The table below includes an overview of the NASH competitive landscape. It includes all companies we are aware of with NASH candidates in phase 2b development and later, and many earlier stage companies as well, although we acknowledge that it may be incomplete, particularly in these earlier development stages.
- Wins: We were especially thrilled by the positive results from Viking’s highly-anticipated phase 2b VOYAGE trial. The compound showed up to 52% reduction from baseline in liver fat content, improvements in cardiovascular biomarkers, and the remarkably clean safety profile. As well, phase 2b results from NGM Bio for FDF19 analog aldafermin showed statistical significance in stage F4 fibrosis – one of the first compounds to do so in an people with the most advanced stages of liver disease.
- Additionally, several smaller companies reported positive phase 2 trial results, including Hepion, Boston Pharmaceuticals, Akero, and Terns Pharmaceuticals.
- On July 17, 2023, Madrigal announced the completion of its NDA submission seeking accelerated approval for resmetirom in NASH.
- Losses: The negative FDA Advisory Committee Meeting for Intercept’s obeticholic acid in May 2023 was a real set-back for the community. Though the committee made very reasonable points with regards to safety, the risk-benefit tradeoffs, and monitoring for side effects, it is disappointing to see the field to accept that it will have to wait longer for the first-approved treatment. In June 2023, the FDA issued a Complete Response Letter to Intercept for OCA in NASH, indicating the NDA cannot be approved in its current state. In response, Intercept has decided to discontinue all investments related to NASH and focus on rare and serious liver disease. At this point, we suspect that Madrigal’s resmetirom is now the front runner for FDA approval for the first approved NASH therapy.
Approved drugs seeking NASH indication (SGLT2/GLP-2/PPAR)
Sponsor |
Drug Name |
Class |
Status |
Other Remarks |
BI/Zealand |
BI456906 |
GLP-1/glucagon dual agonist |
Fast track designation received from the FDA in June 2021; Phase 2 study launched in April 2021; expected completion in January 2023 |
|
CymaBay Therapeutics |
Seladelpar |
PPARδ agonist |
Primary completion date November 2022; Clinical development for PBC resumed in July 2020; NASH on hold, with potential development in combination with partner. |
|
Hanmi |
HM151211 |
GLP-1/GIP/glucagon triple agonist |
FDA Fast Track Designation granted in July 2020; Positive phase 1 data in February 2020 |
|
Inventiva |
IVA337 |
Triple PPAR a/b/g agonist |
Phase 2b safety and efficacy study completed March 2020; positive results announced June 2020. |
|
Inventiva |
Lanifibranor |
PPAR agonist |
Phase 2 investigator-led trial announces positive results in June 2023; Phase 3 NATiV3 trial is currently underway and expected to complete in 2028; Breakthrough designation from FDA in October 2020; Positive phase 2 NATIVE trial results announced in June 2020 |
|
Lilly |
Tirzepatide (LY3298176)
|
GIP/GLP-1 agonist |
SURPASS 3 substudy shows significant improvements in liver fat in April 2022; Study began Nov 2019, results expected 2H2023 |
|
Novo Nordisk |
Semaglutide |
GLP-1 agonist |
Novo Nordisk grants $9.57 million to support phase 2 semaglutide trial; expected to complete in June 2025 |
|
Novo Nordisk |
Semaglutide |
GLP-1 agonist |
Phase 2 semaglutide trial in cirrhotic NASH fails to meet primary endpoint in June 2022; Phase 3 trial initiated in March 2021 and expected to complete in 2029; Fast Track designation granted by FDA in 3Q20; Phase 3 in NASH expected to begin in 2021; Positive phase 2b multiple dose trial completed in 1Q20. |
|
Zydus |
Saroglitazar 4 mg |
TZD |
P4 |
EVIDENCES-XI trial, investigating saroglitazar in people with NAFLD, was announced in June 2023; trial expects to enroll 1500 participants, establishing one of the largest prospective registry of patients with NASH in the world |
Other candidates
Sponsor |
Drug Name |
Class |
Status |
Other Remarks |
89Bio |
BIO89-100 |
Long-acting glycopegylated FGF21 analog |
Full results in September 2023 show that treatment with pegozafermin at doses of 30 mg once weekly and 44 mg every 2 weeks for 24 weeks led to significant improvements, as compared with placebo, in fibrosis without worsening of NASH, published in NEJM; topline results in March 2023 find that 44 mg every-two-weeks dosing conferred placebo-adjusted effect size of 20%, with full results published in NEJM in June 2023; phase 3 development expected to begin “pretty rapidly”; Enrollment for phase 2b ENLIVEN trial complete in August 2022; Positive topline phase 1b/2a results shared in September 2020. Positive preclinical data presented April 2019. |
|
Akero Therapeutics |
efruxifermin (EXR, AKR-001) |
FGF21 analog |
Results from the phase 2b expansion cohort released in June 2023; Topline results from phase 2b study announced in September 2022; Phase 2b study launched in February 2o21 with expected completion in 2027; Phase 2b/3 planned for 1H 2021. Additional positive phase 2a data presented at The Liver Meeting 2020; Positive phase 2a histological results from BALANCED in July 2020 |
|
Axcella |
AXA1125 and AXA1957 |
Endogenous metabolic modulators |
Expected trial completion in fall 2023; Phase 2b trial with AZA1125 initiated in May 2021; Positive phase 2a data for AXA1125 presented at The Liver Meeting 2020; |
|
Can-Fite |
Namodenoson (CF102) |
Adenosine A3 receptor agonist |
Results for trial expected in April 2023; Phase 2b trial initiated in December 2021; Phase 2a trial results shared October 2021; Phase 2a trial results published in 2020 |
|
Cirius |
MSDC-0602K |
Mitochondrial pyruvate carrier modulator/ insulin sensitizer |
Phase 3 trial announced May 2019, expected completion September 2024; Positive phase 2b EMMINENCE trial announced Nov 2019; Significant improvements in metabolic endpoints; Non-significant improvement in liver histopathology. P3 not yet begun. |
|
Galectin Therapeutics |
GR-MD-02 |
Belapectin (polysaccharide polymer that targets extracellular galectins) |
Enrollment for trial completed January 2023; P2b/3 trial began June 2020 with December 2023 completion date. Phase 2 trials in NASH cirrhosis and advanced fibrosis completed October 2017 and September 2016. |
|
Galmed Pharma |
Aramchol |
Oral SCD1 modulator |
Trial recruitment suspended “due to Aramchol Meglumine being formulated” in August 2022; Primary completion date delayed to December 2024; Phase 3/4 study with primary completion date estimated June 2022. Announced ARMOR trial Sep 2019 Phase 2b results announced June 2018. |
|
Genentech |
BFKB8488A |
bispecific FGFR1/Klothoβ antibody |
Trial completed March 2023 – no results posted; As of 1Q23, completion delayed until February 2023; Phase 2 study expected to complete 1H22; Completed recruiting for phase 1b (n = 136) trial Phase 1 study in NASH and type 2 diabetes recruiting, expected to complete June 2019 |
|
Intercept Pharma |
Obeticholic acid |
FXR agonist |
NDA; P3
|
FDA granted CRL to Intercept for OCA for NASH in June 2023, indicating the NDA cannot be approved in its current state; in response, Intercept has decided to discontinue all investments related to NASH and focus on rare and serious liver diseases; FDA Advisory Committee meeting votes against Intercept’s approval in May 2023; FDA accepts the NDA resubmission for the NDA in January 2023; Intercept resubmits NDA to FDA for OCA in NASH in December 2022; OCA fails to meet primary endpoint in phase 3 REVERSE trial for compensated cirrhosis in September 2022; Intercept announces positive topline results of OCA in F2/F3 fibrosis in July 2022; Intercept continues to work on response to CRL, including a new adjudication process of all liver biopsies by a panel of three independent pathologists; FDA issued CRL in June 2020; Company had October 2020 FDA meeting to clarify CRL; expects to refile NDA in 2022. REGNERATE and REVERSE trials in F1-F3 fibrosis/cirrhosis expected to complete September 2025 and August 2021, respectively |
Lipocine |
LPCN 1144 |
Oral prodrug of bioidentical testosterone |
Fast track designation granted in November 2021; Positive results announced following phase 2 trial; Interim phase 2 results announced January 2019 |
|
Madrigal |
MGL-3196 |
THR-β agonist |
NDA completed July 2023; Madrigal announces positive results from phase 3 MAESTRO-NASH trial in December 2022; Phase 3 MAESTRO-NAFLD data shows “significant and clinically relevant reductions in liver fat; interim data from phase 3 MAESTRO-NASH trial expected 3Q22 and ”; Data from phase 3 trial expected January 2022; 52-week Phase 3 trial announced March 2019 with scheduled completion end 2021. Phase 2 results announced May 2018. |
|
NGM Biopharma |
NGM282 |
FGF19 agonist |
NGMBio announces topline results from phase 2b ALPINE 4 trial announced in May 2023; Phase 2 ALPINE 4 in patients with cirrhosis is continuing and expected to complete in August 2022; Phase 2 ALPINE2/3 study did not meet primary endpoint and has been discontinued in NASH patients; Fibrosis effectiveness confirmed in Feb 2020 and Nov 2019. Multiple dose 2b ALPINE results expected 1H2021. Cirrhosis study commencing 2H20. |
|
Poxel |
PXL770 |
AMPK activator |
Trial completed in March 2023; Positive topline results for phase 2b study reported in August 2022; Phase 2 trial completed October 2021; Phase 2a STAMP-NAFLD reported December 2020 with 2b in 2021 planned; raise of €17.7 million to advance of PXL 770 (and 065) in NASH announced in May 2020. |
|
Viking Therapeutics |
VK2809 |
Liver-selective thyroid beta receptor agonist |
Positive phase 2b results announced in May 2023; Enrollment completed in January 2023; VOYAGE trial announced Dec 2019; expected completion December 2022; phase 2 results announced September 2018 |
Combination Studies
Sponsor |
Drug Name |
Class |
Status |
Other Remarks |
Novartis Pharmaceuticals |
Tropifexor + Licogliflozin |
FXR agonist + SGLT1/2 inhibitor |
Phase 2 ELIVATE study expected to complete in 2023; Safety study (LDL elevation) begun May 2020 and est end in March 2021. |
|
Novo Nordisk/Gilead |
Injectable Semaglutide + cilofexor + firsocostat |
GLP-1+ FXR agonist + ACC inhibitor |
Initiation of phase 2b trial in March 2021 with estimated completion date March 2024; Mixed phase 2 results announced in November 2020; Partnership announced in April 2019 |
|
Pfizer |
ervogastat + clesacostat |
DGAT2i+ACC inhibitor |
Received fast track designation from the FDA in May 2022; Phase 2b trial expected to complete in 2024: Phase 2a trial completed in 2020; |
Discontinued Studies
Sponsor |
Drug Name |
Class |
Status |
Other Remarks |
AbbVie |
Cenicriviroc (CVC) |
CCR2/CCR5 inhibitor |
Phase 3 trial terminated due to lack of efficacy in February 2021; AURORA trial in F2-F3 fibrosis, completion expected Oct 2021; Allergan acquired Tobira September 2016; AbbVie acquired Allergan May 2020 |
|
Albireo |
Elobixitat |
Oral ileal bile acid transporter inhibitor |
Discontinued August 2020 |
|
Allergan |
AGN-242266 |
FXR agonist |
Presumed discontinued as of February 2020; Acquired from Akarna Therapeutics September 2016 |
|
Allergan |
Evogliptin |
DPP-4 inhibitor |
Presumbably discontinued following Abbvie’s acquisition of Allergan in 2020; evogliptin no longer in pipeline; Acquired from Tobira Therapeutics September 2016; Phase 1 trial investigating evogliptin in combination with CVC initiated September 2016 |
|
AstraZeneca/Regulus Therapeutics |
AZD4076/RG-125 |
Anti-microRNA (anti-miR103/107 oligonucleotide) |
AZ pulled out of partnership 2Q17; Phase 2 trial initiated 3Q16; Phase 1 trial completed December 2016 |
|
AstraZeneca |
cotadutide (MEDI0382) |
GLP-1/glucagon dual agonist |
Discontinued in 1Q23; Phase 2b/3 PROXYMO-ADV study initiated in July 2022; Phase 2 trial completed in 2Q21; Safety/PD trial initiated in 3Q19. |
|
BMS |
BMS-986036 |
Pegylated FGF21 analog |
Discontinued in November 2021 following disappointing results in phase 2b FALCON study; Two phase 2 studies in F4 (completion expected Oct 2021) and F3 (completion expected December 2021); Phase 2a data presented at EASL 2017 |
|
Enanta Pharma |
EDP-305 |
FXR Agonist |
Discontinued internal development of NASH candidates in October 2021 after interim analysis of phase 2b ARGON-2; Phase 2b to complete in December 2022; Positive phase 2a results announced September 2019; Fast Track designation in January 2017 |
|
Genfit |
Elafibranor (GFT505) |
Dual PPAR alpha/delta agonist |
Program terminated in 2Q20; will continue in PBC; RESOLVE-IT in F1-F3 fibrosis failed phase 3 interim analysis in May 2020 |
|
Gilead |
Simtuzumab |
LOXL2 monoclonal antibody |
Discontinued 3Q16 |
|
Gilead |
Selonsertib (GS-4997) |
ASK-1 inhibitor |
Removed from NASH pipeline in 2Q20; Missed primary endpoint in STELLAR 4 announced 1Q19; STELLAR 3 trial in F3 fibrosis missed endpoint June 2019 |
|
GSK |
GSK3008356 |
DGAT-1 inhibitor |
No longer appears in GSK pipeline as of 1Q23; Added to GSK’s pipeline in 1Q16 |
|
J&J |
JNJ-0795 |
undisclosed |
P1 |
|
Merck (from NGM Bio) |
MK-3655 (formerly NGM313) |
KLB-FGFR1c receptor complex agonist |
Trial terminated in late 2022; Phase 2b study began November 2020, est completion September 2023 ; Merck optioned from NGM Bio in January 2019. |
|
Novartis |
LJN452 (tropifexor) |
FXR agonist |
Phase 2 FLIGHT-FXR study was completed April 2020. |
|
Novartis |
LIK066 |
SGLT-1/SGLT-2 inhibitor |
Presumed discontinued 3Q21; Completed Nov 2019; |
|
Novartis/AbbVie |
Tropifexor + Cenicriviroc |
FXR agonist + CCR2/5 |
Removed from pipeline and presumably discontinued; Study completed 1Q21, results posted on clinicaltrials.gov but not yet published; Phase 2b study expected completion September 2020 |
|
Pfizer |
PF-06667272 |
Myeloperoxidase Inhibitor |
Discontinued 4Q17 |
|
Pfizer |
PF-06835919 |
Ketohexokinase (KHK) inhibitor |
Discontinued in 3Q21; Phase 2 study with metformin in NASH/diabetes patients; |
|
Pfizer |
PF-05221304 |
ACC inhibitor |
Discontinued in October 2020; possible future combination product |
|
Shire |
SHP626 |
Apical sodium bile acid cotransporter inhibitor |
Phase 1 trial completed July 2015 |
Early Phase Studies
Sponsor |
Drug Name |
Class |
Status |
Other Remarks |
Boston Pharmaceuticals |
BOS-580 |
FGF21 |
Positive phase 2a results announced in June 2023 |
|
Terns | TERN-501 |
THR-beta agonist |
Positive phase 2a results announced in August 2023 |
|
Terns |
TERN-101 |
FXR agonist |
Recruitment complete in April 2023; Phase 2a combination study with THR-beta agonist TRN-501 initiated in July 2022; Topline results from phase 2a trial announced in June 2021 showing improvement in liver biomarkers; Closed an $87 million Series C in January 2021; First patient dosed in phase 2a LIFT trial in July 2020; Phase 1 results that confirm safety and efficacy announced February 2020; Fast Track designation in October 2019; Acquired from Lilly in April 2018 |
|
Oramed |
ORMD-0801 |
Oral insulin |
Phase 2a topline results announced in November 2022; no information shared on future development |
|
HighTide Therapeutics |
HTD1801 |
Anti-inflammatories |
Positive topline results from phase 2a study announced in May 2020 |
|
Hepagene |
HPG1860 |
FXR agonist |
Positive results from phase 2a RISE trial announced in January 2023 |
|
Hepion |
rencofilstat |
cyclophilin inhibitor |
Phase 2a results from the ALTITUDE-NASH trial (n=70) announced in May 2023 |
|
Chemomab |
CM-101 |
CCL24-neutralizing monoclonal antibody (MAb) |
Phase 2a topline results announced January 2023 – no information on future trials shared to date |
|
Merck/Hanmi |
Efinopegdutide (formerly JNJ-5111/ HM12525A ) |
GLP-1/glucagon dual agonist |
Results expected at EASL 2023; see outline of trial design here; License agreement with Merck in August 2020 to commercialize in US and outside of Korea; Originally licensed to Janssen in November 2015, but returned development rights in July 2019 following subpar phase 2 results in obesity (with and without diabetes) |
|
NeuroBo Pharmaceuticals |
DA-1241 |
GPCR 119 agonist |
P2a |
Finished dosing of the first patient in September 2023; interim analysis expected in 1H2024, and full data expected in 2H2024. Received first site IRB Approval for phase 2a trial in August 2023; in May 2023, NeuroBo announced that the FDA has cleared the IND submission, with a phase 2 trial expected to begin in 3Q23; Announced FDA IND submission for phase 2 development in April 2023 |
Pfizer |
PF-06865571 |
DGAT2 inhibitor |
As of 1Q23, completion delayed to early 2024; Phase 2 trial expected to complete November 2023; New phase 1 trial launched May 2018, expected to complete February 2019; Prior phase 1 trial completed July 2017; Other phase 1 studies completed and ongoing in subjects with and without NASH |
|
Arrowhead |
ARO-ANG3 |
Angiopoietin-like protein 3 inhibitor |
Phase 2 study estimated completion in December 2024; Phase 1 study completed December 2019; potential treatment for dyslipidemia and other metabolic diseases, including NASH |
|
Altimmune |
Pemvidutide |
GLP-1/glucagon dual agonist |
Phase 2b IMPACT trial initiated in August 2023; Phase 1b topline results announced in December 2022 |
|
Eccogene |
ECC4703 |
THR-beta agnoist |
Phase 1 trial investigating ECC4703 in healthy volunteers; expected completion is July 2023; announced a $25 million Series B raise in June 2023 |
|
Novartis |
IFM-2427 |
NLRP3 inhibitor |
P1 |
Acquired from IFM Tre in April 2019 |
Arrowhead |
ARO-PNPLA3 |
PNPLA3 inhibitor |
Acquired by J&J in 2018; full rights returned to Arrowhead in February 2023 |
|
Lilly |
Undisclosed |
GLP-1/glucagon dual agonist (oxyntomodulin analog) |
P1 |
Announced development for NASH in R&D update in May 2016; Advanced to phase 1 in 4Q16 |
J&J |
JNJ-2463 |
CB1 inverse agonist |
P1 |
Phase 1 study underway according to J&J’s 2017 Pharmaceutical Business Review; Collaboration with BirdRock Bio |
AstraZeneca |
AZ 2693 (formerly IONIS-AZ6-2.5-LRx) |
PNPLA3 inhibitor |
Added to AZ pipeline in 2Q19; Acquired from Ionis in April 2018 |
|
Arrowhead |
ARO-HSD |
RNAi |
Preliminary phase 1 results suggest ARO-HSD was well tolerated and led to improvements in NASH biomarkers. GSK partnered with Arrowhead in $1 billion exclusive licensing agreement for ARO-HSD; Phase 1 study expected to complete in February 2022, topline results presented at The Liver Meeting establish proof-of-concept |
|
Better Therapeutics |
BT-001 |
Prescription cognitive behavioral therapy |
Topline results announced December 2022 |
|
Novartis |
RLX030 |
Relaxin receptor |
Undisclosed |
Data expected to read out in 2019; Also in phase 3 for acute heart failure |
Lynkogen/Alteogen |
Undisclosed |
Long-acting "GLP-1 fusion" combination therapies |
Undisclosed |
Partnership announced July 2018 |
Biostax Corp |
JKB-122 |
long-acting TLR4 antagonist |
N/A |
FDA acceptance of IND in NASH and NAFLD announced in August 2023 |