Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Enpatoran
Enpatoran low dose · 3 trials · 2 indications
The CLASI (Cutaneous Lupus Erythematosus Disease Area and Severity Index) was a validated instrument used to assess disease activity (CLASI-A) and damage in lupus erythematosus. The activity scale included erythema, scale/hypertrophy, active alopecia, recent hair loss, and mucous membrane disease, while the damage scale measured dyspigmentation, atrophy, and scarring. CLASI-A scores ranged from 0 to 70, with mild, moderate, and severe disease corresponding to scores of 0-9, 10-20, and 21-70, respectively. Erythema and scale/hypertrophy sub-scores were computed across 13 body areas, with maximum scores of 39 and 26, respectively. The remaining 5 points reflected contributions from active alopecia (0-3), recent hair loss (0-1), and mucous membrane involvement (0-1), completing the total CLASI-A activity score. Directionality reflected worsening with higher scores and improvement with lower scores.
BILAG-based BICLA response is defined as participants meeting all of the following criteria: 1. Improvement in baseline BILAG scores in all organ systems with moderate or severe disease activity-i.e., all grade A scores (severe disease requiring high-dose therapy) must improve to B (moderate), C (mild), or D (no activity); all grade B scores (moderate disease requiring moderate therapy) must improve to C or D; 2. No new BILAG A scores and no more than one new BILAG B score; 3. No worsening in total SLEDAI-2K score from baseline; 4. No significant deterioration (≤10%) in physician's global assessment; and 5. No treatment failure, defined as initiation of non-protocol therapy. Directionality is toward clinical improvement and disease stabilization.
| Arm | Type | Description |
|---|---|---|
| Cohort A: Placebo | PLACEBO_COMPARATOR | Participants with CLE (active SCLE and/or DLE) or SLE with predominantly active lupus rash (Cutaneous Lupus Erythematosus Disease Area and Severity Index \[CLASI-A\] greater than or equal to \[\>=\] 8) will be enrolled in Cohort A to receive placebo matched to Enpatoran. |
| Cohort A: Enpatoran low dose | EXPERIMENTAL | Participants with CLE (active SCLE and/or DLE) or SLE with predominantly active lupus rash (CLASI-A \>= 8) will be enrolled in Cohort A to receive low dose of Enpatoran. |
| Cohort A: Enpatoran medium dose | EXPERIMENTAL | Participants with CLE (active SCLE and/or DLE) or SLE with predominantly active lupus rash (CLASI-A \>= 8) will be enrolled in Cohort A to receive medium dose of Enpatoran. |
| Cohort A: Enpatoran high dose | EXPERIMENTAL | Participants with CLE (active SCLE and/or DLE) or SLE with predominantly active lupus rash (CLASI-A \>= 8) will be enrolled in Cohort A to receive high dose of Enpatoran. |
| Cohort B (Part 1 + Part 2): Placebo | PLACEBO_COMPARATOR | Participants with active SLE who have moderate to high systemic disease activity (British Isles Lupus Assessment Group \[BILAG A/2B\]) with 1 or 2 of the following: CLASI-A \>= 8 and/or Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) \>= 6 will be enrolled in Cohort B to receive placebo matched to Enpatoran . |
| Cohort B (Part 1 + Part 2): Enpatoran high dose | EXPERIMENTAL | Participants with active SLE who have moderate to high systemic disease activity (BILAG A/2B) with 1 or 2 of the following: CLASI-A \>= 8 and/or SLEDAI \>= 6 will be enrolled in Cohort B to receive high dose of Enpatoran. |
| Cohort B (Part 2): Enpatoran low dose | EXPERIMENTAL | Participants with active SLE who have moderate to high systemic disease activity (BILAG A/2B) with 1 or 2 of the following: CLASI-A \>= 8 and/or SLEDAI \>= 6 will be enrolled in Cohort B to receive low dose of M5049. |
| Cohort B (Part 2): Enpatoran medium dose | EXPERIMENTAL | Participants with active SLE who have moderate to high systemic disease activity (BILAG A/2B) with 1 or 2 of the following: CLASI-A \>= 8 and/or SLEDAI \>= 6 will be enrolled in Cohort B to receive medium dose of Enpatoran. |
| Treatment Sequence 1: A-B-C-D | EXPERIMENTAL | Participants will receive a single oral dose of placebo matched to enpatoran (Treatment A) in treatment period 1, followed by a single oral dose of moxifloxacin tablet (Treatment B) in treatment period 2, followed by a single oral low dose of enpatoran tablet (Treatment C) in treatment period 3, followed by a single oral high dose of enpatoran tablet (Treatment D) in treatment period 4. There will be a washout period of at least 10 days between each treatment period. |
| Treatment Sequence 2: B-D-A-C | EXPERIMENTAL | Participants will receive a single oral dose of moxifloxacin tablet (Treatment B) in treatment period 1, followed by a single oral high dose of enpatoran tablet (Treatment D) in treatment period 2, followed by a single oral dose of placebo matched to enpatoran (Treatment A) in treatment period 3, followed by a single oral low dose of enpatoran tablet (Treatment C) in treatment period 4. There will be a washout period of at least 10 days between each treatment period. |
| Treatment Sequence 3: C-A-D-B | EXPERIMENTAL | Participants will receive a single oral low dose of enpatoran tablet (Treatment C) in treatment period 1, followed by a single oral dose of placebo matched to enpatoran (Treatment A) in treatment period 2, followed by a single oral high dose of enpatoran tablet (Treatment D) in treatment period 3, followed a by single oral of moxifloxacin tablet (Treatment B) in treatment period 4. There will be a washout period of at least 10 days between each treatment period. |
| Treatment Sequence 4: D-C-B-A | EXPERIMENTAL | Participants will receive a single oral high dose of enpatoran tablet (Treatment D) in treatment period 1, followed by a single oral low dose of enpatoran (Treatment C) in treatment period 2, followed by a single oral dose of moxifloxacin tablet (Treatment B) in treatment period 3, followed by a single oral dose of placebo matched to enpatoran (Treatment A) in treatment period 4. There will be a washout period of at least 10 days between each treatment period. |
| Period 1: Enpatoran + [14C]enpatoran microtracer | EXPERIMENTAL | - |
| Period 2: Enpatoran + [14C]enpatoran microdose | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| Enpatoran low dose | DRUG | Participants will receive film-coated tablets of Enpatoran at a low dose orally, twice daily (BID) up to 24 weeks. |
| Enpatoran medium dose | DRUG | Participants will receive film-coated tablets of Enpatoran at a medium dose, orally, BID up to 24 weeks. |
| Enpatoran high dose | DRUG | Participants will receive film-coated tablets of Enpatoran at a high dose, orally, BID up to 24 weeks. |
| Placebo | DRUG | Participants will receive placebo matched to Enpatoran up to 24 weeks. |
| Moxifloxacin | DRUG | Participants will receive a single oral dose of moxifloxacin tablet (Treatment B) in either of treatment period 1, 2, 3 and 4. |
| Enpatoran | DRUG | Participants will receive single oral dose of enpatoran tablet on Day 1 |
| [14C]enpatoran microtracer | DRUG | Participants will receive single oral dose of non-labeled enpatoran solution spiked with microtracer of \[14C\]enpatoran on Day 1 of Period 1. |
| [14C]enpatoran microdose | DRUG | Participants will receive intravenous \[14C\]enpatoran microdose administered at 1.5 hours after the oral dose of enpatoran on Day 1 of Period 2. |
Inclusion Criteria: * Active CLE (SCLE and/or DLE) with a CLE disease area and activity index (CLASI-A) \>= 8 * Active SLE with presence of: CLASI-A \>= 8 and BILAG 2004 1B, C, D (that is \[i.e.\], No BILAG 2004 A and No BILAG 2004 \>= 2B) or BILAG 2004 \>= 1A or 2B and 1 or 2 of the following: Hyb...
Top 20 of 32 competitors
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| Biogen Inc. | BIIB | 5 | PHASE3 | Litifilimab |
| Bristol-Myers Squibb Company | BMY | 7 | PHASE3 | Deucravacitinib |
| Viatris, Inc. | VTRS | 5 | PHASE3 | Cenerimod |
| Novartis AG Sponsored ADR | NVS | 7 | PHASE3 | Ianalumab |
| AstraZeneca PLC | AZN | 21 | PHASE3 | Medi-546 |
| Johnson & Johnson | JNJ | 1 | PHASE3 | Nipocalimab |
| AbbVie, Inc. | ABBV | 2 | PHASE3 | Upadacitinib |
| GSK plc Sponsored ADR | GSK | 3 | PHASE2 | Belimumab |
| Sanofi SA Sponsored ADR | SNY | 2 | PHASE2 | SAR441344 |
| Zenas BioPharma, Inc. | ZBIO | 1 | PHASE2 | Obexelimab |
| Alumis Inc. | ALMS | 1 | PHASE2 | Envudeucitinib |
| Immunovant Inc | IMVT | 1 | PHASE2 | IMVT-1402 |
| Amgen Inc. | AMGN | 1 | PHASE2 | Inebilizumab, Blinatumomab |
| Fate Therapeutics, Inc. | FATE | 2 | PHASE2 | FT819 |
| Eli Lilly and Company | LLY | 1 | PHASE1 | LY4298445 |
| Cartesian Therapeutics, Inc. | RNAC | 2 | PHASE2 | Descartes-08 |
| Merck & Co., Inc. | MRK | 1 | PHASE1 | MK-1045 |
| Gilead Sciences, Inc. | GILD | 1 | PHASE1 | KITE-363, Fludarabine, Cyclophosphamide |
| Artiva Biotherapeutics, Inc. | ARTV | 2 | PHASE1 | AB-101, Cyclophosphamide, Fludarabine, Rituximab, Obinutuzumab |
| Cullinan Therapeutics, Inc. | CGEM | 1 | PHASE1 | CLN-978 |
Enpatoran is an investigational small molecule being studied for systemic lupus erythematosus (SLE) and cutaneous lupus erythematosus (CLE), including cutaneous manifestations of lupus with or without systemic disease. It is also used in early-phase studies involving healthy participants to evaluate drug properties.
Enpatoran is a small molecule immunology therapy in development for lupus. Its specific molecular target has not been disclosed in available clinical trial information. The drug is being evaluated for its effects on immune pathways involved in systemic and cutaneous lupus.
Enpatoran is being developed by Merck KGaA, a German pharmaceutical company. The company is conducting clinical trials of Enpatoran across multiple countries, including the United States, Canada, China, Germany, and Switzerland.
Enpatoran is currently in Phase 3 clinical development. A Phase 3 trial, ELOWEN-2, is recruiting participants with cutaneous manifestations of lupus with or without systemic disease. Earlier Phase 1 and Phase 2 studies have been completed.
Enpatoran has been studied in several clinical trials. The WILLOW study (NCT05162586) was a completed Phase 2 trial in systemic lupus erythematosus. The ELOWEN-2 study (NCT07355218) is a recruiting Phase 3 trial in cutaneous lupus. Phase 1 trials include NCT05110027 and NCT06589726 in healthy participants.
Yes, Enpatoran is also known as M5049. The WILLOW study, a completed Phase 2 trial in systemic lupus erythematosus, used the name M5049 in its title. Both names refer to the same investigational drug being developed by Merck KGaA.