Ono Files Japan Patent Action As Keytruda Nears Market
Executive Summary
Hot on the heels of Keytruda's US approval for first-line use in lung cancer, and just ahead of the drug’s first local launch, rival PD-1 player Ono has launched a patent infringement suit in Japan against Merck, adding to similar actions brought elsewhere by its global Opdivo partner BMS.
The legal battles between major players in the immuno-oncology space are heating up following the filing of a legal injunction in Japan by Ono Pharmaceutical Co. Ltd. against Merck & Co. Inc.'s subsidiary MSD KK, claiming infringement of patents in the country relating to an anti-PD-1 antibody.
The action, filed by the mid-size Japanese company in the Tokyo District Court on Oct. 24, follows the Sept. 28 manufacturing and marketing approval in Japan of Merck's same-class drug Keytruda (pembrolizumab), for the initial indication of metastatic melanoma (Also see "Japan Approvals Include Keytruda, First Asia Nod for Iclusig" - Pink Sheet, 29 Sep, 2016.).
The product has yet to be granted a reimbursement price, which enables market launch under Japan’s national health insurance system, but this should happen within the next few months, opening up Ono's blockbuster PD-1 inhibitor Opdivo (nivolumab) to a major direct competitor.
Consistent Stance
The legal case adds to those already brought elsewhere against Merck by Bristol-Myers Squibb Co., Ono's global partner for Opdivo. Ono said in a statement that the Japan action reflects its view of the importance of intellectual property and the need to take immediate measures "against any infringement or action that will be likely to infringe" such rights.
The two local PD-1 patents in question, Nos. 4409430 and 5159730, are owned jointly by Ono and a professor at the Kyoto University Graduate School of Medicine, Dr. Tasuku Honjo. The corresponding US and European patents are licensed to BMS, which already has lawsuits underway in both these jurisdictions.
In the US, BMS and Ono filed suit in the District of Delaware in July 2015 alleging infringement of a specific US patent (No. 9,073,994) granted earlier that month, which claims methods for treating cancer with a PD-1 antibody that have been put into practice through the two companies' commercialization of nivolumab.
The drug was originally co-developed by Ono and Medarex Inc. under a 2005 alliance, with the latter company being acquired by BMS in 2009. Ono subsequently retained rights to the antibody in Japan, South Korea and Taiwan after BMS gained rights in the rest of the world.
Open To Settlement
In all the legal cases so far, including the new suit in Japan, Ono and BMS have said they will not seek judicial decisions for Keytruda sales suspensions if, Ono noted, there is an agreement "to pay an appropriate consideration including royalties or if such an order is made by the court."
Some big numbers are linked to the actions. Merck has just reported global nine-month Keytruda sales of $919m, with around half of these coming from use in metastatic melanoma. BMS is reporting its third quarter figures later this week but its first-half worldwide Opdivo sales totaled $1.54bn.
Ono meanwhile is expecting its Japanese sales of Opdivo to reach JPY126bn ($1.21bn) at reimbursement levels this fiscal year (ending next March 31), boosted significantly by its approval and use in non-small cell lung cancer (NSCLC).
Globally, Opdivo has so far maintained an edge over Keytruda in the second-line NSCLC cancer setting as it does not require PD-L1 biomarker testing to identify responder patients. However, Keytruda was approved by the US FDA on Oct. 24 for the first-line treatment of patients with metastatic NSCLC whose tumors have high (50% or greater) PD-L1 expression with no EGFR or ALK aberrations.
While first-line use of Keytruda in the US will still require testing, the FDA also dropped the PD-L1 threshold in the second-line use from at least 50% to just 1% or more (Also see "It’s Here: Merck’s Keytruda Cleared For First-Line Lung Cancer" - Scrip, 25 Oct, 2016.).
Protecting The Franchise?
Besides what Ono clearly believes are valid technical claims related to its patents, the company may also be looking to protect what has become by far its biggest earner in Japan. Opdivo was first approved in this market (and for the first time worldwide) for melanoma in July 2014.
NSCLC has now become by far Opdivo's biggest indication in the country following an approval for this use last December, and Keytruda is currently awaiting Japanese approval for this indication. Opdivo is also approved for renal cell carcinoma while Keytruda is in Japanese development for a range of other cancer types.
On top of this looming commercial rivalry, Opdivo is coming under increasingly intense government cost scrutiny in Japan over its high price (roughly $7,000 for the 100mg/10mL infusion formulation) and rapidly increasing use, which have been driving up the country’s overall healthcare costs. A one-off reduction to its reimbursement price is now looking increasingly likely (Also see "Japan Drug Cost Concerns Rise To The Top" - Pink Sheet, 25 Oct, 2016.).
From the editors of PharmAsia News.