PDUFA Dates Pushed for Sotorasib/Obeticholic Acid in GI Indications

Prescription Drug User Fee Act (PDUFA) dates have been pushed back from the original target action dates set by the FDA for sotorasib (Lumakras) and obeticholic acid (Ocaliva) for patients with metastatic colorectal cancer and primary biliary cholangitis, respectively.¹

In May 2021, the FDA granted accelerated approval to sotorasib for the treatment of patients with KRAS G12C mutated non–small cell lung cancer.² However, in December 2023, a complete response letter was given based on the supplemental new drug application (sNDA) in which full approval of sotorasib was sought.³

In May 2016, accelerated approval was given to obeticholic acid plus ursodeoxycholic acid for patients with primary biliary cholangitis.⁴ An sNDA was submitted for full approval of obeticholic acid in this indication.

For both indications, no new target action date has been set.

“We will continue to engage with the FDA regarding our pending application. We are grateful for the continuous and ongoing support of the [primary biliary cholangitis] community,” Vivek Devaraj, US president and chairman at Intercept, said in a press release on the regulatory update for obeticholic acid.

Data From CodeBreaK 300 Examining Sotorasib Combination

The phase 3 CodeBreaK 300 trial (NCT05198934) assessed sotorasib plus panitumumab (Vectibix) in patients with metastatic colorectal cancer.⁵ Patients were randomly assigned 1:1:1 to receive daily sotorasib at 960 mg plus panitumumab at 6 mg/kg every 2 weeks; 240 mg of daily sotorasib plus 6 mg/kg of panitumumab every 2 weeks; or investigators choice of trifluridine/tipiracil (Lonsurf) or regorafenib (Stivarga).

The median overall survival (OS) was not estimable (NE; 95% CI, 8.6-NE) in the 960 mg sotorasib arm (HR, 0.70; 95% CI, 0.41-1.18; P = .20); 11.9 months (95% CI, 7.5-NE) in the 240 mg sotorasib arm (HR, 0.83; 95% CI, 0.49-1.39; P = .50); and 10.3 months (95% CI, 7.0-NE) in the investigator’s choice arm.

Investigators noted that after a median follow-up of 13.6 months, the 960 mg and 240 mg arms showed a trend toward improved OS. Additionally, in the 960 mg arm, there was a 30% reduction in the risk of death.

In the 960 mg sotorasib arm, the objective response rate (ORR) was 30% (95% CI, 18.3%-44.3%), the duration of response (DOR) was 10.1 months, and the median progression-free survival (PFS) by blinded independent central review (BICR) was 5.8 months (95% CI, 4.2-7.5; HR, 0.46; 95% CI, 0.29-0.72).

In the 240 mg sotorasib arm, the ORR was 8% (95% CI, 2.1%-18.2%), the DOR was not reached, and the median PFS by BICR was 4.0 months (95% CI, 3.7-5.9; HR, 0.57; 95% CI, 0.37-0.88).

For the investigator’s choice arm, the ORR was 2% (95% CI, 0%-9.9%), the DOR was not reached (95% CI, 5.2-5.2), and the median PFS was 2.0 months (95% CI, 1.9-3.9).

Obeticholic Acid Data

Currently, obeticholic acid is indicated for use in patients with primary biliary cholangitis without cirrhosis or with compensated cirrhosis who do not have evidence of portal hypertension.⁶ Obeticholic acid can be used in combination with ursodeoxycholic acid for patients who have an inadequate response to ursodeoxycholic acid monotherapy.

Important safety information includes having hepatic decompensation and failure that could result in liver transplant; obeticholic acid is contraindicated in patients who have decompensated cirrhosis a prior decompensation event or have portal hypertension. Patients should permanently discontinue obeticholic acid if they develop a laboratory abnormality or have clinical evidence of portal hypertension.

Severe pruritus was observed in 23% of patients who received obeticholic acid at 10 mg, and 19% of patients experienced severe pruritus in the obeticholic acid titration arm compared with 7% in the placebo arm across a 12-month randomized trial of 216 patients.

References

1. FDA pushes back PDUFA dates for Amgen and Intercept. News release. October 18, 2024. Accessed October 21, 2024. https://shorturl.at/VshwH
2. FDA grants accelerated approval to sotorasib for KRAS G12C mutated NSCLC. News release. FDA. May 28, 2021. Accessed October 21, 2024. https://shorturl.at/Q6bol
3. Amgen provides regulatory update on status of Lumakras (Sotorasib). News release. Amgen. December 23, 2023. Accessed October 21, 2024. https://shorturl.at/7rHfw
4. FDA approves Ocaliva for rare, chronic liver disease. News release. FDA. May 31, 2016. Accessed October 21, 2024. https://shorturl.at/jLkiZ
5. Fakih M, Salvatore L, Esaki T, et al. Overall survival (OS) of phase 3 CodeBreaK 300 study of sotorasib plus panitumumab (soto+pani) versus investigator’s choice of therapy for KRAS G12C-mutated metastatic colorectal cancer (mCRC). 2024;42(17):LBA3510. doi.10.1200/JCO.2024.42.17_suppl.LBA3510
6. Intercept provides regulatory update regarding sNDA for OCALIVA. News release. Intercept. October 17, 2024. Accessed October 21, 2024. https://tinyurl.com/tsze223z