No approved-drug candidate for hemoglobin c disease is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
RCSB Protein Data Bank · entry 1DXT · 1.7 Å · ligand PROTOPORPHYRIN IX CONTAINING FE (HEM). Experimental structure, not a prediction.
The provided abstracts contain no information about any drug being tested or used in hemoglobin C disease. The 1958 case report describes three patients with homozygous hemoglobin C disease who were diagnostic problems until haemoglobin electrophoresis was performed, but it reports no treatment outcomes, no survival data, and no response rates. The remaining abstracts concern paroxysmal nocturnal hemoglobinuria (PNH), a different disease. In the APPLY-PNH trial, 62 PNH patients with residual anaemia on standard anti-C5 therapy were randomised to oral iptacopan and 35 to continue standard care. Among evaluable patients, 51 of 60 on iptacopan had a haemoglobin increase of at least 2 g/dL from baseline compared with 0 of 35 on standard care, and 42 of 60 on iptacopan reached haemoglobin of 12 g/dL or higher compared with 0 of 35. The adjusted mean haemoglobin change was +3.59 g/dL on iptacopan versus −0.04 g/dL on standard care. No deaths occurred, and no patients discontinued due to adverse events. Headache and diarrhoea were more common with iptacopan.
A separate 2022 study of 15 PNH patients who switched from a C5 inhibitor to pegcetacoplan reported that after an average of 5.6 months on pegcetacoplan, fewer patients reported fatigue, cognitive symptoms, shortness of breath, muscle weakness, and gastrointestinal problems than they had while on C5 inhibitors. Symptom frequency and severity also decreased, with relative reductions in fatigue frequency of 21% and severity of 33%. However, some patients reported new symptoms after switching, though these were described as infrequent and very mild.
A 2025 Canadian drug agency recommendation states that iptacopan (Fabhalta) should be reimbursed for adult PNH patients with persistent anaemia despite an adequate trial of C5 inhibitor treatment, or who have intolerable adverse events from C5 inhibitors, and that its cost should be negotiated so it does not exceed the drug program cost of pegcetacoplan for PNH. A 2012 study of patients undergoing coronary stent placement found that improvement of anaemia (defined as normalisation of haemoglobin at follow-up) was associated with fewer major adverse cardiac and cerebrovascular events compared with sustained anaemia (hazard ratio 3.558), but this study did not involve hemoglobin C disease.
What is missing: no clinical trial has tested iptacopan, pegcetacoplan, or any other complement inhibitor in patients with hemoglobin C disease. The natural history of homozygous hemoglobin C disease is described only in a 1958 case series with no modern treatment data. Funding for a dedicated trial in hemoglobin C disease, appropriate patient stratification, and a trial design that accounts for the mild haemolytic anaemia typical of this condition are all absent.
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Blood · 2022 · 22 citations
Oral Monotherapy with Iptacopan, a Proximal Complement Inhibitor of Factor B, Has Superior Efficacy to Intravenous Terminal Complement Inhibition with Standard of Care Eculizumab or Ravulizumab and Favorable Safety in Patients with Paroxysmal Nocturnal Hemoglobinuria and Residual Anemia: Results from the Randomized, Active-Comparator-Controlled, Open-Label, Multicenter, Phase III Apply-PNH Study
AbstractBackground: Intravenous (IV) anti-C5 monoclonal antibodies (eculizumab [ECU]/ravulizumab [RAV]) are the standard of care (SoC) for treating patients with hemolytic paroxysmal nocturnal hemoglobinuria (PNH). However, up to 60% of patients have clinically meaningful residual anemia with SoC, secondary to C3-mediated extravascular hemolysis. Iptacopan is a first-in-class, oral, selective complement factor B inhibitor that showed promising safety and efficacy in two Phase II trials enrolling anti-C5-treated and -naïve PNH patients. Aim: We report primary efficacy and safety data from the 24-week randomized treatment period of the pivotal, multicenter, Phase III APPLY-PNH trial (NCT04558918; data cut-off: 26 September 2022). Methods: Adult PNH patients with mean hemoglobin (Hb) <10 g/dL on stable SoC therapy (ECU/RAV) for ≥6 months were randomized 8:5 to receive iptacopan monotherapy 200 mg twice daily or to continue their SoC regimen for 24 weeks. Randomization was stratified by prior SoC therapy and red blood cell transfusions (RBCTs) in the preceding 6 months. The two primary endpoints were the proportion of patients with a ≥2 g/dL Hb increase from baseline and the proportion of patients with Hb ≥12 g/dL, each in the absence of RBCTs. Secondary endpoints were transfusion avoidance, changes from baseline in Hb level, Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) score, absolute reticulocyte count (ARC) and lactate dehydrogenase (LDH) level, rates of clinical breakthrough hemolysis (BTH) and major adverse vascular events (MAVEs), and safety. A prespecified testing procedure adjusted for multiplicity; 2-sided P values are reported for significant endpoints only. Results: Of 97 patients, 62 and 35 were randomized to iptacopan and SoC, respectively. Baseline disease characteristics were balanced between arms. The mean age was 51 years and 69.1% of patients were female. RBCTs were received by 57.7% of patients in the 6 months before randomization; 64.9% and 35.1% had received prior ECU and RAV, respectively, for a mean duration of 4 years. Both primary endpoints were achieved with iptacopan monotherapy, showing superiority vs. SoC (Table); 51/60 iptacopan-treated vs. 0/35 SoC-treated patients with evaluable/non-missing data had a ≥2 g/dL Hb increase from baseline and 42/60 vs. 0/35, respectively, achieved Hb ≥12 g/dL (both P<0.0001). Iptacopan monotherapy also showed superiority in transfusion avoidance, changes from baseline in Hb level, FACIT-F scores and ARC, and rate of clinical BTH (Table). Adjusted mean Hb change from baseline (95% confidence interval) was +3.59 (3.32, 3.86) g/dL for iptacopan vs. −0.04 (−0.42, 0.35) g/dL for SoC (difference: +3.63 [3.18, 4.08] g/dL); mean Hb levels (standard deviation) at 24 weeks, irrespective of RBCTs, were 12.6 (1.4) vs. 9.2 (1.4) g/dL, respectively (Figure). At 24 weeks, nearly all patients (60/62) in the iptacopan arm remained RBCT free vs. 14/35 in the SoC arm. There were no deaths and no serious encapsulated bacteria infections. One iptacopan-treated patient had a MAVE (transient ischemic attack; considered unrelated to iptacopan; iptacopan treatment is ongoing). Headache (iptacopan: 16.1% vs. SoC: 2.9%) and diarrhea (14.5% vs. 5.7%) were more commonly reported with iptacopan, whereas infections/infestations (38.7% vs. 48.6%) and BTH events (3.2% vs. 17.1%) were more commonly reported with SoC. Two SoC-treated patients had serious adverse events of hemolysis, compared with no iptacopan-treated patients. No patients discontinued iptacopan or SoC because of adverse events. Conclusions: In this Phase III trial in PNH patients with residual anemia on IV anti-C5 SoC therapy, single-agent, oral iptacopan resulted in a significant majority of patients achieving clinically meaningful Hb increases and Hb ≥12 g/dL, via resolution of extravascular hemolysis and maintenance of intravascular hemolysis control. These hematological benefits were associated with transfusion independence in almost all patients and clinically meaningful improvements in patient-reported fatigue. Iptacopan monotherapy was well tolerated with a favorable safety profile. Single-agent iptacopan may represent a practice-changing, oral, outpatient treatment for PNH patients who have an inadequate response to IV anti-C5 SoC therapy, potentially becoming a preferred treatment option for patients with hemolytic PNH. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal
https://doi.org/10.1182/blood-2022-171469Coronary Artery Disease · 2012 · 17 citations
Improved anemia is associated with favorable long-term clinical outcomes in patients undergoing PCI
AbstractBACKGROUND: Anemia is associated with an increased risk of mortality in patients who underwent percutaneous coronary intervention (PCI) in the bare-metal stent era. However, there have been no data concerning the clinical importance of anemia improvement during the follow-up period after discharge from the hospital during the drug-eluting stent era. METHODS AND RESULTS: To assess anemia, the hemoglobin level was measured at the time of index PCI with drug-eluting stents and at the subsequent outpatient visit between 3 and 12 months later. Improvement of anemia was defined by the normalization of the hemoglobin level at the follow-up laboratory examination. We analyzed 4300 patients who were tested for initial and follow-up hemoglobin levels. We compared major adverse cardiac and cerebrovascular events (MACCE) between the normal group and the anemia group and between the improved anemia group and the sustained anemia group. The median follow-up period was 25.4 months. There was poorer clinical outcome in the anemia group than in the normal group in terms of MACCE (adjusted hazard ratio 1.479, 95% confidence interval 1.025-2.134, P=0.037). Furthermore, the sustained anemia group showed poorer MACCE than did the improved anemia group (hazard ratio 3.558, 95% confidence interval 2.285-5.539, P<0.0001). On the basis of the multivariate Cox hazard regression model and propensity-score matching, the overall findings were consistent between sustained and improved anemia groups. CONCLUSION: The follow-up of hemoglobin level is important, and improvement of anemia is associated with favorable long-term clinical outcomes.
https://doi.org/10.1097/mca.0b013e3283564869Annals of Internal Medicine · 1958 · 3 citations
HOMOZYGOUS HEMOGLOBIN C DISEASE: REPORT OF THREE CASES
AbstractArticle1 July 1958HOMOZYGOUS HEMOGLOBIN C DISEASE: REPORT OF THREE CASESKOUICHI R. TANAKA, M.D., GEORGE O. CLIFFORD, M.D.KOUICHI R. TANAKA, M.D.Search for more papers by this author, GEORGE O. CLIFFORD, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-49-1-30 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptAlthough hemoglobin electrophoresis is being performed in numerous centers throughout the world, patients with homozygous hemoglobin C disease are encountered infrequently.1Hemoglobin C trait has been found to be present in 2 to 3% of American Negroes,2, 3and the incidence of homozygous hemoglobin C disease has been calculated to be one in 6,000 Negroes.1In the course of a study of hemoglobinopathies during the period of 1953 to 1956, three patients with this hemoglobin pattern have been encountered. Each of these patients was a diagnostic problem until hemoglobin electrophoresis was performed, which revealed only the presence of hemoglobin C....Bibliography1. TerryMotulskyRath DWAGCE: Homozygous hemoglobin C: a new hereditary hemolytic disease, New England J. Med. 251: 365, 1954. CrossrefMedlineGoogle Scholar2. Schneider RG: Incidence of hemoglobin C trait in 505 normal Negroes: a family with homozygous hemoglobin C and sickle-cell trait union, J. Lab. and Clin. Med. 44: 133, 1954. MedlineGoogle Scholar3. SmithConley EWCL: Filter paper electrophoresis of human hemoglobins with special reference to the incidence and clinical significance of hemoglobin C, Bull. Johns Hopkins Hosp. 93: 94, 1953. MedlineGoogle Scholar4. SchwartzHartz SOWH: Mediterranean anemia in the Negro. A reevaluation of four patients and their families, Blood 10: 1256, 1955. CrossrefMedlineGoogle Scholar5. SmithConley EWCL: Clinical features of the genetic variants of sickle cell disease, Bull. Johns Hopkins Hosp. 94: 289, 1954. MedlineGoogle Scholar6. RanneyLarsonMcCormack HMDLGH: Some clinical, biochemical and genetic observations on hemoglobin C, J. Clin. Investigation 32: 1277, 1953. CrossrefMedlineGoogle Scholar7. ZuelzerKaplan WWE: Thalassemia-hemoglobin C disease. A new syndrome presumably due to the combination of the genes for thalassemia and hemoglobin C, Blood 9: 1047, 1954. CrossrefMedlineGoogle Scholar8. KaplanZuelzerNeel EWWJV: Further studies on hemoglobin C. II. The hematologic effects of hemoglobin C alone and in combination with sickle cell hemoglobin, Blood 8: 735, 1953. CrossrefMedlineGoogle Scholar9. SingerKrausSingerRubinsteinGoldberg KAPLHMSR: Studies on abnormal hemoglobins. X. A new syndrome: hemoglobin C-thalassemia disease, Blood 9: 1032, 1954. CrossrefMedlineGoogle Scholar10. KorstClatanoffSchilling DRDVRF: External scintillation counting over the liver and spleen after the transfusion of radioactive erythrocytes, Clin. Res. Proc. 3: 195, 1955. Google Scholar11. BeierwaltesJohnsonSolari WHPCAJ: Use of radioisotopes, 1957, W. B. Saunders Co., Philadelphia. Google Scholar12. OrvisHollySmith HHPBNE: Hemoglobin-C disease, Arch. Int. Med. 96: 126, 1955. CrossrefGoogle Scholar13. HartzSchwartz WHSO: Hemoglobin C disease. Report of four cases, Blood 10: 235, 1955. CrossrefMedlineGoogle Scholar14. SpaetAlwayWard TRHG: Homozygous type "c" hemoglobin, Pediatrics 12: 483, 1953. MedlineGoogle Scholar15. Chernoff AI: The human hemoglobins in health and disease, New England J. Med. 253: 322, 365, 416, 1955. CrossrefMedlineGoogle Scholar16. SingerChapmanGoldbergRubinsteinRosenblum KAZSRHMSA: Studies on abnormal hemoglobins. IX. Pure (homozygous) hemoglobin C disease, Blood 9: 1023, 1954. CrossrefMedlineGoogle Scholar17. WhebyThorupLeavell MSOABS: Homozygous hemoglobin C disease in siblings: further comment on intraerythrocytic crystals, Blood 11: 266, 1956. CrossrefMedlineGoogle Scholar18. RansomeLange JWRD: Homozygous hemoglobin C disease in a 79 year old man with gout, Ann. Int. Med. 46: 420 1957. LinkGoogle Scholar19. Hollingsworth JW: Erythrocyte glycolysis in hemolytic disease, J. Lab. and Clin. Med. 45: 920, 1955. MedlineGoogle Scholar20. DiggsKrausMorrisonRudnicki LWAPDBRP: Intraerythrocytic crystals in a white patient with hemoglobin C in the absence of other types of hemoglobin, Blood 9: 1172, 1954. CrossrefMedlineGoogle Scholar21. ThomasMotulskyWalters EDAGDH: Homozygous hemoglobin C disease, Am. J. Med. 18: 832, 1955. CrossrefMedlineGoogle Scholar22. ErlandsonSmithSchulman MCHI: Thalassemia-hemoglobin C disease in white siblings, Pediatrics 17: 740, 1956. MedlineGoogle Scholar23. BrownSpragueKloepfer CLCCHW: A new syndrome: hemoglobin SC thalassemia, with additional observations on hemoglobin C thalassemia, Clin. Res. Proc. 5: 91, 1957. Google Scholar24. KaplanZuelzerNeel EWWJV: A new inherited abnormality of human hemoglobin and its interaction with sickle cell hemoglobin, Blood 6: 1240, 1951. CrossrefMedlineGoogle Scholar25. WeinsteinSpurlingKleinNecheles IMCLHTF: Radioactive sodium chromate for the study of survival of red blood cells. III. The abnormal hemoglobin syndromes, Blood 9: 1155, 1954. CrossrefMedlineGoogle Scholar26. LangeHagen RDPS: Hemoglobin C disease in identical twins, Am. J. M. Sc. 229: 655, 1955. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Detroit, Michigan*Received for publication May 29, 1957.From the Hematology Service, Department of Medicine, Wayne State University College of Medicine, and the City of Detroit Receiving Hospital, Detroit, Michigan.Requests for reprints should be addressed to Kouichi R. Tanaka, M.D., Department of Medicine, University of California Medical Center, Los Angeles 24, California. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byThe influence of hemoglobinopathies on reproductionIneffective erythropoiesis 1 July 1958Volume 49, Issue 1Page: 30-42KeywordsBloodBlood plasmaExcretionGeneticsHematology and oncologyHemoglobinHemoglobinopathiesHemolytic anemiaHospital medicineThalassemia ePublished: 1 December 2008 Issue Published: 1 July 1958 PDF downloadLoading ...
https://doi.org/10.7326/0003-4819-49-1-30Canadian Journal of Health Technologies · 2025 · 0 citations · open access
Iptacopan (Fabhalta)
AbstractCanada’s Drug Agency (CDA-AMC) recommends that Fabhalta be reimbursed by public drug plans for the treatment of adult patients with paroxysmal nocturnal hemoglobinuria (PNH) who have hemolytic anemia, if certain conditions are met. Fabhalta should only be covered to treat adult patients with a diagnosis of PNH who have persistent anemia (lack of red blood cells [RBCs] to carry oxygen), defined as hemoglobin levels less than 10 g/dL (a measure of how much protein is in RBCs that carry oxygen) despite an adequate trial of C5 inhibitor treatment, or who have intolerable adverse events (AEs) from C5 inhibitor treatment. Fabhalta should only be reimbursed if prescribed by or in consultation with a hematologist with experience managing PNH, and should not be used in combination with other complement inhibitors. The cost of Fabhalta should be negotiated so that Fabhalta does not exceed the drug program cost of treatment with pegcetacoplan for the treatment of adult patients with PNH.
https://doi.org/10.51731/cjht.2025.1105Blood · 2022 · 0 citations
Impact of Pegcetacoplan on Paroxysmal Nocturnal Hemoglobinuria Symptoms in Patients Previously Treated with C5-Inhibitors
AbstractBackground Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired hematologic condition associated with significant morbidity, mortality, and impact on health-related quality of life (HRQoL). In the past, the treatment paradigm for PNH consisted of blood transfusions and treatment with complement component C5 inhibitors (C5-is), eculizumab or ravulizumab. Pegcetacoplan was approved in the US and EU in May 2021 and December 2021, respectively, and is the first approved C3 inhibitor (C3-i) for US adults with PNH and EU adults with PNH who remain anemic despite stable C5 inhibitor treatment for ≥3 months. The objective of this study was to characterize the impact of pegcetacoplan on PNH symptom incidence, frequency, and severity in comparison to C5-is in the Voice of the Patient. Methods This mixed-methods study enrolled consenting, adult patients (>21 years old) with PNH in the US for telephone depth interviews. Eligible participants were required to be currently treated with and have at least 3 months of treatment experience with pegcetacoplan. Symptoms were described on a 7-point Likert scale (where 1 is "infrequent" or "very mild" and 7 is "always" or "very severe"). Results Results from 15 patients (8 female and 7 male) are reported here. Enrolled patients had a median age of 40 years (range 24 - 77) and all had received treatment with a C5-i prior to switching to pegcetacoplan. On average, patients had 5.6 months of pegcetacoplan experience following an average of 29.3 months of C5-i experience. The majority of patients (n=14) reported experiencing PNH symptoms while on C5-is, most notably fatigue (n=14), cognitive symptoms (n=12), shortness of breath (n=12), muscle weakness (n=8), and gastrointestinal problems (n=8). In addition to continuing to experience these PNH symptoms, patients described experiencing moderate to high symptom frequency and severity, with fatigue estimated as a 6.0 and 5.5, respectively, on a 7-point Likert scale, cognitive symptoms as a 5.4 and 4.8, shortness of breath as 5.1 and 4.8, muscle weakness as 5.4 and 4.6, and GI symptoms as a 5.3 and 4.9. After switching from C5-is to pegcetacoplan, fewer patients reported experiencing these residual PNH symptoms, including fatigue (n=12 on pegcetacoplan vs n=14 on C5-is), cognitive symptoms (n=11 vs n=12), shortness of breath (n=7 vs n=12), muscle weakness (n=5 vs n=8), and gastrointestinal problems (n=5 vs n=8) (Figure 1). While PNH symptoms persisted on pegcetacoplan, patients reported reduction in symptom frequency and severity, including fatigue (-21% and -33% relative reduction, respectively), cognitive symptoms (-16% and -18% relative reduction), shortness of breath (-30% and -31% relative reduction), muscle weakness (-18% and -14% relative reduction), and gastrointestinal problems (-16% and -14% relative reduction) compared to their experience on C5-is. Select patients, however, reported onset of new symptoms after switching to pegcetacoplan, including shortness of breath (n=1/15) and muscle weakness (n=1/15), though these were reported as infrequent (1.0 and 2.0, respectively) and very mild (1.0 and 1.0, respectively). Patient-reported symptom experience on C5-is and pegcetacoplan is summarized in Figure 2. Conclusions This study revealed that patients continue to experience residual PNH symptoms while on C5-is and describes improvement of patients' symptom management as it relates to incidence, frequency, and severity after switching to pegcetacoplan. Characterizing the real-world experience of PNH patients on therapy is essential to optimizing treatment options and tailoring therapies to the needs of patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal
https://doi.org/10.1182/blood-2022-163778Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
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