Phase 1 Study Shows Similar PK Between Humira and Proposed Biosimilar M923

Momenta Pharmaceuticals’ M923, a proposed adalimumab (Humira) biosimilar, showed bioequivalent pharmacokinetics (PK) and similar safety and tolerability to both EU- and US-licensed Humira in healthy subjects, according to findings from a phase 1 study published today in Pharmacology Research and Perspectives.

The first-in-human study was a randomized, double-blind, 3-arm, single-dose study conducted in 324 healthy subjects at 3 sites in the United Kingdom. Subjects were randomized to receive a 40 mg subcutaneous injection of either M923 or 1 of the 2 reference products (US- or EU-licensed Humira) and were followed for 71 days. Blood samples were taken pre-dose and at multiple intervals to day 71.

The study’s primary endpoints were maximum observed concentration (C_max), area under the curve (AUC) from time 0 extrapolated to infinity (AUC_0-inf), and AUC from time 0 to 336 hours (AUC_0-336). Secondary endpoints included safety and immunogenicity, which were assessed throughout the study.

The researchers found that the geometric least squares means ratios (GMR) were the following between the M923 and EU-licensed and US-licensed reference arms, respectively:

• C_max: 99.4, 102.6
• AUC_0-inf: 100.9, 104.2
• AUC_0-336: 105, 102.9

The 90% confidence intervals of all GMRs fell within pre-specified confidence bounds of 80% to 125%.

Of the 324 subjects, 164 had any adverse events (AE), with 52, 55, and 57 AEs occurring in the M923, US-licensed reference, and EU-licensed reference arms, respectively. Most AEs (124) were considered mild. The most common adverse events reported were headache, nasopharyngitis, and oropharyngeal pain.

The proportion of confirmed anti-drug antibody responses in the 3 study arms was 78.0%, 73.1%, and 75.7% at day 71 for the M923, US-licensed, and EU-licensed arms, respectively.

The researchers concluded that M923 had similar PK to both US- and EU-licensed references in healthy patients, and that no meaningful differences in safety of immunogenicity were observed. These results, they say, support the initiation of confirmatory and supportive studies for the development of the proposed biosimilar.

The study was funded by Baxalta US Inc, a division of Shire. In 2016, Shire terminated its biosimilar collaboration with Momenta following its merger with Baxalta. Shire was obligated to continue to fund Momenta’s development program for M923 until the agreement’s termination. After providing a formal notice, Shire began a transfer of all ongoing clinical, regulatory, and commercialization activities for the proposed biosimilar.