alteration in taste (dysgeusia; 52
  percent), constipation (46 percent), and an elevation in liver enzymes
  called alanine transaminase (ALT, 32 percent) and aspartate
  transaminase (AST, 31 percent).

About Lung Cancer
According to the American Cancer Society, it is estimated that more than
224,000 Americans will be diagnosed with lung cancer in 2016, and NSCLC
accounts for 85 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.
About Alecensa
Alecensa is a kinase inhibitor approved for the treatment of people with
anaplastic lymphoma kinase (ALK)-positive, metastatic non-small cell
lung cancer (NSCLC) who have progressed on or are intolerant to
crizotinib.
This indication is approved under accelerated approval based on tumor
response rate and duration of response (DOR). Continued approval for
this indication may be contingent upon verification and description of
clinical benefit in confirmatory trials.
Important Safety Information
Everyone reacts differently to treatment with Alecensa. It’s important
to know the most serious and most common side effects with Alecensa.
A doctor may lower the dose or stop treatment with Alecensa if any
serious side effects occur. Patients taking Alecensa should contact
their doctor right away if they have any of the following side effects.
Alecensa may cause serious side effects, including:
Liver problems (hepatotoxicity). Alecensa may cause liver injury.
A doctor will do blood tests at least every 2 weeks for the first 2
months and as needed during treatment with Alecensa. Patients taking
Alecensa should tell their doctor right away if they experience any of
the following signs and symptoms:

• Feeling tired
• Feeling less hungry than usual
• Yellowing of the skin or whites of the eyes
• Dark urine
• Itchy skin
• Nausea or vomiting
• Pain on the right side of stomach area
• Bleeding or bruising more easily than normal

Lung problems. Alecensa may cause severe or life-threatening
swelling (inflammation) of the lungs during treatment.
Symptoms may be similar to those symptoms from lung cancer. Patients
taking Alecensa should tell their doctor right away if they have any new
or worsening symptoms, including:

• Trouble breathing
• Shortness of breath
• Fever
• Cough

Slow heartbeat (bradycardia). Alecensa may cause very slow
heartbeats that can be severe. A doctor will check a patient’s heart
rate and blood pressure during treatment with Alecensa. Patients taking
Alecensa should tell their doctor right away if they feel dizzy,
lightheaded, or faint during treatment with Alecensa. Patients taking
Alecensa should tell their doctor if they take any heart or blood
pressure medicines.
Muscle pain, tenderness, and weakness (myalgia). Muscle problems
are common with Alecensa and can be severe. A doctor will do blood tests
at least every 2 weeks for the first month and as needed during
treatment with Alecensa. Patients taking Alecensa should tell their
doctor right away if they have any new or worsening signs and symptoms
of muscle problems, including unexplained muscle pain or muscle pain
that does not go away, tenderness, or weakness.
Before taking Alecensa, patients should tell their doctor about all
medical conditions, including if they:

• Have liver problems
• Have lung or breathing problems
• Have a slow heartbeat

• Are pregnant or plan to become pregnant. Alecensa can harm an unborn
  baby. Patients taking Alecensa should tell their doctor right away if
  they become pregnant during treatment with Alecensa or think they may
  be pregnant
  • Women who are able to become pregnant should use effective
    birth control during treatment with Alecensa and for one week
    after the final dose of Alecensa
  • Men who have female partners that are able to become
    pregnant should use effective birth control during treatment with
    Alecensa and for three months after the final dose of Alecensa
• Are breastfeeding or plan to breastfeed. It is not known if Alecensa
  passes into breast milk. A patient should not breastfeed during
  treatment with Alecensa and for one week after the final dose of
  Alecensa. Patients should talk with their doctor about the best way to
  feed their baby during this time.

Patients taking Alecensa should tell their doctor about all the
medicines they take, including prescription medicines,
over-the-counter medicines, vitamins, and herbal supplements.
Patients taking Alecensa should avoid spending time in the sunlight
during treatment with Alecensa and for seven days after the final dose
of Alecensa. Patients taking Alecensa may burn more easily and get
severe sunburns. Patients taking Alecensa should use sunscreen and lip
balm with a SPF 50 or greater to help protect against sunburn.
The most common side effects of Alecensa include:

• Tiredness
• Constipation
• Swelling in hands, feet, ankles, and eyelids

These are not all of the possible side effects of Alecensa. For more
information, patients should ask their doctor or pharmacist. Patients
should call their doctor for medical advice about side effects.
Report side effects to the FDA at (800) FDA-1088 or https://www.fda.gov/medwatch.
Patients and caregivers may also report side effects to Genentech at
(888) 835-2555.
Please see additional Important Safety Information in full Prescribing
Information, including Patient Information.
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 three 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 40 years ago, Genentech is a leading biotechnology company that
discovers, develops, manufactures and commercializes medicines to treat
patients with serious or 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 https://www.gene.com.