Oncology Dominates Japan Approvals, Though Overall Tally Is Lower
Executive Summary
Although it approved fewer new products last fiscal year, Japan granted access to a number of important new therapies, including in oncology and several for the first time worldwide, helped by continuing reforms at its regulatory body.
While the number of new active ingredients approved in Japan dipped last fiscal year, a number of important new therapies, notably in oncology, were granted regulatory clearance by the country's expanding regulatory body.
The Pharmaceuticals and Medical Devices Agency (PMDA) approved 39 new active ingredients (including several diagnostics) in the fiscal year to March 31, 2016, down from 52 in the previous year but nevertheless including a number of products in high-need areas.
In an indication of its advanced independent review capabilities, the regulator also granted a couple of world first approvals during the period. Merck Sharp & Dohme Ltd.'s once-weekly DPP-4 inhibitor Marizev (omarigliptin) was cleared for type 2 diabetes, while Shionogi & Co. Ltd.'s Mulpleta (lusutrombopag), a TPO receptor agonist, was approved for thrombocytopenia associated with chronic liver disease in patients undergoing an elective invasive procedure. (Also see "Japan First To Approve Omarigliptin, Lusutrombopag" - Scrip, 30 Sep, 2015.)
Oncology Dominates
Perhaps not surprisingly given the amount of R&D activity generally in the field across the industry, products for cancer (including one related diagnostic) accounted for 12 of the approvals during the period, making oncology the dominant therapeutic sector.
The major approvals included novel targeted therapies for both melanoma and non-small cell lung cancer, with Bristol-Myers Squibb Co.'s CTLA-4-targeting Yervoy (ipilimumab) and AstraZeneca PLC's Tagrisso (osimertinib) among the new wave of drugs being approved in Japan during the year.
The predominance of oncology also contributed to the 11 products that were approved by the PMDA for orphan indications in the period. While this was down from the 27 in the previous year, it was a reflection of manufacturers' efforts to target smaller patient populations.
Two drugs were also given expedited priority reviews for high-need uses, while US ultra-orphan company Alexion Pharmaceuticals Inc. continued its strategic expansion in Japan by gaining two nods for higher-priced targeted therapies, for hypophosphatasia and lysosomal acid lipase deficiency.
MNCs Account For Majority Of Approvals
Putting lie to any lingering doubts that Japan is still "difficult" to access for non-Japanese companies, foreign multinationals dominated the approvals.
Even excluding any alliance deals under which a Japanese company was the approval holder for a licensed-in drug, a total of 23 new drug approvals (59% of the total) were granted to foreign companies last fiscal year.
The European industry led the pack, with Novartis AG securing approval of four products and Bayer Yakuhin Ltd. three.
New Drug/Diagnostics Approvals In Japan Fiscal 2015 |
|||
Product |
Indication |
Company |
Approval Date |
Acoalan (antithrombin gamma) |
Thrombophilia |
July 3, 2015 |
|
Farydak (panobinostat) |
Relapsed/refractory multiple myeloma (orphan) |
Novartis |
July 3, 2015 |
Ofev (nintedanib) |
Idiopathic pulmonary fibrosis |
July 3, 2015 |
|
Olanedine (olanexidine) |
Skin antisepsis at surgical sites |
July 3, 2015 |
|
Plaquenil (hydroxychloroquine) |
Cutaneous/systemic lupus erythematosus |
July 3, 2015 |
|
Strensiq (asfotase alfa |
Hypophosphatasia (orphan) |
Alexion |
July 3, 2015 |
Trulicity (dulaglutide) |
Type 2 diabetes |
July 3, 2015 |
|
Xiaflex (collagenase) |
Dupuytren's contracture |
July 3, 2015 |
|
Yervoy (ipilimumab) |
Unresectable melanoma (orphan) |
BMS |
July 3, 2015 |
Caprelsa (vandetanib) |
Unresectable medullary thyroid cancer (orphan) |
AstraZeneca |
Sept. 28, 2015 |
Copaxone (glatiramer) |
Multiple sclerosis (orphan) |
Sept. 28, 2015 |
|
Effexor (venlafaxine) |
Depression |
Sept. 28, 2015 |
|
Marizev (omarigliptin) |
Type 2 diabetes |
MSD |
Sept. 28, 2015 |
Miticure (house dust mite antigen) |
House dust mite allergic rhinitis |
Sept. 28, 2015 |
|
Mulpleta (lusutrombopag) |
Thrombocytopenia in chronic liver disease |
Shionogi |
Sept. 28, 2015 |
Octreoscan (indium pentetoreotide) |
Diagnosis of neuroendocrine tumors |
Fujifilm RI Pharma |
Sept. 28, 2015 |
P-Tol (sucroferric oxyhydroxide) |
Hyperphosphatemia in chronic kidney disease patients on dialysis |
Sept. 28, 2015 |
|
Ventavis Inhalation (iloprost) |
Pulmonary arterial hypertension |
Bayer Yakuhin |
Sept. 28, 2015 |
Viekirax (ombitasvir, paritaprevir and ritonavir) |
Chronic hepatitis C, compensated cirrhosis (priority review) |
Sept. 28, 2015 |
|
Yondelis (trabectedin) |
Soft tissue sarcoma (orphan) |
Sept. 28, 2015 |
|
Zebiax (ozenoxacin) |
Superficial skin infections/acne |
Sept. 28, 2015 |
|
Provocholine (methacholine) |
Diagnosis of bronchial airway hyperresponsiveness |
Sanwa Kagaku Kenkyusho Co. Ltd./Santen Pharmaceutical Co. Ltd. |
Jan. 22, 2016 |
Repatha (evolocumab) |
familial/normal hypercholesterolemia in high-risk patients |
Jan. 22, 2016 |
|
Targretin (bexarotene) |
Cutaneous T-cell lymphoma (orphan) |
Jan. 22, 2016 |
|
Vaxem Hib (Haemophilus influenzae type B vaccine) |
Prophylaxis of Haemophilus influenzae type B |
Takeda |
Jan. 22, 2016 |
Adynovate (rurioctocog alfa pegol) |
Factor VIII deficiency |
Mar. 28, 2016 |
|
Fycompa (perampanel) |
Epilepsy (adjunctive use) |
Mar. 28, 2016 |
|
Imbruvica (ibrutinib) |
Relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma |
Mar. 28, 2016 |
|
Kanuma (sebelipase alfa) |
Lysosomal acid lipase deficiency (orphan) |
Alexion |
Mar. 28, 2016 |
Kovaltry (octocog beta) |
Factor VIII deficiency |
Bayer Yakuhin |
Mar. 28, 2016 |
Mekinist (trametinib) |
Unresectable melanoma with BRAF mutation (orphan) |
Novartis |
Mar. 28, 2016 |
Nucala (mepolizumab) |
Intractable bronchial asthma |
Mar. 28, 2016 |
|
Primaquine (primaquine) |
Malaria |
Sanofi |
Mar. 28, 2016 |
Sabril (vigabatrin) |
Infantile spasms (orphan) |
Sanofi |
Mar. 28, 2016 |
Sycrest (asenapine) |
Schizophrenia |
Mar. 28, 2016 |
|
Tafinlar (dabrafenib) |
Unresectable melanoma with BRAF mutation (orphan) |
Novartis |
Mar. 28, 2016 |
Tagrisso (osimertinib) |
Inoperable/recurrent EGFR T790M-positive non-small cell lung cancer |
AstraZeneca |
Mar. 28, 2016 |
Xofigo (radium 223) |
Castration-resistant prostate cancer with bone metastases |
Bayer Yakuhin |
Mar. 28, 2016 |
Zykadia (ceritinib) |
Unresectable advanced/relapsed ALK-positive non-small cell lung cancer |
Novartis |
Mar. 28, 2016 |
Source: PMDA. Approval holders only; licensing agreements not shown. |
Shorter Delays
Product approvals in Japan are followed by a process for the granting of reimbursement under the country's national health insurance scheme, and new products can be commercially launched only once they are listed on the official tariff, which typically follows within a few months of approval.
While this adds to the time before patient access, ahead of this stage the PMDA has been steadily expanding its staff and introducing new systems to steadily bring down average approval review times. PMDA chief executive Tatsuya Kondo noted earlier this year that median approval times had fallen to 304 days in fiscal 2014.
Ongoing increases in review and other staff at the PMDA, pre-filing consultations, and harmonization moves enabling the wider acceptance of foreign data, have had a big impact in this effort. The Tokyo-based agency currently has around 850 staff and is aiming to increase the figure to around 1,000 by March 2019 (Also see "Japan PMDA To Kick Off New Asia Training Center" - Scrip, 17 Mar, 2016.).
Industry groups have applauded the improvements, with the US association Pharmaceutical Research and Manufacturers of America saying that it expects the average lag between US/EU and Japanese approvals to fall to around five months in the 2015-19 period, a fraction of the 42 months seen in 2006-09.
Another factor driving the changes is that the number of approval submissions is expected to more than double to a planned 363 in 2015-19, from 160 in 2006-09, PhRMA noted, with multinationals now routinely including Japanese sites in their international Phase III programs for new drugs. (Also see "Japan’s Crossroads: PhRMA’s Scangos Warns Of Policy Change Fallout" - Scrip, 13 Jun, 2016.)
Although it did not influence the fiscal 2015 figures, the PMDA introduced this April a new "Sakigake" system for the expedited approval of breakthrough therapies, which should help further bring down review and approval times. (Also see "Speedy review for pioneering drugs: understanding Japan's new Sakigake process" - Pink Sheet, 21 Apr, 2015.)
From the editors of PharmAsia News.