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Introduction: Emicizumab is the initial subcutaneously administered bispecific antibody approved as a prophylactic treatment for patients with haemophilia A (PwHA). Aim: This study assessed the economic evaluation of emicizumab treatment for non‐inhibitor severe haemophilia A (HA) patients in India. Methods: A Markov model evaluated the cost‐effectiveness of emicizumab prophylaxis compared to on‐demand therapy (ODT), low‐dose prophylaxis (LDP; 1565 IU/kg/year), intermediate‐dose prophylaxis (IDP; 3915 IU/kg/year) and high‐dose prophylaxis (HDP; 7125 IU/kg/year) for HA patients without factor VIII inhibitors. Inputs from HAVEN‐1 and HAVEN‐3 trials included transition probabilities of different bleeding types. Costs and benefits were discounted at a 3.5% annual rate. Results: In the base‐case analysis, emicizumab was cost‐effective compared to HDP, with an incremental cost‐effectiveness ratio (ICER) per quality‐adjusted life‐years (QALY) of Indian rupees (INR) 27,869. Compared to IDP, ODT and LDP, emicizumab prophylaxis could be considered a cost‐effective option if the paying threshold is >1 per capita gross domestic product (GDP) with ICER/QALY values of INR 264,592, INR 255,876 and INR 305,398, respectively. One‐way sensitivity analysis (OWSA) highlighted emicizumab cost as the parameter with the greatest impact on ICERs. Probabilistic sensitivity analysis (PSA) indicated that emicizumab had a 94.7% and 49.4% probability of being cost‐effective at willingness‐to‐pay (WTP) thresholds of three and two‐times per capita GDP. Conclusion: Emicizumab prophylaxis is cost‐effective compared to HDP and provides value for money compared to ODT, IDP, and LDP for severe non‐inhibitor PwHA in India. Its long‐term humanistic, clinical and economic benefits outweigh alternative options, making it a valuable choice in resource‐constrained settings. [ABSTRACT FROM AUTHOR]

Among six inhibitor positive patients, five (Patient ID 3,4,5,7 and 8) were on standard dose of emicizumab prophylaxis for 2 years before switching over to low dose regimen. All inhibitor positive patients were on episodic treatment with either FEIBA or activated recombinant factor VII (rFVIIa) before they switched to standard dose emicizumab or to low dose emicizumab. One inhibitor positive patient (Patient ID1) and two inhibitor negative patients (Patient ID 2 and 6) were on episodic treatment before starting the low dose emicizumab therapy. [Extracted from the article]

Current SARS-CoV-2 Omicron subvariants impose a heavy burden on global health systems by evading immunity from most developed neutralizing antibodies and vaccines. Here, we identified a nanobody (aSA3) that strongly cross-reacts with the receptor binding domain (RBD) of both SARS-CoV-1 and wild-type (WT) SARS-CoV-2. The dimeric construct of aSA3 (aSA3-Fc) tightly binds and potently neutralizes both SARS-CoV-1 and WT SARS-CoV-2. Based on X-ray crystallography, we engineered a bispecific nanobody dimer (2-3-Fc) by fusing aSA3-Fc to aRBD-2, a previously identified broad-spectrum nanobody targeting an RBD epitope distinct from aSA3. 2-3-Fc exhibits single-digit ng/mL neutralizing potency against all major variants of concerns including BA.5. In hamsters, a single systemic dose of 2-3-Fc at 10 mg/kg conferred substantial efficacy against Omicron infection. More importantly, even at three low doses of 0.5 mg/kg, 2-3-Fc prophylactically administered through the intranasal route drastically reduced viral RNA loads and completely eliminated infectious Omicron particles in the trachea and lungs. Finally, we discovered that 2(Y29G)-3-Fc containing a Y29G substitution in aRBD-2 showed better activity than 2-3-Fc in neutralizing BA.2.75, a recent Omicron subvariant that emerged in India. This study expands the arsenal against SARS-CoV-1, provides potential therapeutic and prophylactic candidates that fully cover major SARS-CoV-2 variants, and may offer a simple preventive approach against Omicron and its subvariants. [ABSTRACT FROM AUTHOR]

Many types of cancers are prevalent in India and worldwide. Monoclonal antibodies (MAbs) are one of the major types of cancer therapeutics, which have included MAbs of hybridoma, chimeric, humanized, or human origin. MAbs are mostly generated currently by direct cloning from B cells. Bispecific antibodies (BAbs), as the name suggests, have two different antigen-binding domains in a single molecule and thus have dual functionality/specificity combined in a single antibody. In addition to the detection of two different antigenic molecules, the dual functionality of BAbs can be utilized to mount T-cell-mediated killing of tumor cells wherein one Fv binds to the tumor-specific antigen and the another recruits T cells to the site of action. Breast cancer and prostate cancer are among the most prevalent cancers in women and men, respectively. Biomarkers such as HER2 and ER/PR are expressed in breast cancer, while overexpression of hepsin and prostate-specific membrane antigen is observed in prostate cancer. Developing BAbs against these biomarkers may be a potent therapeutic option to target breast and prostate cancer, respectively. Therefore, an efficient method using recombinant DNA technology and mammalian cell culture platform is required to generate BAbs against specific diseases as biomarkers as well as for the generation of antibody-based therapeutics.