Japan Keytruda NSCLC Approval Sets Stage For Opdivo Showdown
Executive Summary
Keytruda has been approved in Japan for lung cancer, including first-line use, in a batch of new regulatory clearances that also include the country's first prescription drug for irritable bowel syndrome with constipation.
Merck Sharp & Dohme Ltd.'s (Merck & Co. Inc.) Keytruda (pembrolizumab) has received approval in Japan for the additional major indication of non-small cell lung cancer (NSCLC), and looks likely to reach the market in the first few months of next year after it receives a reimbursement price.
The PD-1-targeting antibody is indicated for PD-L1-positive unresectable advanced/recurrent NSCLC in both the first- and second-line treatment settings, and is administered at 200mg every three weeks. MSD KK will manufacture and market the drug and it will be co-promoted with cancer specialist Taiho Pharmaceutical Co. Ltd.
A companion diagnostic, the PD-L1 IHC22C3 PharmDx kit from Dako North America (part of Agilent Technologies Inc.), was approved in Japan in November, and will be used to identify patients suitable for Keytruda treatment.
Merck said these will include those who have been previously treated and whose tumors have any level of PD-L1 expression, and untreated patients with tumors with high levels of PD-L1 expression (usually defined as a tumor proportion score (TPS) of 50% or higher). Tumors with a TPS of less than 1% are considered to have no PD-L1 expression.
The studies used to support the Japanese approval included KEYNOTE-024 in squamous/non-squamous NSCLC patients who had not received prior systemic chemotherapy for metastatic disease and had high PD-L1 expression with no EGFR or ALK aberrations, and KEYNOTE-010 in patients with 1% or more PD-L1 expression who had progressed following platinum-containing chemotherapy and, if appropriate, targeted therapy for EGFR/ALK aberrations.
Pricing Issues
Keytruda was first approved in Japan this September for the much smaller indication of malignant melanoma, but its reimbursement pricing has been delayed amid pricing renegotiations for its comparator drug Opdivo (nivolumab).
Where available, already launched comparators are used to calculate the prices of subsequent same-class drugs in Japan. But there has been public and political concern in the country over the past six months over sharply rising healthcare costs, due in part to the widely expanded use of new, high-priced drugs for cancer and hepatitis C, including Opdivo in the NSCLC setting.
This has become by far the drug's biggest market, and the Ono Pharmaceutical Co. Ltd./Bristol-Myers Squibb Co. product eventually had its price slashed by 50%, in a move also expected to affect the likely pricing of Keytruda in both its indications. (Also see "Japan Slashes Opdivo Price 50% After Prescriptions Surge" - Pink Sheet, 16 Nov, 2016.)
Opdivo, approved for unresectable, advanced or recurrent NSCLC in Japan around a year ago, does not require PD-L1 testing to determine responder patients. Ono filed a patent infringement suit in Japan against Merck in October, which relates to local PD-1 patents and has yet to be resolved. (Also see "Ono Files Japan Patent Action As Keytruda Nears Market" - Scrip, 26 Oct, 2016.)
First IBS-C Drug
The other notable marketing approval in the batch of new clearances was for Astellas Pharma Inc.'s guanylate cyclase-C receptor agonist Linzess (linaclotide; licensed from Ironwood Pharmaceuticals Inc.), for adults with irritable bowel syndrome with constipation.
The product stands to become the first prescription product for this indication in the country, where the disorder affects around 3% of adults.
The approval was supported by a 500-patient Phase III program in Japan that showed statistically significant benefits over placebo against the primary relief scale and bowel movement endpoints.
The approval triggers a $15m milestone payment to Ironwood under the companies' 2009 licensing agreement, and the US firm will also receive escalating royalties based on sales volumes.
Linzess has already been launched for IBS-C in more than 30 countries and top-line data from an ongoing Japanese Phase III trial in patients with chronic constipation are expected next year.
Japan Marketing Approvals Granted Dec. 19, 2016
Product | Company | Indication |
Cymbalta (duloxetine) | pain associated with osteoarthritis (new indication) | |
Ilaris (canakinumab) | familial Mediterranean fever (FMF), tumor necrosis factor receptor-associated periodic syndrome (TRAPS), and hyperimmunoglobulin D syndrome (HIDS)/mevalonate kinase deficiency (MKD) (new indications) | |
Mozobil (plerixafor) | hematopoietic stem cell mobilizer used with G-CSF | |
Otezla (apremilast) | moderate to severe plaque psoriasis | |
Parsabiv (etelcalcetide) | Ono (licensed from KAI Pharmaceuticals Inc./Amgen Inc. ) | secondary hyperparathyroidism in hemodialysis patients |
Riamet (artemether plus lumefantrine) | Novartis AG | malaria |
Selara (eplerenone) | congestive heart failure | |
Tecfidera (dimethyl fumarate) | relapsing multiple sclerosis | |
Treakisym (bendamustine) | first-line, low-grade non-Hodgkin's lymphoma and mantle cell lymphoma (new indications) | |
Vemlidy (tenofovir alafenamide) | chronic hepatitis B | |
Yazflex (drospirone and ethinyloestradiol) | oral contraceptive |
All new products require the calculation and granting of a reimbursement price before they can be included in Japan's national health insurance tariff, which allows launch. This is usually forthcoming within a few months of approval.
From the editors of PharmAsia News.