On February 15, biogen submitted a new drug for multiple sclerosis, dimethyl fumarate enteric-coated capsules (English trade name: tecfidera) application accepted by cde.
Dimethyl fumarate is a moisture-proof and mildew-proof raw material commonly used in industry, the molecular structure is simple, and the compound itself is not protected by patents. However, tecfidera, a treatment for multiple sclerosis, is protected by a range of patents for therapeutic and medicinal uses.
For the Chinese market, Biogen also laid out a series of patents. Patent for pharmaceutical use cn1182844c and sub-case cn1615839a applied in October 1999 protect pharmaceutical preparations containing dialkyl fumarate for the treatment of autoimmune diseases, and the patent has expired. Patent application of October 2006 cn101304732a claims protection of pharmaceutical compositions containing 40-50% wt fumarate, the application has been dismissed as invalidated. Patent application of January 2010 cn109044985a claims protection for pharmaceutical preparations in the form of dissolution skeleton tablets, which are still under review. In August 2014, fuma pharma (tecfidera original research company) also applied for patent cn109453133a for a pharmaceutical preparation of dissolution skeleton tablets, and further limited the use of multiple sclerosis, which is still under review.
Subsequently, between 2015 and 2016, Biogen applied for a patent for the medicinal use of multiple sclerosis cn107106530a, a patent for extended-release tablets cn107205942a, and a patent cn107920997a for the preparation of dimethyl fumarate granules for the preparation of extended-release formulations, all of which are under review.
Source: Medicine Cube nextpharma
It is worth mentioning that in order to extend the "statutory monopoly" period as much as possible, biogen applied for a set of limited "dose" patent wo2008us01602 for medical use in February 2008, although it did not enter China, its American family of us8399514b was authorized, the patent protects the use of monomethyl fumarate, dimethyl fumarate or a combination thereof to treat multiple sclerosis, while the active ingredient dose is 480 mg / day. Although the scope of the claims of these patents is very narrow, the "precise" protection of tecfidera is not easy to avoid, because if the dose is changed in order to circumvent the patent, it will lead to a significant decrease in efficacy and/or a significant increase in side effects.
On February 5, 2020, the U.S. Patent Reexamination Board (PTAB) conducted a multi-party review of Mylan's challenge patent us8399514b, ruling that Mylan failed to prove that claims 1-20 of the patent were invalid, and finally Biogen maintained the validity of the patent, and tecfidera also extended the term of protection to 2028 through the patent.
Although the drug process development is not complicated, but the domestic varieties of research manufacturers are relatively not many, including biogen there are only 11 (17 acceptance numbers), and as of now only biogen one has been declared for listing, even if other manufacturers have obtained clinical approvals, they have not seen the registration to carry out clinical trials, but the Renfu Pharmaceutical Industry has not seen the declaration to carry out be clinical trials. Perhaps for domestic enterprises, this small molecule with simple structure but strict patent protection wall is really loved and hated.
Source: Medicine Cube Pharmago - China Declaration Library
tecfidera is the third oral multiple sclerosis drug on the market after Fingolimod and Trifluramide, and it is also biogen's number one product at present, with global sales reaching $4.433 billion in 2019, accounting for 31% of biogen's total revenue. Acquired at a fraction of the cost of cash cattle, tecfidera also provided financial support for Biogen to invest heavily in the development of a new alzheimer's disease drug, aducanumab.
Biogen's major drug sales in 2019 (US$ bn)
tecfidera is currently the world's best-selling multiple sclerosis drug, and listing in China can help it broaden the market, but biogen is facing increasing competitive pressure in the global multiple sclerosis market. Mainly because there is a large group of multiple sclerosis patients in Europe and the United States, many large enterprises will take this disease as one of the priority drug development directions, and continuously improve the market threshold from the aspects of drug safety, long-term benefits, and convenience of administration.
Roche's ocrevus (ocrelizumab), a cd20 monoclonal antibody, is the first drug approved to treat both relapsing-remitting multiple sclerosis (RRMS) and primary progressive multiple sclerosis (ppms) ms, and is easy to administer, after completing the initial load administration of 600 mg (administered in 2 weeks), only need to be injected every 6 months. Although it has been on the market for less than 3 years, sales in 2019 were 3.708 billion Swiss francs. The good thing is that Biogen is also a roche partner and enjoys a share of the sales of the ocrevus. However, two other veteran players have made significant progress, the Phase II Proof-of-Concept Study of the Sanofi btk inhibitor SAR442168 for the treatment of multiple sclerosis, which yielded positive results in 2019 or revolutionized the clinical treatment of multiple sclerosis. Novartis' next-generation S1pr regulator, the siponimod, was approved for listing in 2019. As other players join in, the competition in this field will become more lively in the future.