Memorandum

Diabetic Nephropathy Competitive Landscape – December 29, 2021

  • The table below includes an overview of the diabetic nephropathy competitive landscape. It includes all companies we are aware of with diabetic nephropathy candidates in development, though we acknowledge that it may be incomplete. We will continuously update the table as timelines change.

Sponsor

Drug Name

Class

Status

Other Remarks

J&J

Invokana (canagliflozin)

SGLT-2 inhibitor

Approved

Black box amputation warning removed in August 2020; Novel renal indication approved by FDA in September 2019; CREDENCE renal outcomes trial stopped early after IDMC finds significant efficacy, results presented April 2019 and renal indication requested March 2019 (Identifier: NCT02065791)

AZ

Farxiga (dapagliflozin)

SGLT-2 inhibitor

Approved

Approved in EU and Japan for CKD, with or without diabetes, in August 2021; Approved in US for CKD, with or without diabetes, in April 2021; Granted Breakthrough Therapy designation by FDA in October 2020; Positive DAPA-CKD full results presented at ESC 2020; Positive topline results shared in July 2020; DAPA-CKD stopped early due to “overwhelming efficacy” in March 2020; Fast Track designation granted by FDA in August 2019; DAPA-CKD study in patients with CKD with or without diabetes expected to complete November 2020

Bayer

Kerendia (finerenone)

Non-steroidal MRA (mineralocorticoid receptor antagonist)

Approved

Commercial launch ongoing; Approved in US for CKD in T2D in July 2021; Positive FIGARO-DKD full results and FIDELITY pooled analysis presented at ESC 2021, positive topline results shared in May 2021; Submitted to EMA in November 2020; Positive FIDELIO-DKD full results presented at ASN 2020, positive topline results shared in July 2020; FIGARO-DKD and FIDELIO-DKD trials expected to complete in February 2020 and October 2019, respectively

Lilly/BI

Jardiance (empagliflozin)

SGLT-2 inhibitor

Phase 3

Fast Track designation in CKD granted by FDA in March 2020; EMPA-KIDNEY study in patients with CKD with or without diabetes underway, expected to complete in December 2022

Novo Nordisk

semaglutide

GLP-1

Phase 3

FLOW trial launched June 2019 in people with type 2 diabetes and chronic kidney disease, expected completion August 2024

NIH/JDRF/other collaborators

Allopurinol

Xanthine oxidase inhibitor

Phase 3

Marketed for gout; PERL diabetic nephropathy study in type 1 diabetes ongoing; Expected primary completion August 2019, but final completion set for December 31, 2021 (Identifier: NCT02017171), “active, not recruiting” as of December 2021

AZ/FibroGen/Astellas

Roxadustat

2-OG inhibitor

Phase 3 for anemia associated with CKD

CRL issued in August 2021; Received positive CHMP recommendation in June 2021; FibroGen admits to post-hoc altering safety analyses in April 2021; Submitted to FDA by Fibrogen/AZ in December 2019; FDA filing planned for 1H19, pushed back from 2H18; Approved for patients on dialysis in Japan in November 2019, marketed by Astellas; Approved with national coverage in China for anemia in CKD/ESRD in August 2019, marketed by AZ/FibroGen; Met primary endpoint in OLYMPUS and ROCKIES trials

Daiichi Sankyo

Minnebro (esaxerenone)

Oral MR antagonist

Phase 3

No updates in DKD as of December 2021; Positive topline results from phase 3 released November 2019, full results published December 2020; Phase 3 study initiated September 2017, expected to complete March 2021; Phase 2 study completed July 2016 

Lilly

tirzepatide

GLP-1/GIP dual agonist

Phase 2

In Lilly’s December 2021 Investor Community Meeting, management announced the planned initiation of a phase 2 mechanism of action study in CKD (TREASURE-CKD)

Vifor Pharma/ChemoCentryx)

CCX140

CCR2 (chemokine receptor) agonist

Phase 2

CCX140 development discontinued in FSGS (rare kidney disease) in 1Q21, no updates given on CKD; Vifor Pharma and ChemoCentryx expand alliance to including CCX140 in December 2016, Vifor has option to develop and commercialize CCX140 in more prevalent forms of CKD; Positive topline results reported December 2014; company seeking partner before initiating phase 3

AZ

cotadutide

GLP-1/glucagon dual agonist

Phase 2

Phase 2 initiated in patients with CKD and type 2 diabetes in August 2020, expected completion March 2022

AZ

Verinurad

Uric acid reabsorption inhibitor (URAT-1)

Phase 2

Phase 2 in HFpEF initiated in May 2020, expected completion in April 2022; Phase 2 SAPPHIRE combination study with allopurinol in CKD and hyperuricaemia initiated in July 2019; Data from phase 2 with febuxostat shows rapid reduction in albuminuria for patients with CKD and type 2; Phase 2 completed in August 2018

Scohia Pharma/Takeda

Imarikiren/SCO-272 (fka TAK-272)

Direct renin inhibitor

Phase 2

Listed on pipeline, as of December 2021; Positive phase 2 results published in March 2019; Under development at Scohia Pharma since early 2017

Scohia Pharma

SCO-792

Enteropeptidase inhibitor

Phase 2

Japanese phase 2 initiated in June 2020

Goldfinch Bio

GFB-024

Peripherally restricted cannabinoid 1 (CB1) inverse agonist monoclonal antibody

Phase 1 for severe insulin resistant diabetic nephropathy

Phase 1 launched in May 2021

Novo Nordisk/Epigen

EPGN696

Lysophosphatidic acid 1 (LPA1) receptor antagonist

Preclinical

No updates as of December 2021; Novo Nordisk licensed candidate in May 2018

Discontinued Candidates

Sponsor

Drug Name

Class

Status

Other Remarks

Mitsubishi Tanabe Pharma

MT-3995

MR antagonist

Discontinued (Phase 2)

Removed from company pipeline for diabetic nephropathy as of October 2021; Phase 2 in NASH completed in April 2019; Phase 2 results published in September 2020;

Reata/Kyowa Hakko Kirin

Bardoxolone methyl (RTA 402)

Inhibitor of inflammation

Discontinued (Phase 3)

FDA submission in Alport syndrome slated for end of 2020;  Bardoxolone shifted to rare kidney diseases; Reata’s phase 3 BEACON trial terminated in October 2012 due to safety concerns

Vascular Pharma

VPI-2690B

Targets insulin-like growth factor-1 signaling pathway

Discontinued (Phase 2)

No company news since 2019; Phase 2 completed in March 2017, no updates since; Vascular Pharma receives $9 million in Series A to support VPI-2690B in February 2015

Mesoblast

MPC-300-IV

Mesenchymal precursor cells

Discontinued (Phase 2)

CKD indication appears to have been deprioritized; Phase 2 results released in October 2016; Trial completed (Identifier: NCT01843387); Discussing phase 3 design with FDA

Concert Pharmaceuticals

CTP-499

PDE (phosphodiesterase) inhibitor

Discontinued (Phase 2)

Presumably discontinued in CKD; CTP-499 licensed to Processa Pharmaceuticals in March 2018, to be studied in Necrobiosis Lipodica; Did not meet primary endpoint in phase 2 trial, results released in April 2014; Successful end-of-phase 2 meeting in summer 2014; company seeking partner before initiating phase 3

AbbVie

Atrasentan

Endothelin-receptor antagonist

Discontinued (Phase 3)

SONAR study began 2Q13, enrollment complete 3Q17, terminated 1Q18, results presented April 2019 (Identifier: NCT01858532)

Gilead

GS-4997

ASK-1 inhibitor

Discontinued (Phase 2)

Trial ongoing; completion expected August 2016 (Identifier: NCT02177786). Discontinued 3Q16.

Lilly

Baricitinib (LY3009104)

JAK1/JAK2 inhibitor

Discontinued (Phase 2)

Trial completed September 2014 (Identifier: NCT01683409). Discontinued 2Q16.

NephroGenex

Pyridorin

Oxidation inhibitor

Discontinued (Phase 3)

Company filed for bankruptcy 1Q16

Pfizer

PF-00489791

PDE5 inhibitor

Discontinued (Phase 2)

Trial completed August 2013 (Identifier: NCT01200394). Management mentioned “encouraging” phase 2 data during 3Q14 earnings call. Discontinued 1Q16.

Lilly

LY3016859

TGF-alpha/epiregulin monoclonal antibody

Discontinued (Phase 2)

Trial completed September 2015 (Identifier: NCT01774981). Discontinued 4Q15

Lilly

Undisclosed biologic

Anti-VEGF-1 monoclonal antibody

Discontinued (Phase 1)

Discontinued 1Q16.