First generics in Japan for tacrolimus, pramipexole, tegafur
This article was originally published in Scrip
The latest regular price listing of generics in Japan includes the first such competition for five active ingredients, including key products for Astellas, Boehringer Ingelheim and Taiho.
In all, a landmark 715 presentations from 85 companies were included in the reimbursement tariff on 21 June, the highest number since the current system of twice-a-year generic listings was adopted in 2008.
The number reflects attractive sales opportunities for some of the products newly opened up to direct competition and moves by the government in recent years to encourage uptake of generics through measures including fee reforms and prescription form changes.
Among the original products affected by first-time generics in the new listing is Daiichi Sankyo/Lead Chemical's transdermal NSAID Loxonin (loxoprofen), which is used in a wide variety of anti-inflammatory indications. The gel and transdermal tape formulations of the drug attracted 62 generic preparations.
Daiichi Sankyo reported Japanese Loxonin sales (all formulations) of JPY59.6 billion ($607 million) in the fiscal year ended 31 March, making it the firm's number two product domestically.
Daiichi Sankyo's calcium antagonist Calblock (azelnidipine) is also facing its first generics, although the sales at risk here are modest at JPY10.9 billion for the original last fiscal year.
But with sales of JPY49.4 billion over the same period (including in once-daily form), the immunosuppressant Prograf (tacrolimus) is Astellas's number three product in Japan, although initial generic competition for the capsule formulation is limited at just three entrants.
Prograf lost exclusivity in its largest single market, the US, back in April 2008, and generic competition there was also relatively slow to take off on concerns over bioequivalence in transplant patients stemming from the molecule's narrow therapeutic window.
As well as use after various organ transplants (for which the still-protected once-daily form, Graceptor, is also marketed), Prograf is approved in Japan for rheumatoid arthritis, lupus nephritis, ulcerative colitis and myasthenia gravis, and most recently for interstitial pneumonia associated with polymyositis and dermatomyositis.
The other two products losing exclusivity are Boehringer Ingelheim's BI-Sifrol (pramipexole), indicated for Parkinson's disease and restless legs syndrome, and Taiho Pharmaceutical's anticancer TS-1 (tegafur, gimeracil and oteracil potassium).
BI-Sifrol is one of Boehringer Ingelheim's mainstay products in Japan and the last sales disclosed by the firm's local subsidiary were JPY13.4 billion in calendar 2009, putting it in the number two spot for the private German group's pharma business.
Among those launching generic versions was Daiichi Sankyo's Espha subsidiary, marking continued moves by many of Japan's leading branded firms to partake in the country's steadily growing generic sector.
TS-1 is the mainstay product at Taiho (a subsidiary of Otsuka Holdings) and is approved for a wide range of malignancies including non-small cell lung, colorectal and breast cancer in addition to its mainstay use of gastric cancer, for which it is a standard therapy in Japan. Global sales of the drug last fiscal year were JPY37.0 billion (the firm does not break out Japanese sales), and Sawai is among the new generic entrants.
Apparently in part to address the generic threat, Taiho will launch next week in Japan a new oral disintegrating formulation that can be taken without water, which it claims is the first such preparation of an anticancer.
New generics are usually priced at 70% of the current reimbursement level of the original drug, although under new rules adopted in April last year, six active ingredients were priced at the 60% level. This applies to molecules for which 10 or more generic versions (any formulation) are listed at one time.
One active ingredient received a price of 90% of the original, under a rule that sets the level at 90% that of the cheapest available generic when large numbers of additional generics (at least 10 oral, or at least 20 injectable or topical formulations) are listed.
Sanofi's anti-allergic Allegra (fexofenadine), which first went generic in Japan last December, attracted a further 47 preparations this time.