FDA Delays Decisions on Amgen's Lumakras and Intercept's Ocaliva

Key Insights

• The FDA has postponed the decision dates for Amgen's Lumakras supplemental application for metastatic colorectal cancer due to disappointing survival data.
• Intercept Pharmaceuticals' Ocaliva's full approval for primary biliary cholangitis (PBC) also faces delay, pending further FDA review of its supplemental New Drug Application.
• Ocaliva's application was previously met with skepticism from the FDA's Gastrointestinal Drug Advisory Committee, citing concerns over efficacy and safety data.

The FDA has delayed the target action dates for Amgen's Lumakras and Intercept Pharmaceuticals' Ocaliva, both seeking full approval after initial accelerated approvals. The delays stem from concerns over confirmatory data and advisory committee feedback. These decisions impact the treatment landscape for metastatic colorectal cancer and primary biliary cholangitis (PBC), respectively.

Ocaliva's Approval Faces Scrutiny

Intercept Pharmaceuticals is seeking full approval for Ocaliva (obeticholic acid) for the treatment of primary biliary cholangitis (PBC). The original target action date was October 15, but the FDA has extended the review period. Vivek Devaraj, U.S. President at Intercept, stated the company will continue to engage with the FDA during the review process. Ocaliva, an oral farsenoid X receptor agonist, aims to reduce bile acid accumulation in the liver and initially received accelerated approval in 2016.

However, the FDA's Gastrointestinal Drug Advisory Committee recently voted against recommending Ocaliva for full approval, citing insufficient data to support its clinical benefit. Concerns were raised regarding unfavorable trends in liver transplantation and mortality among patients treated with Ocaliva. The FDA's briefing document highlighted that confirmatory data "failed to demonstrate efficacy."

Lumakras Faces Setbacks in Colorectal Cancer

The FDA's delay for Amgen's Lumakras concerns its application for use in metastatic colorectal cancer. This decision follows disappointing survival data from the Phase III CodeBreaK 300 study, which evaluated Lumakras in combination with Vectibix. The combination showed a 17% to 30% reduction in the risk of death compared to the investigator's choice of intervention; however, these estimates did not reach statistical significance.

Lumakras (sotorasib) received accelerated approval in June 2021 for non-small cell lung cancer patients with the KRAS G12C mutation. However, in December 2023, the FDA declined to grant full approval for this indication after a negative advisory committee vote.

These delays highlight the challenges in securing full approval for drugs initially granted accelerated approval, particularly when confirmatory data does not fully support the initial findings.