Desidustat in Anemia due to Non-Dialysis-Dependent Chronic Kidney Disease: A Phase 3 Study (DREAM-ND)

Agrawal, D. P.; Varade, Deepak; Shah, Hardik; Nazar, Alm; Krishnan, Jayakumar Edathedathe; Shukla, Vibha; Ramakrishna, Chinta; Galahitiyawa, Mahel Chinthana Bandara; Mavani, Sidhharth B.; Rajanna, Sunil; Jikki, Petkar; Silva, Shamila De; Ruhela, Vivek; Koradia, Parshottam; Kansagra, Kevinkumar; Kanani, Pooja; Sharma, Nitin; Zala, Kuldipsinh; Parmar, Deven

doi:10.1159/000523961

Cited by 20 publications

(22 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The remaining Phase 3 RCTs in ND-CKD population had an active treatment with ESA as the control arm. These studies testified the non-inferiority of roxadustat [37,38], molidustat [39,40], daprodustat [41], enarodustat [42], vadadustat [43,44] and desidustat [45] in comparison with darbepoetin alfa. Non-inferiority was confirmed independently from the parameter measured during the evaluation period as the primary endpoint (either change from baseline of Hb levels, the between-arm difference of mean Hb level or achieved mean Hb) (Table 1).…”

Section: Trials In Non-dialysis Ckdmentioning

confidence: 98%

“…Only four studies (three with roxadustat and one with desidustat) reported data on HrQoL, by using the Short Form 36 (SF-36) vitality (VT) and physical functioning (PF) sub-scores. These studies disclosed no significant difference from placebo [34,35] nor from darbepoetin alfa [37,45]. However, only the study with desidustat reported an analysis of the increase of the quality-of-life score during treatment, showing similar improvement of SF-36 from baseline with desidustat and darbepoetin alfa [45].…”

Section: Quality Of Lifementioning

confidence: 99%

“…Overall, studies in ND-CKD enrolled 14,178 patients treated with various agents in 13 Phase 3 trials [33][34][35][36][37][38][39][40][41][42][43][44][45]. Of these, seven studies enrolled ESA-naïve patients (n = 5817, 41%) [33-37, 40, 45], two trials only ESA-treated subjects (n = 498, 4%) [38,39] and those remaining evaluated a mixed population (n = 7863, 55%) [40,[42][43][44].…”

Section: Trials In Non-dialysis Ckdmentioning

confidence: 99%

“…Of these, seven studies enrolled ESA-naïve patients (n = 5817, 41%) [33-37, 40, 45], two trials only ESA-treated subjects (n = 498, 4%) [38,39] and those remaining evaluated a mixed population (n = 7863, 55%) [40,[42][43][44]. Efficacy of HIF-PHIs was compared with either placebo (4 trials) [33][34][35][36] or darbepoetin alfa (9 trials) [37][38][39][40][41][42][43][44][45]. Three studies had short duration (9 or 24 weeks, respectively) [36,42,45], 7 trials lasted 52 weeks [33-35, 38-40, 43] and the remaining three were carried out for ≥ 104 weeks [37,41,44].…”

Section: Trials In Non-dialysis Ckdmentioning

confidence: 99%

“…Efficacy of HIF-PHIs was compared with either placebo (4 trials) [33][34][35][36] or darbepoetin alfa (9 trials) [37][38][39][40][41][42][43][44][45]. Three studies had short duration (9 or 24 weeks, respectively) [36,42,45], 7 trials lasted 52 weeks [33-35, 38-40, 43] and the remaining three were carried out for ≥ 104 weeks [37,41,44].…”

Section: Trials In Non-dialysis Ckdmentioning

confidence: 99%

See 4 more Smart Citations

Evolving Strategies in the Treatment of Anaemia in Chronic Kidney Disease: The HIF-Prolyl Hydroxylase Inhibitors

Locatelli

Minutolo²,

Nicola³

et al. 2022

Drugs

View full text Add to dashboard Cite

Chronic kidney disease (CKD) affects approximately 10% of the worldwide population; anaemia is a frequent complication. Inadequate erythropoietin production and absolute or functional iron deficiency are the major causes. Accordingly, the current treatment is based on iron and erythropoiesis stimulating agents (ESAs). Available therapy has dramatically improved the management of anaemia and the quality of life. However, safety concerns were raised over ESA use, especially when aiming to reach near-to-normal haemoglobin levels with high doses. Moreover, many patients show hypo-responsiveness to ESA. Hypoxia-inducible factor (HIF) prolyl hydroxylase domain (PHD) inhibitors (HIF-PHIs) were developed for the oral treatment of anaemia in CKD to overcome these concerns. They simulate the body's exposure to moderate hypoxia, stimulating the production of endogenous erythropoietin. Some molecules are already approved for clinical use in some countries. Data from clinical trials showed non-inferiority in anaemia correction compared to ESA or superiority for placebo. Hypoxia-inducible factor-prolyl hydroxylase domain inhibitors may also have additional advantages in inflamed patients, improving iron utilisation and mobilisation and decreasing LDL-cholesterol. Overall, non-inferiority was also shown in major cardiovascular events, except for one molecule in the non-dialysis population. This was an unexpected finding, considering the lower erythropoietin levels reached using these drugs due to their peculiar mechanism of action. More data and longer follow-ups are necessary to better clarifying safety issues and further investigate the variety of pathways activated by HIF, which could have either positive or negative effects and could differentiate HIF-PHIs from ESAs.

show abstract

Section: Trials In Non-dialysis Ckdmentioning

confidence: 98%

Section: Quality Of Lifementioning

confidence: 99%

Section: Trials In Non-dialysis Ckdmentioning

confidence: 99%

Section: Trials In Non-dialysis Ckdmentioning

confidence: 99%

Section: Trials In Non-dialysis Ckdmentioning

confidence: 99%

See 3 more Smart Citations

Evolving Strategies in the Treatment of Anaemia in Chronic Kidney Disease: The HIF-Prolyl Hydroxylase Inhibitors

Locatelli

Minutolo²,

Nicola³

et al. 2022

Drugs

View full text Add to dashboard Cite

show abstract

A Food‐Effect Study to Evaluate the Oral Bioavailability of Desidustat

Patel¹,

Momin

Kansagra³

et al. 2022

Clinical Pharm in Drug Dev

Self Cite

View full text Add to dashboard Cite

This randomized, single‐treatment, 2‐sequence study evaluated the food effect on oral bioavailability of desidustat. Healthy adult male and female subjects were enrolled and randomly assigned to receive desidustat 50 mg orally in a fasting state in one period and a fed state in the other period. A standardized high‐fat, high‐calorie breakfast was served to assess the food effect. The pharmacokinetic results showed that the time to maximum blood concentration of desidustat was delayed significantly (P < .0001) in the fed state compared to the fasting state. The ingestion of food decreased the maximum blood concentration (Cmax) compared to the fasting state (mean Cmax, 3248 ng/mL in the fed state vs 5496 ng/mL in the fasting state). The geometric mean ratio of fed/fasting for log‐normal (ln) Cmax was 57. The exposure decreased in the fed state compared to the fasting state (mean area under the concentration‐time curve [AUC] over the dosing interval, 25 559 ng • h/mL in the fed state versus 33 705 ng • h/mL in the fasting state; mean AUC from time 0 to infinity [AUC0‐∞], 25,910 ng • h/mL in the fed state vs 34 233 ng • h/mL in the fasting state). The geometric mean ratio of fed/fasting for lnAUC from time 0 to the last quantifiable concentration and ln AUC0‐∞ was 77 and 76, respectively. The 90%CI of fed/fasting ratio of the geometric mean of lnCmax, AUC over the dosing interval, and AUC0‐∞ of desidustat 50 mg did not fall within 80%–125% margin. Therefore, the absence of food effect could not be established. It can be inferred that food has a significant effect on the oral absorption of desidustat. Therefore, food must not be consumed 1 hour before and 2 hours after the oral administration of desidustat.

show abstract

Desidustat: First Approval

Dhillon

2022

Drugs

View full text Add to dashboard Cite

Desidustat (Oxemia™) is an orally bioavailable, small molecule, hypoxia-inducible factor-prolyl hydroxylase (HIF-PH) inhibitor developed by Zydus Cadila for the treatment of anaemia associated with chronic kidney disease (CKD), COVID-2019 infections and chemotherapy induced anaemia. Desidustat inhibits prolyl hydroxylase domain enzymes, resulting in the stabilisation of hypoxia-inducible factor which stimulates erythropoietin production and erythropoiesis. In March 2022, desidustat received its first approval in India for the treatment of anaemia in adults with CKD who are either on dialysis or not on dialysis. Desidustat is in clinical development in China for the treatment of anaemia in patients with CKD, in Mexico for the management of COVID-2019 infections and in the USA for the treatment of chemotherapy induced anaemia. This article summarizes the milestones in the development of desidustat leading to this first approval for anaemia associated with CKD. Supplementary Information The online version contains supplementary material available at 10.1007/s40265-022-01744-w.

show abstract

Desidustat in Anemia due to Non-Dialysis-Dependent Chronic Kidney Disease: A Phase 3 Study (DREAM-ND)

Cited by 20 publications

References 12 publications

Evolving Strategies in the Treatment of Anaemia in Chronic Kidney Disease: The HIF-Prolyl Hydroxylase Inhibitors

Evolving Strategies in the Treatment of Anaemia in Chronic Kidney Disease: The HIF-Prolyl Hydroxylase Inhibitors

A Food‐Effect Study to Evaluate the Oral Bioavailability of Desidustat

Desidustat: First Approval

Contact Info

Product

Resources

About