* LEGEND achieved its primary efficacy endpoint by significantly lowering
HbA1c level in both the lanifibranor arm and in the lanifibranor with
empagliflozin arm compared to placebo.
* Statistical significance was also achieved on several markers of liver
injury, markers of glucose and lipid metabolism, as well as hepatic
steatosis.
* Patients treated with lanifibranor in combination with empagliflozin
maintained a stable weight throughout the 24 weeks study, addressing the
moderate, metabolically healthy, weight gain that has been observed in some
patients treated with lanifibranor.
* Treatment with lanifibranor alone and in combination with empagliflozin
decreased the ratio of visceral abdominal fat to subcutaneous fat,
reflecting a shift from pro-inflammatory visceral fat towards metabolically
healthy adipose tissue.
* The treatment with lanifibranor 800mg/once daily alone or in combination
with empagliflozin for 24 weeks was well tolerated, with no safety concerns
reported.
* Inventiva will host an investor webcast Tuesday, March 19(th) at 8am ET
(details below).
Daix (France), Long Island City (New York, United States), March 18, 2024 -
Inventiva (Euronext Paris and Nasdaq: IVA), a clinical-stage biopharmaceutical
company focused on the development of oral small molecule therapies for the
treatment of metabolic dysfunction-associated steatohepatitis (MASH), also known
as non-alcoholic steatohepatitis (NASH), and other diseases with significant
unmet medical needs, today announces positive results of its interim analysis of
the Phase II, Proof-of-Concept clinical trial, LEGEND, evaluating lanifibranor
in combination with empagliflozin in patients with MASH/NASH and poorly
controlled Type 2 Diabetes (T2D).
The LEGEND trial has been designed as a multi-center, randomized, 24-week
treatment, placebo-controlled Phase
II Proof-of-Concept trial to assess the safety and efficacy of lanifibranor in
combination with the SGLT2 inhibitor empagliflozin for the treatment of patients
with non-cirrhotic MASH/NASH and T2D. The trial is double-blind for the placebo
arm and lanifibranor (800mg daily) arm, and open-label for the combination of
lanifibranor (800mg daily) and empagliflozin (10 mg daily) arm. The diagnosis of
non-cirrhotic MASH/NASH was based on historic histology evaluation or a
combination of non-invasive methods including diagnostic methods including
imaging. As planned per protocol, the interim analysis was done once half of the
63 planned randomized patients with MASH completed the 24-week treatment period
or prematurely discontinued from treatment.
The study achieved the primary efficacy endpoint with an absolute reduction in
Hemoglobin A1c (HbA1c) of 1.14% and 1.59% in patients with MASH and T2D treated
with lanifibranor (800mg daily) or in combination with empagliflozin (10mg
daily) at week 24 compared to an increase of 0.26% observed in the placebo arm.
The study also demonstrated a statistically significant reduction in hepatic
steatosis measured by MRI-PDFF(1), in patients treated with lanifibranor alone
and in combination with empagliflozin, -47% and -38% respectively, compared to
placebo (0%). 83% and 67% of patients treated with lanifibranor alone or in
combination with empagliflozin respectively, showed a reduction greater or equal
to 30% of their hepatic fat, compared to 0% in the placebo arm. In addition, the
study demonstrated a statistically significant effect on several secondary and
exploratory endpoints, including liver enzymes (alanine aminotransferase ("ALT")
and aspartate aminotransferase ("AST")), insulin resistance (HOMA-IR), HDL, and
adiponectin (see tables below). Markers of liver inflammation and fibrosis
(corrected T1 relaxation time (cT1) assessed by LiverMultiScan®) were assessed
for the first time with lanifibranor and showed a significant effect with
lanifibranor alone and in combination with empagliflozin.
The study also demonstrated that patients treated with lanifibranor in
combination with empagliflozin maintained a stable weight throughout the 24
weeks study, addressing the moderate, metabolically healthy, weight gain that
can be observed in some patients treated with lanifibranor alone. Furthermore,
these results demonstrated a significant relative reduction in the VAT/SAT ratio
(visceral and subcutaneous adipose tissue) in patients treated with lanifibranor
alone or in combination with empagliflozin, -5% and -17% respectively, compared
to an increase of 11% in patients under placebo. This result reflects a shift
from pro-inflammatory visceral fat towards metabolically healthy adipose tissue.
The treatment with lanifibranor 800mg/daily alone and in combination with
empagliflozin 10mg/daily for 24 weeks appears to be well tolerated, with no
safety concerns reported.
Dr. Michael Cooreman, M.D., Chief Medical Officer of Inventiva: "The results of
the LEGEND study announced today further illustrate the potential of
lanifibranor to address the broad spectrum of the disease biology of MASH and
T2D. These data complement the already published dataset of lanifibranor
demonstrating fibrosis improvement and MASH resolution but also its role as a
potent insulin sensitizer. With roughly 50% of the U.S. population estimated to
have either prediabetes or diabetes, and the well-established correlation
between MASH and T2D, lanifibranor has a unique mechanism of action to
potentially address the medical need of patients with both MASH and T2D. We wish
to thank the patients who participated in the study and the investigators of
LEGEND."
Dr. Onno Holleboom, MD PhD, endocrinologist and associate professor at Amsterdam
UMC, co-principal investigator of the LEGEND Phase II clinical trial: "It is a
big step seeing these positive results of LEGEND demonstrating the impact of
lanifibranor on steatosis, inflammation and fibrosis while stabilizing weight
with empagliflozin in patients with poorly controlled T2D and MASH. The study
was designed as a proof of concept and these results are significant and
strengthen confidence in the potential of lanifibranor to address the specific
metabolic unbalance in patients with T2D while also addressing steatosis and
fibrosis, a hepatic consequence of insulin resistance."
Prof. Michelle Lai, M.D., Ph.D., Beth Israel Deaconess Medical Center and co-
principal investigator of the LEGEND Phase II clinical trial, said: "These
LEGEND results provide valuable insights on the complementary mechanisms of
action of an SGLT2 inhibitor and the panPPAR agonist, lanifibranor. MASH is a
multifaceted disease that we believe will benefit from combination therapies in
order to properly address the full cardiometabolic spectrum of the disease.
These results of LEGEND suggest that lanifibranor in combination with
empagliflozin could be an ideal combination for patients we care for in our
clinic who suffer from T2D and MASH."
Given that the primary endpoint of LEGEND was met, and statistically significant
results were achieved on several key additional markers, the Company has decided
to stop the recruitment as defined per protocol. More details on these results
are expected to be presented in upcoming scientific conferences and submitted
for publication.
Summary HbA1C improvement at Week 24
+---------------------------+--------------------------------------------------+
| | Full Analysis Set(a) (N=30) |
+---------------------------+-------+-----------------+------------------------+
| |Placebo| | Lani 800mg +Empa 10mg |
| | (n=9) |Lani 800mg (n=11)| (n=10) |
+---------------------------+-------+-----------------+------------------------+
|HbA1c (%), LS Mean Absolute| | | |
|Change from Baseline to | | | |
|Week 24 | 0.26 | -1.14* | -1.59** |
+---------------------------+-------+-----------------+------------------------+
| | Completers(b) (N=24) |
+---------------------------+-------+-----------------+------------------------+
| |Placebo| | Lani 800mg +Empa 10mg |
| | (n=5) |Lani 800mg (n=11)| (n=8) |
+---------------------------+-------+-----------------+------------------------+
|Responders with HbA1C level| | | |
|Â