Full Press Release Details
Rigel Announces U.S. FDA
Approval of REZLIDHIA (olutasidenib) for the Treatment of Adult
Patients with Relapsed or Refractory Acute Myeloid Leukemia with
REZLIDHIA is a potentially
market-leading, oral, mutant isocitrate dehydrogenase-1 (mIDH1) inhibitor
Phase 2 registrational data
supporting the approval showed a 35% CR+CRh rate in mIDH1 R/R AML patients with a median duration of response of 25.9 months
Conference call and webcast
to be held today at 6:30 p.m ET
SOUTH SAN FRANCISCO, Calif., Dec. 1, 2022 /PRNewswire/
-- Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) today announced that the U.S. Food and Drug Administration (FDA) has approved REZLIDHIA
(olutasidenib) capsules for the treatment of adult patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) with a
susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test. REZLIDHIA is an oral, small molecule, inhibitor
of mutated IDH1 designed to bind to and inhibit mIDH1 to reduce 2-hydroxyglutarate levels and restore normal cellular differentiation
"REZLIDHIA is a novel, non-intensive monotherapy
treatment in the relapsed/refractory AML setting demonstrating a CR+CRh rate of 35% in patients with over 90% of those responders in complete
remission. The 25.9 months median duration of CR+CRh is a clinically meaningful improvement for AML patients and appears to be longer
than currently available treatment options," said Jorge E. Cortes, M.D., Director, Georgia Cancer Center, Cecil F. Whitaker Jr.,
GRA Eminent Scholar Chair in Cancer, and Phase 2 trial investigator. "Given the limited treatment options for adult patients with
mIDH1 R/R AML, who typically have a poor prognosis, REZLIDHIA may provide an effective, new treatment option with a well characterized
The FDA approval was supported by data from the open-label
Phase 2 registrational study evaluating REZLIDHIA monotherapy at a dose of 150 mg twice daily in 153 mIDH1 R/R AML patients. The efficacy-evaluable
population was 147 patients who initiated REZLIDHIA at least six months prior to the interim analysis cutoff date of June 18, 2021, and
who had a centrally confirmed IDH1 mutation. The primary endpoint was a composite of a complete remission (CR) plus a complete remission
with partial hematological recovery (CRh). CRh is defined as less than 5% blasts in the bone marrow, no evidence of disease, and partial
recovery of peripheral blood counts (platelets >50,000/microliter and absolute neutrophil count >500/microliter).
Results from the trial demonstrated a 35% (51/147) CR+CRh rate in
mIDH1 R/R AML patients, with a median duration of response of 25.9 months. The median time to CR or CRh
was 1.9 months. Of the patients who achieved the primary endpoint of CR+CRh, 92% (47/51) were CR
with a median duration of response of 28.1 months. REZLIDHIA was well tolerated in the study with an adverse event profile
largely characteristic of symptoms or conditions experienced by patients with AML undergoing treatment. Differentiation syndrome was
observed in 16% of patients and was manageable in most cases with dose interruption and corticosteroids. Hepatotoxicity, presenting
as increases in liver function parameters, occurred in 23% of patients and most cases were manageable with dose modifications.
"We are delighted by the approval of REZLIDHIA
based on the strength of data supporting the efficacy and safety of the product," said Raul Rodriguez, Rigel's president and CEO.
"REZLIDHIA provides a new and important, oral therapy option for patients who typically have a poor clinical outcome. Additionally,
this approval greatly strengthens and expands Rigel's commercial hematology-oncology portfolio. I would like to extend our sincerest
thanks to all the patients, their families and caregivers, the doctors, the FDA, and our team members who have all contributed to the
approval of REZLIDHIA."
In August 2022, Rigel and Forma Therapeutics, Inc.
announced they entered an exclusive, worldwide license agreement to develop, manufacture and commercialize REZLIDHIA. Under the terms
of the agreement, Rigel will be responsible for the launch and commercialization of REZLIDHIA in the U.S., and intends to work with potential
partners to further develop and commercialize the product outside the U.S.
Conference Call and Webcast Today at 6:30 PM Eastern
Rigel will hold a live conference call and webcast
today at 6:30 p.m. Eastern Time (3:30 p.m. Pacific Time) to discuss the FDA approval of REZLIDHIA.
Participants can access the live conference call by dialing
877-407-3088 (domestic) or 201389-0927 (international). The conference call will also be webcast live and can be accessed from
the Investor Relations section of the company's website at www.rigel.com. The webcast will be archived and available for
replay after the call via the Rigel website.
Acute myeloid leukemia (AML) is a rapidly progressing cancer of the
blood and bone marrow that affects myeloid cells, which normally develop into various types of mature blood cells. AML occurs primarily
in adults and accounts for about 1 percent of all adult cancers. The American Cancer Society estimates that in the United States alone,
there will be about 20,050 new cases, most in adults, in 2022.1
Relapsed AML affects about half of all patients who, following treatment
and remission, experience a return of leukemia cells in the bone marrow.2 Refractory
AML, which affects between 10 and 40 percent of newly diagnosed patients, occurs when a patient fails to achieve remission even after
intensive treatment.3 Quality of life declines for patients with each successive line
of treatment for AML, and well-tolerated treatments in relapsed or refractory disease remain an unmet need.
REZLIDHIA is indicated for the treatment of adult patients with
relapsed or refractory acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Differentiation Syndrome
REZLIDHIA can cause differentiation syndrome. In
the clinical trial of REZLIDHIA in patients with relapsed or refractory AML, differentiation syndrome occurred in 16% of patients, with
grade 3 or 4 differentiation syndrome occurring in 8% of patients treated, and fatalities in 1% of patients. Differentiation syndrome
is associated with rapid proliferation and differentiation of myeloid cells and may be life-threatening or fatal. Symptoms of differentiation
syndrome in patients treated with REZLIDHIA included leukocytosis, dyspnea, pulmonary infiltrates/pleuropericardial effusion, kidney injury,
fever, edema, pyrexia, and weight gain. Of the 25 patients who experienced differentiation syndrome, 19 (76%) recovered after treatment
or after dose interruption of REZLIDHIA. Differentiation syndrome occurred as early as 1 day and up to 18 months after REZLIDHIA initiation
and has been observed with or without concomitant leukocytosis.
If differentiation syndrome is suspected, temporarily
withhold REZLIDHIA and initiate systemic corticosteroids (e.g., dexamethasone 10 mg IV every 12 hours) for a minimum of 3 days and until
resolution of signs and symptoms. If concomitant leukocytosis is observed, initiate treatment with hydroxyurea, as clinically indicated.
Taper corticosteroids and hydroxyurea after resolution of symptoms. Differentiation syndrome may recur with premature discontinuation
of corticosteroids and/or hydroxyurea treatment. Institute supportive measures and hemodynamic monitoring until improvement; withhold
dose of REZLIDHIA and consider dose reduction based on recurrence.
REZLIDHIA can cause hepatotoxicity, presenting as increased
alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), increased blood alkaline phosphatase, and/or elevated
bilirubin. Of 153 patients with relapsed or refractory AML who received REZLIDHIA, hepatotoxicity occurred in 23% of patients; 13%
experienced grade 3 or 4 hepatotoxicity. One patient treated with REZLIDHIA in combination with azacitidine in the clinical trial, a
combination for which REZLIDHIA is not indicated, died from complications of drug-induced liver injury. The median time to onset of
hepatotoxicity in patients with relapsed or refractory AML treated with REZLIDHIA was 1.2 months (range: 1 day to 17.5 months) after
REZLIDHIA initiation, and the median time to resolution was 12 days (range: 1 day to 17 months). The most common hepatotoxicities
were elevations of ALT, AST, blood alkaline phosphatase, and blood bilirubin.
Monitor patients frequently for clinical symptoms
of hepatic dysfunction such as fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice. Obtain baseline liver function
tests prior to initiation of REZLIDHIA, at least once weekly for the first two months, once every other week for the third month, once
in the fourth month, and once every other month for the duration of therapy. If hepatic dysfunction occurs, withhold, reduce, or permanently
discontinue REZLIDHIA based on recurrence/severity.
The most common ( 20%) adverse reactions, including
laboratory abnormalities, were aspartate aminotransferase increased, alanine aminotransferase increased, potassium decreased, sodium decreased,
alkaline phosphatase increased, nausea, creatinine increased, fatigue/malaise, arthralgia, constipation, lymphocytes increased, bilirubin
increased, leukocytosis, uric acid increased, dyspnea, pyrexia, rash, lipase increased, mucositis, diarrhea and transaminitis.
Advise women not to breastfeed during treatment with
REZLIDHIA and for 2 weeks after the last dose.
No overall differences in effectiveness
were observed between patients 65 years and older and younger patients. Compared to patients younger than 65 years of age, an increase
in incidence of hepatotoxicity and hypertension was observed in patients 65 years of age.