On 16 September, Pfizer registered a Phase IIb trial to assess the safety and efficacy of PF-06480605 in adult participants with moderate to severe ulcerative colitis (UC).
Pfizer currently markets three products for inflammatory bowel disease (IBD). Two of the products are biosimilars of Janssen’s Remicade (infliximab), Inflectra and Ixifi, and one is a Janus kinase (JAK) inhibitor, Xeljanz. Currently, Pfizer’s ability to leverage its position in the UC market relies on Xeljanz’s performance as well as its ability to grow revenues for Inflectra in the US. With the introduction of PF-06480605, which will be a first-in-class drug for the treatment of UC, Pfizer could increase its sales in the UC market and become one of the main players in this disease space.
PF-06480605 is an antibody that blocks tumour necrosis factor (TNF), such as cytokine 1A (TL1A)/TNF superfamily member 15 (TNFSF15). TL1A helps to induce pro-inflammatory cytokines including TNF alpha cells from CD4 + CD161 + T cells, whereas these cells are resistant to TNF alpha. In a Phase IIa, multicenter, single-arm, open-label trial, Pfizer evaluated the efficacy, safety, and tolerability of PF-06480605 in patients with moderate to severe UC. The primary endpoint was the number of patients with treatment-emergent adverse events (TEAEs), with serious adverse events (SAEs), and who withdrew due to adverse events (AEs). Out of 50 patients, 16% of patients suffered from TEAEs and 2% of patients withdrew due to AEs.
Insights from key opinion leaders interviewed by GlobalData and clinical studies suggest that anti-TNF-α drug therapy failure is a significant issue affecting 25–30% of patients and creating a substantial unmet need. Pipeline drugs that are in late-stage development have yet to demonstrate sufficiently impressive safety and efficacy data to convince physicians to prescribe them. More data is needed to determine whether PF-06480605 will show an appropriate safety and efficacy profile. However, if this molecule possesses a good efficacy profile similar to other TNF inhibitors while having minimal safety issues, it could threaten the patient share of gold standard drugs in UC, such as Remicade and Abbvie’s Humira (adalimumab). Pfizer has begun to plan a multicenter, randomized, double-blind, dose-ranging, Phase IIb study to evaluate the efficacy, safety, and pharmacokinetics of PF-06480605 in 240 participants. The primary endpoint will assess the proportion of patients achieving clinical remission at Week 14, as defined by a total Mayo score (Disease Activity Index for UC assesses the severity of current UC) of less than 2 with no individual subscore greater than 1.
However, Pfizer has only planned to collect data from 240 patients, which is a small sample size compared to other drugs that are at a similar stage. More participants are required for an appropriate statistical analysis in order to file for approval. Furthermore, PF-06480605 will be tested in patients who have failed or been intolerant to conventional therapies, such as anti-TNF, anti- intergrins, anti-IL-12/IL-23, or JAK inhibitors. In a market that is very overcrowded with treatments, PF-06480605 will prove its versatility by testing in patients who have already used many therapies. If it proves its efficacy, it could be used as a first-line biologic. Pfizer is forecast to generate a total of $455.2m in the market from Xeljanz alone in 2026. With the potential of PF-06480605 competing heavily with other biologics, Pfizer could become a dominant player in the UC market.