Boryung loses first trial in Lenvima + Keytruda combo patent dispute

IPTAB dismisses invalidation and scope confirmation claims on lenvatinib + pembrolizumab combination patent

Boryung can continue sales of the generic it launched after overcoming registered patents despite first-instance loss

Risk of patent infringement in endometrial and renal cell carcinoma… will Boryung file an appeal?

Boryung has lost the first trial in a patent dispute over the combination therapy of the liver cancer treatment Lenvima (lenvatinib) and Keytruda (pembrolizumab). Although Boryung had already launched a generic after overcoming listed patents, the latest ruling  has left the company facing marketing risks for key indications. To mitigate this risk, the company must now seek a reversal of the ruling by appealing to the Intellectual Property Court.

According to industry sources on the 29th, the Intellectual Property Trial and Appeal Board recently issued a ruling of partial dismissal and partial rejection in a passive scope confirmation trial filed by Boryung against Eisai Korea and Merck regarding an unlisted patent (No. 10-2662228) related to the Lenvima + Keytruda combination therapy. The IPTAB also dismissed the invalidation trial request for the same patent.

This patent covers the ‘combination of a PD-1 antagonist and a VEGFR/FGFR/RET tyrosine kinase inhibitor for treating cancer.’ Merck and Eisai registered this patent in April 2024. The patent covers the combination therapy of Lenvima and Keytruda for the first-line treatment of advanced endometrial cancer and advanced renal cell carcinoma.

Among Lenvima’s indications - ▲ locally recurrent or metastatic progressive differentiated thyroid cancer, ▲first-line treatment for unresectable hepatocellular carcinoma, ▲combination therapy with pembrolizumab for the treatment of patients with advanced endometrial cancer, ▲combination therapy with pembrolizumab as first-line treatment for advanced renal cell carcinoma - this case is related to the 3rd and 4th indications.

Industry analysis suggests that Boryung has effectively suffered a decisive defeat in the first-instance trial over the Lenvima + Keytruda combination patent. However, the ruling does not block the sale of Boryung’s Lenvima generic, Lenvanib. Previously, Boryung had bypassed or invalidated all four listed patents for Lenvima except the substance patent, and received marketing approval for Lenvanib in February last year. It then secured reimbursement listing in July and launched the product. Currently, Boryung’s Lenvanib is the only Lenvima generic on the market.

However, due to this ruling, Lenvanib can no longer be used to treat advanced endometrial cancer and advanced renal cell carcinoma. This is because if Lenvanib is used for these indications, Boryung could face patent infringement lawsuits from Eisai and Merck.

Eisai has already demonstrated a proactive stance in protecting its patent rights, as evidenced by its filing of an active scope confirmation trial regarding the scope of rights during a dispute over another use patent (10-1470653) against Boryung. Although that case concluded with Eisai voluntarily withdrawing its claim following Boryung’s victory in the invalidation trial, had the invalidation trial yielded the opposite result, it could have served as grounds for a patent infringement lawsuit.

At present, Lenvima’s core market remains thyroid cancer and hepatocellular carcinoma (indications 1 and 2). However, Boryung’s concerns have grown as Lenvima’s focus in the global market is rapidly shifting toward combination therapy with Keytruda for endometrial cancer and renal cell carcinoma.

To resolve this patent risk, Boryung must now decide whether to appeal. Industry observers expect that, given the growing importance of combination therapy in Lenvima’s global revenue mix, Boryung is unlikely to accept the first-instance defeat without a challenge.