2seventy and Bristol Myers Squibb discontinue
enrollment in Phase 3 KarMMa-9 study
Decision results in over $80 million in
anticipated cost savings for 2seventy over the next several years
and accelerates path to breakeven in 2025
Expanded 3L+ label drives re-acceleration in
Abecma U.S. revenues with third quarter revenue expected to grow
approximately 30% from second quarter revenue of $54 million
2seventy bio, Inc. (Nasdaq: TSVT) today announced that the
Company, in partnership with study sponsor Bristol Myers Squibb
(BMS), will discontinue enrollment in its ongoing Phase 3 KarMMa-9
study evaluating Abecma® (idecabtagene vicleucel; ide-cel) with
lenalidomide maintenance versus lenalidomide maintenance alone in
patients with newly diagnosed multiple myeloma (NDMM) who have
suboptimal response to autologous stem cell transplant.
“With a greatly improved NDMM treatment landscape and following
our rigorous review of the business case for the KarMMa-9 study, we
have decided to discontinue enrollment in this Phase 3 study,” said
Chip Baird, chief executive officer, 2seventy bio. “Abecma
continues to show encouraging signs of growth with an expanded
label in the third line and a differentiated safety profile.
Consistent with our focus on capital allocation and creating value
for all stakeholders, we anticipate this decision will conserve
over $80 million in near-term expenditures and accelerate our path
to breakeven in 2025. We will continue to look for ways to optimize
our business for growth while remaining true to our mission of
delivering more time for patients.”
2seventy and its partner, BMS, remain committed to and strongly
believe in the value that Abecma brings to patients and the
important role it plays in the multiple myeloma treatment paradigm.
Abecma has a differentiated safety profile and a competitive
efficacy profile, particularly when combined with effective
bridging therapies. The partners plan to continue expanding the
reach of Abecma to as many multiple myeloma patients as
possible.
Anna Truppel-Hartmann, chief medical officer, 2seventy bio,
added, “Since we initiated the Phase 3 KarMMa-9 study in NDMM based
on the positive data generated in a similar patient population in
the KarMMa-2 cohort 2c study, the NDMM treatment landscape has
improved considerably with the increasing use of quadruplet therapy
induction, incorporation of more aggressive consolidation
therapies, and the ongoing optimization of maintenance therapy
regimens. As a result, there are considerably fewer eligible
patients than when the study was first designed. We celebrate this
progress in treatment options for patients and will continue to
focus on serving patients with a high unmet need who will benefit
most from Abecma. We would like to extend our deepest gratitude to
the patients, their families, and the investigators and study staff
who participated in this trial.”
Commercial Progress and Guidance
2seventy is pleased to report continued positive momentum in
Abecma’s expected return to growth in the earlier line setting
following the FDA’s approval in April 2024. The Company expects
third quarter Abecma U.S. revenue growth of approximately 30% from
second quarter revenue of $54 million. Demand, as measured by new
patients undergoing apheresis in the third quarter, is also
expected to reflect double-digit growth when compared to the second
quarter of 2024. The Company remains committed to driving the
continued success of Abecma in 2024 and beyond.
2seventy bio and BMS share equally in all profits and losses
related to development, manufacturing, and commercialization of
Abecma in the U.S.
ABECMA U.S. INDICATION
ABECMA is a B-cell maturation antigen (BCMA)-directed
genetically modified autologous T cell immunotherapy indicated for
the treatment of adult patients with relapsed or refractory
multiple myeloma after two or more prior lines of therapy including
an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38
monoclonal antibody.
U.S. Important Safety
Information
BOXED WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC
TOXICITIES, HLH/MAS, PROLONGED CYTOPENIA and SECONDARY
HEMATOLOGICAL MALIGNANCIES
- Cytokine Release Syndrome (CRS), including fatal or
life-threatening reactions, occurred in patients following
treatment with ABECMA. Do not administer ABECMA to patients with
active infection or inflammatory disorders. Treat severe or
life-threatening CRS with tocilizumab or tocilizumab and
corticosteroids.
- Neurologic Toxicities, which may be severe or life-threatening,
occurred following treatment with ABECMA, including concurrently
with CRS, after CRS resolution, or in the absence of CRS. Monitor
for neurologic events after treatment with ABECMA. Provide
supportive care and/or corticosteroids as needed.
- Hemophagocytic Lymphohistiocytosis/Macrophage Activation
Syndrome (HLH/MAS) including fatal and life-threatening reactions,
occurred in patients following treatment with ABECMA. HLH/MAS can
occur with CRS or neurologic toxicities.
- Prolonged Cytopenia with bleeding and infection, including
fatal outcomes following stem cell transplantation for
hematopoietic recovery, occurred following treatment with
ABECMA.
- T cell malignancies have occurred following treatment of
hematologic malignancies with BCMA- and CD19-directed genetically
modified autologous T cell immunotherapies, including ABECMA
- ABECMA is available only through a restricted program under a
Risk Evaluation and Mitigation Strategy (REMS) called the ABECMA
REMS.
Warnings and Precautions:
Early Death: In KarMMa-3, a randomized (2:1), controlled
trial, a higher proportion of patients experienced death within 9
months after randomization in the ABECMA arm (45/254; 18%) compared
to the standard regimens arm (15/132; 11%). Early deaths occurred
in 8% (20/254) and 0% prior to ABECMA infusion and standard regimen
administration, respectively, and 10% (25/254) and 11% (15/132)
after ABECMA infusion and standard regimen administration,
respectively. Out of the 20 deaths that occurred prior to ABECMA
infusion, 15 occurred from disease progression, 3 occurred from
adverse events and 2 occurred from unknown causes. Out of the 25
deaths that occurred after ABECMA infusion, 10 occurred from
disease progression, 11 occurred from adverse events, and 4
occurred from unknown causes.
Cytokine Release Syndrome (CRS): CRS, including fatal or
life-threatening reactions, occurred following treatment with
ABECMA. Among patients receiving ABECMA for relapsed refractory
multiple myeloma in the KarMMa and KarMMa-3 studies (N=349), CRS
occurred in 89% (310/349), including ≥ Grade 3 CRS (Lee grading
system) in 7% (23/349) of patients and Grade 5 CRS in 0.9% (3/349)
of patients. The median time-to-onset of CRS, any grade, was 1 day
(range: 1 to 27 days), and the median duration of CRS was 5 days
(range: 1 to 63 days). In the pooled studies, the rate of ≥Grade 3
CRS was 10% (7/71) for patients treated in dose range of 460 to 510
x 106 CAR-positive T cells and 5.4% (13/241) for patients treated
in dose range of 300 to 460 x 106 CAR-positive T cells.
The most common manifestations of CRS (greater than or equal to
10%) included pyrexia (87%), hypotension (30%), tachycardia (26%),
chills (19%), hypoxia (16%). Grade 3 or higher events that may be
associated with CRS include hypotension, hypoxia,
hyperbilirubinemia, hypofibrinogenemia, ARDS, atrial fibrillation,
hepatocellular injury, metabolic acidosis, pulmonary edema,
coagulopathy, renal failure, multiple organ dysfunction syndrome
and HLH/MAS.
Identify CRS based on clinical presentation. Evaluate for and
treat other causes of fever, hypoxia, and hypotension. CRS has been
reported to be associated with findings of HLH/MAS, and the
physiology of the syndromes may overlap. HLH/MAS is a potentially
life-threatening condition. In patients with progressive symptoms
of CRS or refractory CRS despite treatment, evaluate for evidence
of HLH/MAS.
Of the 349 patients who received ABECMA in clinical trials, 226
(65%) patients received tocilizumab; 39% (135/349) received a
single dose, while 26% (91/349) received more than 1 dose of
tocilizumab. Overall, 24% (82/349) of patients received at least 1
dose of corticosteroids for treatment of CRS. Almost all patients
who received corticosteroids for CRS also received tocilizumab. For
patients treated in dose range of 460 to 510 x 106 CAR-positive T
cells, 76% (54/71) of patients received tocilizumab and 35% (25/71)
received at least 1 dose of corticosteroids for treatment of CRS.
For patients treated in dose range of 300 to 460 x 106 CAR-positive
T cells, 63% (152/241) of patients received tocilizumab and 20%
(49/241) received at least 1 dose of corticosteroid for treatment
of CRS.
Monitor patients at least daily for 7 days following ABECMA
infusion at the REMS-certified healthcare facility for signs or
symptoms of CRS and monitor patients for signs or symptoms of CRS
for at least 4 weeks after ABECMA infusion. At the first sign of
CRS, institute treatment with supportive care, tocilizumab and/or
corticosteroids as indicated. Ensure that a minimum of 2 doses of
tocilizumab are available prior to infusion of ABECMA. Counsel
patients to seek immediate medical attention should signs or
symptoms of CRS occur at any time.
Neurologic Toxicities: Neurologic toxicities, including
immune-effector cell-associated neurotoxicity (ICANS), which may be
severe or life-threatening, occurred concurrently with CRS, after
CRS resolution, or in the absence of CRS following treatment with
ABECMA.
In patients receiving ABECMA in the KarMMa and KarMMa-3 studies,
CAR T cell-associated neurotoxicity occurred in 40% (139/349),
including Grade 3 in 4% (14/349) and Grade 4 in 0.6% (2/349) of
patients. The median time to onset of neurotoxicity was 2 days
(range: 1 to 148 days). The median duration of CAR T
cell-associated neurotoxicity was 8 days (range: 1 to 720 days) in
all patients including those with ongoing neurologic events at the
time of death or data cut off. CAR T cell-associated neurotoxicity
resolved in 123 of 139 (88%) patients and median time to resolution
was 5 days (range: 1 to 245 days). One-hundred and thirty four out
of 349 (38%) patients with neurotoxicity had CRS. The onset of
neurotoxicity during CRS was observed in 93 patients, before the
onset of CRS in 12 patients, and after the CRS event in 29
patients. The rate of Grade 3 or 4 CAR T cell-associated
neurotoxicity was 5.6% (4/71) and 3.7% (9/241) for patients treated
in dose range of 460 to 510 x 106 CAR-positive T cells and 300 to
460 x 106 CAR-positive T cells, respectively. The most frequent
(greater than or equal to 5%) manifestations of CAR T
cell-associated neurotoxicity include encephalopathy (21%),
headache (15%), dizziness (8%), delirium (6%), and tremor (6%).
At the safety update for KarMMa-3 study, one patient developed
fatal neurotoxicity 43 days after ABECMA. In KarMMa, one patient
had ongoing Grade 2 neurotoxicity at the time of death. Two
patients had ongoing Grade 1 tremor at the time of data cutoff.
Cerebral edema has been associated with ABECMA in a patient in
another study in multiple myeloma. Grade 3 myelitis and Grade 3
parkinsonism have occurred after treatment with ABECMA in another
study in multiple myeloma.
Monitor patients at least daily for 7 days following ABECMA
infusion at the REMS-certified healthcare facility for signs or
symptoms of neurologic toxicities and monitor patients for signs or
symptoms of neurologic toxicities for at least 4 weeks after ABECMA
infusion and treat promptly. Rule out other causes of neurologic
symptoms. Neurologic toxicity should be managed with supportive
care and/or corticosteroids as needed. Counsel patients to seek
immediate medical attention should signs or symptoms occur at any
time.
Hemophagocytic Lymphohistiocytosis (HLH)/Macrophage
Activation Syndrome (MAS): In patients receiving ABECMA in the
KarMMa and KarMMa-3 studies, HLH/MAS occurred in 2.9% (10/349) of
patients. All events of HLH/MAS had onset within 10 days of
receiving ABECMA, with a median onset of 6.5 days (range: 4 to 10
days) and occurred in the setting of ongoing or worsening CRS. Five
patients with HLH/MAS had overlapping neurotoxicity. The
manifestations of HLH/MAS include hypotension, hypoxia, multiple
organ dysfunction, renal dysfunction and cytopenia.
In KarMMa-3, one patient had Grade 5, two patients had Grade 4
and two patients had Grade 3 HLH/MAS. The patient with Grade 5
HLH/MAS also had Grade 5 candida sepsis and Grade 5 CRS. In another
patient who died due to stroke, the Grade 4 HLH/MAS had resolved
prior to death. Two cases of Grade 3 and one case of Grade 4
HLH/MAS had resolved.
In KarMMa, one patient treated in the 300 x 106 CAR-positive T
cells dose cohort developed fatal multi-organ HLH/MAS with CRS. In
another patient with fatal bronchopulmonary aspergillosis, HLH/MAS
was contributory to the fatal outcome. Three cases of Grade 2
HLH/MAS resolved.
HLH/MAS is a potentially life-threatening condition with a high
mortality rate if not recognized early and treated. Treatment of
HLH/MAS should be administered per institutional guidelines.
ABECMA REMS: Due to the risk of CRS and neurologic
toxicities, ABECMA is available only through a restricted program
under a Risk Evaluation and Mitigation Strategy (REMS) called the
ABECMA REMS. Further information is available at www.AbecmaREMS.com
or contact Bristol-Myers Squibb at 1-866-340-7332.
Hypersensitivity Reactions: Allergic reactions may occur
with the infusion of ABECMA. Serious hypersensitivity reactions,
including anaphylaxis, may be due to dimethyl sulfoxide (DMSO) in
ABECMA.
Infections: ABECMA should not be administered to patients
with active infections or inflammatory disorders. Severe,
life-threatening, or fatal infections occurred in patients after
ABECMA infusion.
In all patients receiving ABECMA in the KarMMa and KarMMa-3
studies, infections (all grades) occurred in 61% of patients. Grade
3 or 4 infections occurred in 21% of patients. Grade 3 or 4
infections with an unspecified pathogen occurred in 12%, viral
infections in 7%, bacterial infections in 4.3%, and fungal
infections in 1.4% of patients. Overall, 15 patients had Grade 5
infections (4.3%); 8 patients (2.3%) with infections of pathogen
unspecified, 3 patients (0.9%) with fungal infections, 3 patients
(0.9%) with viral infections, and 1 patient (0.3%) with bacterial
infection.
Monitor patients for signs and symptoms of infection before and
after ABECMA infusion and treat appropriately. Administer
prophylactic, pre-emptive, and/or therapeutic antimicrobials
according to standard institutional guidelines.
Febrile neutropenia was observed in 38% (133/349) of patients
after ABECMA infusion and may be concurrent with CRS. In the event
of febrile neutropenia, evaluate for infection and manage with
broad-spectrum antibiotics, fluids, and other supportive care as
medically indicated.
Viral Reactivation: Cytomegalovirus (CMV) infection resulting in
pneumonia and death has occurred following ABECMA administration.
Monitor and treat for CMV reactivation in accordance with clinical
guidelines. Hepatitis B virus (HBV) reactivation, in some cases
resulting in fulminant hepatitis, hepatic failure, and death, can
occur in patients treated with drugs directed against plasma cells.
Perform screening for CMV, HBV, hepatitis C virus (HCV), and human
immunodeficiency virus (HIV) in accordance with clinical guidelines
before collection of cells for manufacturing. Consider antiviral
therapy to prevent viral reactivation per local institutional
guidelines/clinical practice.
Prolonged Cytopenias: In patients receiving ABECMA in the
KarMMa and KarMMa-3 studies, 40% of patients (139/349) experienced
prolonged Grade 3 or 4 neutropenia and 42% (145/349) experienced
prolonged Grade 3 or 4 thrombocytopenia that had not resolved by
Month 1 following ABECMA infusion. In 89% (123/139) of patients who
recovered from Grade 3 or 4 neutropenia after Month 1, the median
time to recovery from ABECMA infusion was 1.9 months. In 76%
(110/145) of patients who recovered from Grade 3 or 4
thrombocytopenia, the median time to recovery was 1.9 months. Five
patients underwent stem cell therapy for hematopoietic
reconstitution due to prolonged cytopenia. The rate of Grade 3 or 4
thrombocytopenia was 62% (44/71) and 56% (135/241) for patients
treated in dose range of 460 to 510 x 106 CAR-positive T cells and
300 to 460 x 106 CAR-positive T cells, respectively.
Monitor blood counts prior to and after ABECMA infusion. Manage
cytopenia with myeloid growth factor and blood product transfusion
support according to local institutional guidelines.
Hypogammaglobulinemia: In all patients receiving ABECMA
in the KarMMa and KarMMa-3 studies, hypogammaglobulinemia was
reported as an adverse event in 13% (46/349) of patients;
laboratory IgG levels fell below 500 mg/dL after infusion in 37%
(130/349) of patients treated with ABECMA.
Hypogammaglobulinemia either as an adverse reaction or
laboratory IgG level below 500 mg/dL after infusion occurred in 45%
(158/349) of patients treated with ABECMA. Forty-one percent of
patients received intravenous immunoglobulin (IVIG) post-ABECMA for
serum IgG <400 mg/dL.
Monitor immunoglobulin levels after treatment with ABECMA and
administer IVIG for IgG <400 mg/dl. Manage appropriately per
local institutional guidelines, including infection precautions and
antibiotic or antiviral prophylaxis.
Use of Live Vaccines: The safety of immunization with live viral
vaccines during or after ABECMA treatment has not been studied.
Vaccination with live virus vaccines is not recommended for at
least 6 weeks prior to the start of lymphodepleting chemotherapy,
during ABECMA treatment, and until immune recovery following
treatment with ABECMA.
Secondary Malignancies: Patients treated with ABECMA may
develop secondary malignancies. In KarMMa-3, myeloid neoplasms
(four cases of myelodysplastic syndrome and one case of acute
myeloid leukemia) occurred in 2.2% (5/222) of patients following
treatment with ABECMA compared to none in the standard regimens arm
at the time of the safety update. The median time to onset of
myeloid neoplasm from ide-cel infusion was 338 days (Range: 277 to
794 days). Three of these five patients have died following the
development of myeloid neoplasm. One out of the five cases of
myeloid neoplasm occurred after initiation of subsequent
antimyeloma therapy.
T cell malignancies have occurred following treatment of
hematologic malignancies with BCMA- and CD19-directed genetically
modified autologous T cell immunotherapies, including ABECMA.
Mature T cell malignancies, including CAR-positive tumors, may
present as soon as weeks following infusion, and may include fatal
outcomes.
Monitor life-long for secondary malignancies. In the event that
a secondary malignancy occurs, contact Bristol-Myers Squibb at
1‑888‑805‑4555 for reporting and to obtain instructions on
collection of patient samples for testing of secondary
malignancy.
Effects on Ability to Drive and Operate Machinery: Due to
the potential for neurologic events, including altered mental
status or seizures, patients receiving ABECMA are at risk for
altered or decreased consciousness or coordination in the 8 weeks
following ABECMA infusion. Advise patients to refrain from driving
and engaging in hazardous occupations or activities, such as
operating heavy or potentially dangerous machinery, during this
initial period.
Adverse Reactions: The most common nonlaboratory adverse
reactions (incidence greater than or equal to 20%) include pyrexia,
CRS, hypogammaglobulinemia, infections – pathogen unspecified,
musculoskeletal pain, fatigue, febrile neutropenia, hypotension,
tachycardia, diarrhea, nausea, headache, chills, upper respiratory
tract infection, encephalopathy, edema, dyspnea and viral
infections.
Please see full Prescribing Information, including Boxed
WARNINGS and Medication Guide.
About Bristol Myers Squibb and 2seventy bio
Abecma is being jointly developed and commercialized in the U.S.
as part of a Co-Development, Co-Promotion, and Profit Share
Agreement between Bristol Myers Squibb and 2seventy bio. Bristol
Myers Squibb assumes sole responsibility for Abecma drug product
manufacturing and commercialization outside of the U.S. The
companies’ broad clinical development program for Abecma includes
ongoing and planned clinical studies (KarMMa-2, KarMMa-3) in
earlier lines of treatment for patients with multiple myeloma. For
more information visit clinicaltrials.gov.
About 2seventy bio
Our name, 2seventy bio, reflects why we do what we do - TIME.
Cancer rips time away, and our goal is to work at the maximum speed
of translating human thought into action – 270 miles per hour – to
give the people we serve more time. With a deep understanding of
the human body’s immune response to tumor cells and how to
translate cell therapies into practice, we’re applying this
knowledge to deliver the first FDA-approved CAR T cell therapy for
multiple myeloma to as many patients as possible. Importantly, we
remain focused on accomplishing our mission by staying genuine and
authentic to our “why” and keeping our people and culture top of
mind every day. For more information, visit
www.2seventybio.com.
Follow 2seventy bio on social media: X (Twitter) and
LinkedIn.
2seventy bio is a trademark of 2seventy bio, Inc.
Cautionary Note Regarding Forward-Looking Statements
This release contains “forward-looking statements” within the
meaning of applicable laws and regulations. These statements
include, but are not limited to: statements about the
discontinuation of the ongoing Phase 3 KarMMa-9 study, including
the potential cost savings; statements regarding expected ABECMA
(ide-cel) U.S. revenue and demand in the third quarter of 2024;
statements regarding expected benefits from our strategic
collaboration with BMS; statements about the efficacy and perceived
therapeutic benefits of ABECMA; statements regarding our financial
condition, expenses, results of operations, and expectations
regarding our path to breakeven; and statements about our business
plans and strategies. Any forward-looking statements in this press
release are based on management's current expectations and beliefs
and are subject to a number of risks, uncertainties and important
factors that may cause actual events or results to differ
materially from those expressed or implied by any forward-looking
statements contained in this press release, including, without
limitation, our limited independent operating history and the risk
that our accounting and other management systems may not be
prepared to meet the financial reporting and other requirements of
operating as an independent public company; the risk that Abecma
will not be as commercially successful as we may anticipate; the
risk that our strategic realignment to focus on the development and
commercialization of Abecma may not be as successful as
anticipated, may fail to achieve the anticipated cost savings, and
may cause disruptions in our business that could make it difficult
to achieve our strategic objectives; and the risk that we are
unable to manage our operating expenses or cash use for operations.
For a discussion of other risks and uncertainties, and other
important factors, any of which could cause our actual results to
differ from those contained in the forward-looking statements, see
the section entitled “Risk Factors” in our annual Report on Form
10-K for the year ended December 31, 2023, as supplemented and/or
modified by any other subsequent filings that we have made and will
make with the Securities and Exchange Commission in the future. All
information in this press release is as of the date of this
release, and we undertake no duty to update this information unless
required by law.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20240925722000/en/
Investors and Media: Vicki Eatwell, CFO
vicki.eatwell@2seventybio.com
Morgan (Adams) Shields Morgan.adams@2seventybio.com
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