https://orcid.org/0000-0001-6946-4813
Figures & data
Figure 1. (a) Marketed antibody-based biotherapeutics by year. By June 2022, 111 antibody-based biotherapeutic drug products have been approved by the FDA (shown in orange) and 106 have been approved by the EC (shown in green). 19 total antibody-based biotherapeutic drugs have been approved by India (3), Cuba (2), Russia (4), China (9), and Japan (1), but not by the FDA or EC (shown in gray). The total number of unique marketed antibody-based biotherapeutics as of June 2022 is 136 shown in blue with right y-axis showing growth over time. (b) Molecular formats of marketed antibody-based biotherapeutics. Gray regions represent constant regions. Green regions are variable regions. Red regions are a second variable region in the bispecific therapeutics. The purple circles are examples of where a small molecule drug could attach to an antibody and form antibody-drug conjugates (ADCs).
Table 1. Salient characteristics of 89 marketed antibody-based biotherapeutics sorted by their first FDA† approval date*.
Table 2a. Number of clinical indications for the marketed antibody-based biotherapeutics*.
Table 2b. Targets bound by the marketed antibody-based biotherapeutics*.
Table 3. Number of antibody-based biotherapeutic products available for different regular maintenance dose regimens with respect to routes of administration and therapeutic areas*.
Table 4. Pharmacokinetic data for 89 marketed antibody-based biotherapeutics*.
Table 5. Data collection methods*.
Figure 2. (a) Light chain isotypes of marketed antibody-based biotherapeutics over time. Kappa isotypes are much more common than lambda isotypes. (b) Heavy chain isotypes of marketed antibody-based biotherapeutics over time. IgG1 is the most common heavy isotype, while IgG2 and IgG4 are equally common. (c) Types of marketed antibody-based biotherapeutics over time. Murine and chimeric were common early on, but nearly all approved marketed antibody-based biotherapeutics are now either human or humanized. (d) Heavy chain variable region (VH) percent humanness over time. VH humanness is commonly between 70 and 90%. (e) Light chain variable region (VL) percent humanness over time. VL humanness is commonly between 80 and 90%. (f) Reported percent anti-drug antibodies (% ADAs) over time. In recent years it is much more common to see a reported % ADAs below 5%. (g) Comparison of % Humanness and % ADAs. There is no statistically significant correlation between % Humanness and % ADAs reported for the marketed antibody-based biotherapeutics. (h) % ADAs by antibody type. In general, % ADAs decrease from murine to human, however a direct comparison of % ADAs across the products should be interpreted with caution (see results).
Figure 3. Product information. (a) Product presentation of marketed antibody-based biotherapeutics over time. Current trends show a preference of lyophilized and pre-filled syringe or pen over vial. (b) Route of administration of marketed antibody-based biotherapeutics over time. Intravenous is the most used route of administration, but recently, subcutaneous has seen a similar number of approvals as intravenous. Other routes of administration are intradermal, intramuscular, and intravitreal. (c) Regular maintenance dose frequency for marketed antibody-based biotherapeutics over time. QW stands for once weekly, Q2W stands for once every two weeks, and so on. There are 79 regular dosing regiments. In general, Q2W and Q4W are the most used maintenance dosing regimens.
Figure 4. Pharmacokinetic (PK) data over time. (a) Elimination half-life. This varies for all antibody-based biotherapeutics, but most marketed products are eliminated between 15 and 25 days. (b) Clearance. This varies too, but most antibody-based biotherapeutics have a clearance between 5 and 15 mL/hour. (c) Volume of distribution. Values fall mainly between 3 and 9 liters with values between 3 and 6 liters being the most common. (d) Bioavailability. Recent marketed drugs with a subcutaneous route of administration commonly have 90% or more bioavailability. (e) Clearance versus dosing frequency. In general, a higher clearance should result in more frequent dosing, but the median values do not reflect this. (f) Elimination half-life versus dosing frequency. A trend of longer elimination half-lives enabling less frequent dosing is observed.
Figure 5. Four of the main inactive ingredient categories for marketed antibody-based biotherapeutics over time (see Table S1 for all). (a) Buffers. Histidine is the most common, included in 36 marketed antibody-based biotherapeutic formulations. (b) Stabilizing agents. No stabilizing agents is the most common, but if one is used, sucrose is the most common. (c) Tonicity modifiers. No tonicity modifier is the most common, but if one is used, NaCl is the most common. (d) Surfactants. Polysorbate 80 is included in 52 formulations. (e) Buffering agent usage versus heavy chain isotype. The four most common buffers are seen in all isotypes, but histidine is much more common in IgG1. (f) Stabilizing agent usage. Sucrose is the most common in all isotypes, but trehalose is not used in IgG2 or IgG4 products. (g) Tonicity modifiers. Sodium chloride and no tonicity modifier have similar representation across all isotypes. (h) Surfactant. Polysorbate 20 is paired mostly with IgG1 formulations while polysorbate 80 is paired with IgG2 and IgG4.
Figure 6. API concentration and formulation pH. (a) API concentration over time. The most common API concentration is between 10 and 50 mg/mL, however, API concentrations≥100 mg/mL are becoming more common in recent years. (b) Formulation pH over time. In recent years, drug products are being more frequently formulated under acidic formulations (≤6.0). (c) API concentration and formulation pH comparison. Antibody-based biotherapeutics with high concentration formulations are often formulated in mildly acidic conditions.
