Big name Korean pharmaceuticals are shifting their focus to a new type of therapy called biobetters which, unlike biosimilars, are deliberately altered versions of existing biologics that improve the original drug in a significant way.
Biobetters are new molecular entities that are superior, not a similar version of the patent-expired original biological drug. Unlike biosimilars (which are almost, but not wholly, interchangeable for the original), biobetters build upon the initial drug’s compounds to tout improvements in the form of increased safety, quicker action, lower dose, or delivery method, among others.
Experts say these drugs will face less regulatory and market regulations, with some estimating they will enjoy more than 10 years of market protection. Because the drug builds upon the original, biobetters most likely have lower research and development costs as well as less stringent patent barricades to development.
Some multinational and domestic pharmaceuticals are now rushing into biobetter development and skipping the biosimilar market, viewing biobetters as improved versions of existing biologics but carrying a less commercial risk of either biologics or biosimilars.
Multinational pharmas such as AstraZeneca, Sanofi, Merck & Co, and Novo Nordisk are expressing interest in developing a biobetter pipeline, with some striking acquisition or technology transfer deals in the process.
Of Korean pharmaceuticals, five are leading the way.
1. GC Pharma emerges as leading biobetter developer
GC Pharma (previously known as Green Cross) is carving out its territory as a leading biobetter developer in Korea, having gained approval for Hunterase, its Hunter syndrome treatment, in the country while carrying out phase 2 studies in the U.S. for a global launch.
The approval for GC Pharma’s Hunterase came on the heels of clinical trials that proved superior efficacy to the original drug – Shire’s Elaprase – regarding increased walking distance and lower urinary GAG excretion, the company said.
The drug gained the orphan drug designation in the U.S. from the FDA in 2013, the company said. Hunter syndrome is a rare disease with an estimated annual market of around 600 billion won, projected to grow to 1 trillion won in the next few years. GC Pharma said that it is preparing for a global launch following successful trials, aiming to take 50 percent global market share, according to Evaluate Pharma.
GC Pharma is also co-developing an anti-HER2 antibody drug candidate called margetuximab with American biotech MacroGenics. Margetuximab, a biobetter of Roche’s breast cancer therapy Herceptin, is currently in phase 3 tests. MacroGenics said that it is looking toward launching the biobetter drug by 2021.
2. Celltrion corners Remicade market with biosimilar and biobetter drugs
Celltrion is making further advances in increasing its market share in the biologic sphere with its copycat and improved versions of Johnson & Johnson’s Remicade, the company said last month.
Celltrion is currently conducting phase 3 trials for a biobetter called RemsimaSC, which seeks to be an improvement over J&J’s Remicade (infliximab). The new drug touts a superior feature over the original in that it can be administered subcutaneously, indicating the drug can be self-injected at home.
The self-injectable method proves superior to the intravenous injections of both the original Remicade and its biosimilar (also developed by Celltrion), which are both administered intravenously, the company said.
Celltrion said it intends to launch the product in the U.S. and Europe around next year if clinical trials are successful. Industry insiders estimate Remicade, which ranks fifth in world revenues, will face increased competition from both Celltrion’s Remicade biosimilar and biobetter if RemsimaSC is launched successfully.
3. Hanmi Pharmaceuticals uses LASPCOVERY for biobetter development
Hanmi Pharmaceutical is using its novel biotechnology platform LAPSCOVERY (Long Acting Protein / Peptide Discovery Platform Technology), which increases the lasting effect of biologic drugs, to develop six bio-based new medicines.
Of biobetters, the product closest to actual launch is its investigational low blood neutrophils treatment, Rolontis. Hanmi inked a deal with U.S.-based biotech Spectrum Pharmaceuticals to develop the drug that builds off Amgen’s Neupogen. The drug, which uses Hanmi’s LAPSCOVERY technology to reduce dosing frequency to once every three weeks, is currently in phase 3 trials.
The Korean pharmaceutical also signed a 5 trillion won ($4.69 billion deal) with Sanofi in 2015, transferring its diabetes biobetter drug, efpeglenatide, to the French pharma. The biobetter will deliver prolonged half-life, increased safety, and fewer injections compared to existing type 2 diabetes treatments, according to Hanmi.
The once-weekly GLP-1 receptor agonist is currently in phase 3 trials, the company said. The trial results are expected to prove Hanmi’s biobetter development capabilities on the global stage, according to industry insiders.
4. Ildong Pharmaceutical partners with TG Therapeutics to develop rituximab biobetter
Ildong Pharma is developing ublituximab, a biobetter of Ritxuan (rituximab) that treats various autoimmune diseases and cancers with American biopharmaceutical TG Therapeutics.
TG Therapeutics entered an exclusive licensing agreement with Ildong in 2012 to develop the novel anti-CD20 antibody in Korea and the U.S. The new drug aims to be an improvement over rituximab, which raked in around 8.5 trillion won in global sales in 2015, according to local reports.
TG Therapeutics said in October that it met with the U.S. FDA about the results of an ongoing phase 3 GENUINE study that evaluates the safety and efficacy of TG-1101 (ublituximab) plus ibrutinib to treat patients with chronic lymphocytic leukemia.
5. HanAll BioPharma targets eye diseases with HL036
HanAll BioPharma, a subsidiary of Daewoong Pharmaceutical focusing on biologic drug discovery and development in the areas of autoimmune diseases and immuno-oncology, is making major investments in biobetter development.
HanAll currently has seven biobetter candidates in its pipeline, which includes investigational drug HL036 used to treat dry eye disease. HL036 is an anti-TNF ophthalmic solution that has been molecularly engineered to enhance tissue penetration efficiency and TNF-neutralizing potency, the company said.
The new drug candidate, comprising an additional tear active ingredient to Allergan’s Restasis, proved safety and drug tolerance in a phase-1 clinical trial at Seoul National University Hospital, the company said.
HanAll said it partnered with U.S.-based Ora Inc. to submit an investigational new drug (IND) application to the FDA last year. The company started phase 2 clinical studies for dry eye disease in the U.S. in November, and aims to complete the test by August, it said.
The Korean pharmaceutical also partnered with Harbour BioMed to develop, manufacture and commercialize its two biologics, including HL036, in Greater China (including Hong Kong, Macau and Taiwan) starting last year, it said.
HanAll added it is developing a new version of HL036 to treat other eye diseases such as diabetic retinopathy and wet age-related macular degeneration.
<© Korea Biomedical Review, All rights reserved.>