Genentech’s Gazyva (Obinutuzumab) Delivers Positive Topline Results for Phase II Lupus Nephritis Study

  • NOBILITY showed that Gazyva helped more patients achieve a complete
    renal response when added to standard of care
  • The Phase II study met both primary and key secondary endpoints
  • There are currently no FDA-approved therapies for lupus nephritis

SOUTH SAN FRANCISCO, Calif.–(BUSINESS WIRE)–Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY),
today announced positive topline results for NOBILITY, a Phase II
clinical trial investigating the safety and efficacy of Gazyva®
(obinutuzumab) for adults with proliferative lupus nephritis. The study
met its primary endpoint, showing Gazyva, in combination with standard
of care (mycophenolate mofetil or mycophenolic acid and
corticosteroids), demonstrated enhanced efficacy compared to placebo
plus standard of care alone in achieving complete renal response at one
year. In addition, Gazyva met key secondary endpoints showing improved
overall renal responses (complete and partial renal response) and
serologic markers of disease activity as compared to placebo.

“There are no FDA-approved treatments for lupus nephritis, a potentially
life-threatening condition in which patients are at high risk for
progressing to end-stage renal disease or death,” said Sandra Horning,
M.D., chief medical officer and head of Global Product Development. “We
have been investigating a possible treatment for lupus nephritis for
more than a decade and have integrated key learnings from that
experience in how we study the condition. We are encouraged by the
NOBILITY results, which showed a statistically significant difference in
achievement of complete renal response, overall renal response, and
other measures of disease activity and support the potential for a new
treatment option for people living with lupus nephritis.”

Lupus nephritis is a severe and potentially life-threatening
manifestation of systemic lupus erythematosus (SLE) resulting from
inflammation of the kidneys, with proliferative lupus nephritis being
the most severe form and associated with the highest risk of end-stage
renal disease and death.1,2 In addition to meeting the
primary endpoint, the study’s key secondary endpoint, defined as
achievement of overall renal response (complete or partial renal
response) at one year, was also met. No new safety signals were observed
with Gazyva in the study at the time of this analysis. The full results
from the study will be presented at a future medical meeting.

About the NOBILITY Study

The Phase II, randomized, double-blind, placebo-controlled, multi-center
study, NOBILITY (NCT02550652), compares the safety and efficacy of
Gazyva, combined with mycophenolate mofetil (MMF) or mycophenolic acid
(MPA) and corticosteroids, to placebo, combined with MMF or MPA and
corticosteroids, in adult patients with ISN/RPS 2003 Class III or IV
proliferative lupus nephritis. The study enrolled 126 people who were
randomized to receive Gazyva or placebo infusions on Days 1, 15, 168,
and 182. The primary endpoint was the proportion of participants who
achieved a protocol-defined complete renal response (CRR) at 52 weeks.

About Lupus Nephritis

Lupus nephritis is a severe and potentially life-threatening disorder of
the kidneys. Lupus nephritis is a complication of systemic lupus
erythematosus (SLE), an autoimmune disease where a person’s own immune
system attacks healthy cells and organs.1 An estimated 1.5
million Americans are affected by lupus, with approximately 70 percent
of cases representing SLE.1,3 Up to 60 percent of people with
SLE will develop lupus nephritis, and up to 25 percent of people with
the condition develop end-stage renal disease.1,2 Lupus
nephritis overwhelmingly impacts women, particularly young women of
color. About 90 percent of those diagnosed are women, and
African-American, Hispanic, Native American and Asian-American women are
two to three times more likely than Caucasian women to get lupus.3,4
Currently, there is no cure for lupus or lupus nephritis.4

About Gazyva

Gazyva is an engineered monoclonal antibody designed to attach to CD20,
a protein found only on certain types of B-cells. It is thought to work
by attacking targeted cells both directly and together with the body’s
immune system. In the United States, Gazyva is part of a collaboration
between Genentech and Biogen. Combination studies investigating Gazyva
with other approved or investigational medicines, including cancer
immunotherapies and small molecule inhibitors, are underway across a
range of blood cancers.

Gazyva Indications

Gazyva® (obinutuzumab) is a prescription medicine used:

  • With the chemotherapy drug, chlorambucil, to treat chronic lymphocytic
    leukemia (CLL) in adults who have not had previous CLL treatment.
  • With the chemotherapy drug, bendamustine, followed by Gazyva alone for
    follicular lymphoma (FL) in adults who did not respond to a
    rituximab-containing regimen, or whose FL returned after such
    treatment.
  • With chemotherapy, followed by Gazyva alone in those who responded, to
    treat stage II bulky, III, or IV FL in adults who have not had
    previous FL treatment.

Important Safety Information

The most important safety information patients should know about
Gazyva

Patients must tell their doctor right away about any side effect they
experience. Gazyva can cause side effects that can become serious or
life threatening, including:

  • Hepatitis B Virus (HBV): Hepatitis B can cause liver failure
    and death. If the patient has a history of hepatitis B infection,
    Gazyva could cause it to return. Patients should not receive Gazyva if
    they have active hepatitis B liver disease. The patient’s doctor or
    healthcare team will need to screen them for hepatitis B before, and
    monitor the patient for hepatitis during and after, their treatment
    with Gazyva. Sometimes this will require treatment for hepatitis B.
    Symptoms of hepatitis include: worsening of fatigue and yellow
    discoloration of skin or eyes
  • Progressive Multifocal Leukoencephalopathy (PML): PML is a rare
    and serious brain infection caused by a virus. PML can be fatal. The
    patient’s weakened immune system could put them at risk. The patient’s
    doctor will watch for symptoms. Symptoms of PML include: confusion,
    difficulty talking or walking, dizziness or loss of balance, and
    vision problems

Who should not receive Gazyva:

Patients should NOT receive Gazyva if they
have had an allergic reaction (e.g., anaphylaxis or serum sickness) to
Gazyva. Patients must tell their healthcare provider if they
have had an allergic reaction to obinutuzumab or any other ingredients
in Gazyva in the past.

Additional possible serious side effects of Gazyva:

Patients must tell their doctor right away about any side effect they
experience. Gazyva can cause side effects that may become severe or life
threatening, including:

  • Infusion Reactions: These side effects may occur
    during or within 24 hours of any Gazyva infusion. Some infusion
    reactions can be serious, including, but not limited to, severe
    allergic reactions (anaphylaxis), acute life-threatening breathing
    problems, or other life-threatening infusion reactions. If the patient
    has a reaction, the infusion is either slowed or stopped until their
    symptoms are resolved. Most patients are able to complete infusions
    and receive medication again. However, if the infusion reaction is
    life threatening, the infusion of Gazyva will be permanently stopped.
    The patient’s healthcare team will take steps to help lessen any side
    effects the patient may have to the infusion process. The patient may
    be given medicines to take before each Gazyva treatment. Symptoms of
    infusion reactions may include: fast heartbeat, tiredness, dizziness,
    headache, redness of the face, nausea, chills, fever, vomiting,
    diarrhea, rash, high blood pressure, low blood pressure, difficulty
    breathing, and chest discomfort
  • Hypersensitivity Reactions Including Serum Sickness: Some
    patients receiving Gazyva may have severe or life-threatening allergic
    reactions. This reaction may be severe, may happen during or after an
    infusion, and may affect many areas of the body. If an allergic
    reaction occurs, the patient’s doctor will stop the infusion and
    permanently discontinue Gazyva
  • Tumor Lysis Syndrome (TLS): Tumor lysis syndrome, including
    fatal cases, has been reported in patients receiving Gazyva. Gazyva
    works to break down cancer cells quickly. As cancer cells break apart,
    their contents are released into the blood. These contents may cause
    damage to organs and the heart, and may lead to kidney failure
    requiring the need for dialysis treatment. The patient’s doctor may
    prescribe medication to help prevent TLS. The patient’s doctor will
    also conduct regular blood tests to check for TLS. Symptoms of TLS may
    include nausea, vomiting, diarrhea, and tiredness
  • Infections: While the patient is taking Gazyva, they may
    develop infections. Some of these infections may be fatal and severe,
    so the patient should be sure to talk to their doctor if they think
    they have an infection. Patients administered Gazyva in combination
    with chemotherapy, followed by Gazyva alone are at a high risk of
    infections during and after treatment. Patients with a history of
    recurring or chronic infections may be at an increased risk of
    infection. Patients with an active infection should not be treated
    with Gazyva. Patients taking Gazyva plus bendamustine may be at higher
    risk for fatal or severe infections compared to patients taking Gazyva
    plus CHOP or CVP
  • Low White Blood Cell Count: When the patient has an abnormally
    low count of infection-fighting white blood cells, it is called
    neutropenia. While the patient is taking Gazyva, their doctor will do
    blood work to check their white blood cell count. Severe and
    life-threatening neutropenia can develop during or after treatment
    with Gazyva. Some cases of neutropenia can last for more than one
    month. If the patient’s white blood cell count is low, their doctor
    may prescribe medication to help prevent infections
  • Low Platelet Count: Platelets help stop bleeding or blood loss.
    Gazyva may reduce the number of platelets the patient has in their
    blood; having low platelet count is called thrombocytopenia. This may
    affect the clotting process. While the patient is taking Gazyva, their
    doctor will do blood work to check their platelet count. Severe and
    life-threatening thrombocytopenia can develop during treatment with
    Gazyva. Fatal bleeding events have occurred in patients treated with
    Gazyva. If the patient’s platelet count gets too low, their treatment
    may be delayed or reduced

The most common side effects of Gazyva in CLL were infusion reactions,
low white blood cell counts, low platelet counts, low red blood cell
counts, fever, cough, nausea, and diarrhea.

The safety of Gazyva was evaluated based on 392 patients with relapsed
or refractory NHL, including FL (81 percent), small lymphocytic lymphoma
(SLL) and marginal zone lymphoma (MZL) (a disease for which Gazyva is
not indicated), who did not respond to or progressed within 6 months of
treatment with rituximab product or a rituximab product-containing
regimen. In patients with follicular lymphoma, the profile of side
effects that were seen were consistent with the overall population who
had NHL. The most common side effects of Gazyva were infusion reactions,
low white blood cell counts, nausea, fatigue, cough, diarrhea,
constipation, fever, low platelet counts, vomiting, upper respiratory
tract infection, decreased appetite, joint or muscle pain, sinusitis,
low red blood cell counts, general weakness and urinary tract infection.

A randomized, open-label multicenter trial (GALLIUM) evaluated the
safety of Gazyva as compared to rituximab product in 1,385 patients with
previously untreated follicular lymphoma (86%) or marginal zone lymphoma
(14%). The most common side effects of Gazyva were infusion reactions,
low white blood cell count, upper respiratory tract infection, cough,
constipation and diarrhea.

Before receiving Gazyva, patients should talk to their doctor about:

  • Immunizations: Before receiving Gazyva therapy, the patient
    should tell their healthcare provider if they have recently received
    or are scheduled to receive a vaccine. Patients who are treated with
    Gazyva should not receive live vaccines
  • Pregnancy: The patient should tell their doctor if they are
    pregnant, think that they might be pregnant, plan to become pregnant,
    or are breastfeeding. Gazyva may harm their unborn baby. The patient
    should speak to their doctor about using Gazyva while they are
    pregnant. The patient should talk to their doctor or their child’s
    doctor about the safety and timing of live virus vaccinations to their
    infant if they received Gazyva during pregnancy. It is not known if
    Gazyva may pass into the patient’s breast milk. The patient should
    speak to their doctor about using Gazyva if they are breastfeeding

Patients should tell their doctor about any side effects.

These are not all of the possible side effects of Gazyva. For more
information, patients should ask their doctor or pharmacist.

Gazyva is available by prescription only.

Report side effects to the FDA at (800) FDA-1088, or http://www.fda.gov/medwatch .
Report side effects to Genentech at (888) 835-2555.

Please visit http://www.Gazyva.com
for the Gazyva full Prescribing Information, including BOXED
WARNINGS, for additional Important Safety Information.

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.

References

1. A. de Zubiria Salgado and C. Herrera-Diaz, Lupus Nephritis: An
Overview of Recent Findings. Autoimmune Diseases, vol. 2012, Article ID
849684, 221 pages, 2012. doi:10.1155/2012/849684

2. R. Saxena et al. Lupus Nephritis: Current Update. Arthritis Research
& Therapy, 2011, 13:240. doi:10.1186/ar3378

3. Lupus Foundation of America. Lupus Facts and Statistics. https://www.lupus.org/resources/lupus-facts-and-statistics
(Last accessed May 6, 2019)

4. Lupus Research Alliance. Lupus Fact Sheet. http://www.lupusresearch.org/wp-content/uploads/2017/09/Lupus-Fact-Sheet.pdf
(Last accessed May 6, 2019)

Contacts

Media Contact:
Allison Neves, (650) 467-6800

Advocacy
Contact:
Jocelyn Ashford (650) 866-7579

Investor
Contacts:
Lisa Tuomi (650) 467-8737
Karl Mahler +41 61 687 8503

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