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- 2026-05-15 08:49:29
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- Venture capital investment on bio sector breaks record again
- by Kim, Jin-Gu Dec 16, 2019 10:55pm
- The new investment volume in pharmaceutical and bio industry is expected to mark the highest figure in the history, despite multiple risks occurred in the year. Following last year’s record-breaking volume, this year’s investment volume is to break the last year’s record. Korean Venture Capital Association (KVCA) recently published a Venture Capital Market Brief, as of October 2019. The report found the accumulated new investment volume all across industries reached 3.52 trillion won until the October. Apparently, pharmaceutical, bio and medical sector marked the highest ratio of the entire volume. The sector received investment of 984.1 billion won as of October, taking up about 27.9 percent of the total accumulated investment volume. Last year alone, the sector’s investment volume surpassed 841.7 billion won. Following after the top invested sector, the ICT service sector was invested with 782.5 billion won (22.2 percent) showing a gap of 200 billion won with the top sector. Based on the trend, the pharmaceutical, bio and medical sector’s new investment volume in the year is expected to exceed one trillion won for the first time in the history. After placing itself on the top spot last year, the pharmaceutical, bio and medical sector’s new investment volume has been widening the gap between the second place. The sector actually outperformed itself despite a series of fallouts in the year, like revoked approval on Kolon Life Science’ Invossa-K, and failed Phase 3 trials by SillaJen, Helixmith and HLB. KVCA reported 17 out of 21 special technology listing cases were from the pharmaceutical, bio and medical sector. 11 companies from the sector either have already been listed or are to be listed until the end of the year. The association official explained the background of skewed new investment volume and said “Ever since the special technology listing system was implemented from 2005, the pharmaceutical, bio and medical industry’s share of the overall special technology listing has been the biggest at 78.6 percent”.
- Company
- Huons, challenges localization of Hyaluronidase
- by Lee, Seok-Jun Dec 16, 2019 10:55pm
- Huons Group will challenge the global hyaluronidase market worth ₩3 trillion. HuonsLab, a bio research and development company specializing in Huons Group, announced on 16th that it has signed a commissioned research agreement contract with Panzen, a cell line development company, to develop ‘human gene recombinant hyaluronidase’ cell line development and production process development. Panzen, founded in 1999 is engaged in research and development of biopharmaceutical products at home and abroad, including recombinant cell lines and process development. This year, Korea's own biosimilar anemia treatment (EPO) 'Panpotin' was approved in Korea. Hyaluronidase is a recombinant enzyme protein that breaks down hyaluronic acid and is used as a drug diffusion agent. Hyaluronidase has been recently developed to increase the use of Hyaluronic acid fillers for cosmetic purposes, and to increase drug delivery ability in accordance with the trend of developing antibody treatment or protein drugs subcutaneously rather than intravenously. According to GosReports, the global market for hyaluronidase is estimated to be ₩2.70 trillion by 2020. Huon's Lab challenges the localization of human genetic recombinant hyaluronidase. Huon’s Lab plans to establish a development system from the development of human gene recombinant hyaluronidase cell line with Panzen, which has the know-how and technology for the development of recombinant protein-producing cell line and process development. “We are expanding our bio business at the group level to lead the global healthcare market” said Wan-seop Kim, Huon's CEO. "Recombinant human hyaluronidase is an important technology that can be used in various therapeutics. If successful, it can be competitive in the global biologics technology market.".
- Company
- Collapse of Cialis, 6th place in 4 years
- by An, Kyung-Jin Dec 16, 2019 06:21am
- (Clockwise from top left) Photographs of Cendom, Viagra, Palpal, Cialis The market position of Cialis, which squeezed the market for erectile dysfunction with Viagra, was greatly reduced. In the aftermath of the generic drug market by domestic pharmaceutical companies, sales shrank to one-third of patent expiration. The share rank has changed from 1st to 6th place four years ago. Generic products such as 'Palpal' and 'Cendom' continued to strengthen in the entire erectile dysfunction treatment market. According to IQVIA data on the 11th, the market for erectile dysfunction drugs in the third quarter was ￦28.3 billion, an increase of 8.3% compared to the previous year. This is an increase of 13.8% from ￦25.3 billion in the third quarter 2015. Quarterly market size is steadily rising as generic products launched by domestic pharmaceutical companies are growing. Quarterly Sales of Major Erectile Dysfunction Therapeutics (Unit: KRW million, Source: IQVIA) In terms of sales of erectile dysfunction treatment, Hanmi Pharmaceutical's 'Palpal' has firmly maintained its leading position for four years since 2016. Palpal is a generic product of Viagra (Sildenafil) released in 2012. Palpal sold ￦5.7 billion in the third quarter, accounting for 20.1% of the market for erectile dysfunction. The company's sales grew 10.6% YoY to ￦5.2 billion, maintaining a more than double gap with its second-place Cendom. Palpal, which made an entry mark in the erectile dysfunction treatment market immediately after its patent expiration, exceeded sales of Viagra, the same ingredient as its original product, within a year after its release. In the fourth quarter of 2015, even the original Cialis, which was Tadalafil-based, beat the original erectile dysfunction treatment throne. Since then, it has not missed a market leader. Strong accent for generics were even more pronounced in the Tadalafil market. Chong Kun Dang's 'Cendom' remained second in sales, selling ￦2.5 billion in the third quarter. The company's market share increased to 8.8%, recording a 6.3% year-on-year growth. Cendom is a generic product that was released after the Cialis (Tadalafil) patent expired in September 2015. Since its launch, its market share has gradually increased, surpassing the original Cialis in the fourth quarter of 2017. In the fourth quarter of last year, the company is chasing Palpal by exceeding Viagra sales. Gugu by Hanmi, Another generic product of Tadalafil, ranked fourth overall in the third quarter, selling ￦1.8 billion, a 6.3% increase from the previous year. Original pharmaceuticals from multinational pharmaceuticals showed a sharp decline. Cialis sales in Lilly Korea fell 13.6% YoY to ￦1.5 billion. Compared to ￦5.1 billion in the third quarter of 2015, two-thirds of sales evaporated. At the same time as Cialis expired, it gave Palpal by Hanmi Pharmaceuticals a leading position in sales of erectile dysfunction drugs in Korea. Since then, The sales have been sequentially overtaken by Pfizer Viagra and Chong Kun Dang Cendom. Lilly signed a contract with Handok, a former sales partner, last year Lilly took complete charge of Cialis' domestic distribution, marketing and sales activities. However, there was no sales rebound effect. Cialis was pushed down to the same ingredient generic product, Gugu, in the second quarter of this year, and was lower than SK Chemical's 'MvixS' (Mirodenafil). After four years of patent expiry, the sales ranking has fallen by five steps. The gap with Dong-A 'Zydena (Udenafil), which ranked seventh in the third quarters, is only ￦10 million. Pfizer's Viagra sales are unlikely to recover. Viagra's third quarter sales came in at ￦2.4 billion, similar to the same period last year. The domestic market for erectile dysfunction drugs is estimated at 8.4%. It was once called the pronoun for erectile dysfunction, but its current sales are less than half of its Palpal. Comparison of 2018-2019 3Q revenue of major erectile dysfunction treatments (Unit:￦1million, %, Source: IQVIA)
- Company
- Industry feels growing pressure on metformin risk
- by Chon, Seung-Hyun Dec 16, 2019 06:21am
- Ministry of Food and Drug Safety (MFDS) The pharmaceutical industry’s concern over metformin impurity contamination is growing. The industry’s eyes are focused on the government’s action following its ongoing metformin usage status review. Some of pharmaceutical companies are promptly equipping themselves with impurity analyzer a self-testing. ◆MFDS initiates metformin usage status review, the industry fears of follow-up action An industry source reported on Dec. 15 that Korea’s Ministry of Food and Drug Safety (MFDS) has ordered pharmaceutical companies to assess manufacturing record of pharmaceutical product containing ‘metformin hydrochloride’ and investigate used active pharmaceutical ingredient. MFDS asked companies to report total number of drug items consisting of metformin substance, names and number of manufactured items, and names and number of non-manufactured items until Dec. 17. Molecular structure of metformin Pharmaceutical companies have to provide all information of items even covering ones in distribution at the moment, considering use-by date of complete products. For example, when an items’ use-by date is three years, then the item’s entire manufacturing record after December 2016 should be looked into. The ministry is also calling for a full report on active ingredients used in the metformin products. It means the ministry means to collect detailed information on DMF registration number and manufacturing plant of a complete product containing the ingredient under each serial number. The procedure resembles the ranitidine and nizatidine cases. When they find an issue in specific active ingredient and complete drug, the ministry can take a fast and accurate action based on the information submitted by companies. The pharmaceutical industry predicts the government direction is a part of the ministry’s preparation process, in case impurity is discovered in metformin medicine. Before the government body took an action on ranitidine and nizatidine cases, the ministry had reviewed detailed information on complete product and the active ingredients. MFDS had immediately ordered a sales ban on drugs with valsartan when Europe decided to recall the products, but it held back on the action for ranitidine and nizatidine until the thorough review on complete products and the ingredients was completed. The risk of metformin impurity broke out from Singapore. On Dec. 4, Singapore’s Health Sciences Authority (HSA) recalled three items out of 46 metformin containing drugs they investigated. The result confirmed contamination of N-Nitrosodimethylamine (NDMA) has surpassed daily acceptable level. Since then, the U.S., Europe and Japan initiated impurity testing on metformin drugs. All three regions are recommending companies to conduct self-testing on NDMA levels in their metformin drugs. ◆Companies initiating impurity self-tests and purchasing analyzer Companies in Korea are also encouraged to run self-tests on their metformin-containing items. So far the ministry has not officially instructed companies to test impurity in metformin ingredients. In fact, the ministry has not even ordered them to test NDMA level in complete product or announced a plan to collect all items for further investigation. MFDS’ lack of instruction could be because of the U.S. and Europe have not ordered for a recall on products with alarming impurity level, and also because the problematic metformin ingredient and complete product with the ingredient have not even been imported to Korea. Moreover, there has not been an official procedure of NDMA testing presented by the ministry. The complete products with contaminated metformin recalled in Singapore have not been imported to Korea, yet. However, it has not been confirmed yet if the active ingredient used in the recalled product has been used in Korea. Apparently, the Singaporean regulator has decided to recall the products after testing complete products, not the active ingredient. The pharmaceutical companies in Korea have no other choice, but to test their metformin products according to the active pharmaceutical ingredient impurity risk management measure the ministry has unveiled recently. While announcing the investigation result of nizatidine contamination last month, MFDS ordered companies to conduct a self-test on all of their synthetic active ingredients for impurity like NDMA. Accordingly, synthetic ingredient manufacturer and importer, as well as complete product companies, have to evaluate contamination risk in drugs either during manufacturing or storing processes. Pharmaceutical impurity risk management initiative unveiled by MFDS last month Moreover, pharmaceutical companies have to immediately report any discovery of impurity to MFDS after conducting self-evaluation on suspected items with risk of NDMA-like impurity contamination. Basically, metformin became the first substance to be ‘suspected for contamination risk’ since the ministry’s impurity risk management initiative. The industry seems to be in process of attempting self-analyze NDMA level in metformin medicine. However, the testing process has not been so simple without an official testing procedure and lack of laboratories with proper analysis equipment. Currently, only nizatidine-containing products verified with approved level of NDMA can be distributed, but the testing laboratories are unable deliver testing results in requested time as they are backed-up with all companies with nizatidine products. MFDS has ordered pharmaceutical companies to supply nizatidine-containing item with passing level of cancer-causing NDMA contamination (less than 0.32ppm), verified by testing done for each item serial number. The test can be done by Korean Good Manufacturing Practice (GMP) certified manufacturer, MFDS designated quality test institute, city and provincial-managed environment research lab and Korean Pharmaceutical Traders Association. MFDS ordered pharmaceutical companies to test NDMA level in nizatidine medicine before supplying Some of pharmaceutical companies are even considering on purchasing testing equipment to run it by themselves. But an analyzer costing up to 300 million to 500 million won, beside the six-figure annual maintenance, cost is definitely putting a strain on the company. A pharmaceutical company insider commented, “The company is taking account of equipping impurity risk examination system as its own quality management program. We are also discussing possibility of sharing an ownership and purchase cost of the analyzer”.
- Company
- Bayer Korea appoints Freda Lin as a new President
- by Eo, Yun-Ho Dec 13, 2019 10:59pm
- 프레다 린 대표 Bayer Korea has announced an appointment of Freda Ta-Ling Lin as a new President , starting from Jan. 1, 2020. The Korean branch’s top executive position has been vacant since the former President Ingrid Drechsel transferred to Bayer’s Turkish branch. From October, Bayer Korea’s Pharmaceuticals division has been managed by Lee Jina, a head of Cardiovascular Therapeutics Area. New President Freda Lin is a seasoned global leader in sales and marketing with 25 years of vast experience in the pharmaceutical industry. From 2013 to recent, Lin has been leading Bayer Taiwan as a head of Pharmaceuticals division and a President of the region. Previously, Lin has been building her career in the pharmaceutical industry as sales, market and strategic planning executive at GlaxoSmithKline’s Taiwan, China, Asia Pacific, and the U.K. branches. Moreover, Freda Lin is also to simultaneously serve as a head of Pharmaceuticals Division at Bayer Korea. New President Freda Lin said, “I am pleased to serve the role of President and to lead Bayer Korea in a country considered as one of the most innovative countries in the world”.
- Company
- Boryung Holdings appoints Kim Jung Gyun as New CEO
- by Eo, Yun-Ho Dec 13, 2019 10:59pm
- CEO Kim Jung Gyun Boryung Holdings recently convened a board meeting and appointed Chief Operating Officer Kim Jung Gyun as the new Chief Executive Officer. Joined Boryung Pharmaceutical in 2014 as a director, the new CEO Kim Jung Gyun served in Strategic Planning team, Production Management team, Human Resources team and was appointed as an executive director and COO at Boryung Holdings in January 2017. CEO Kim has contributed in increasing sales and improving profitability at Boryung Pharmaceutical by endeavoring on initiatives like ‘internal operational management system,’ ‘investment reprioritization,’ ‘generating open innovation-based new business like Vigen Cell’, and ‘building transparent and horizontal organizational culture’. As the COO of Boryung Holdings, Kim started establishing a holding company and subsidiary ‘Boryung Consumer’ since 2017, and shifted each business division to center board members for set a faster and transparent decision making process. Moreover, Kim reinforced collaboration system between board member executives to expand corporate value. Undergoing a series of changes, Boryung Pharmaceutical’s compound annual growth rate marked 7.1 percent in last three years, and its profitability has been significantly improved. The company is expected to make a record-high sales and operating profit this year. Besides, a vaccine manufacturer and biopharmaceutical R&D affiliate ‘Boryung Biopharma’ has also shown a steep growth and is expected to generate 100 billion won in 2019. CEO Kim stated, “As Korea is a part of top global markets, we should be the fastest to adapt to changes happening outside, constantly seek for opportunity in the global market, and invest on opportunity in future digital healthcare industry consisting of pharmaceutical industry, IT technology and healthcare”. Meanwhile, the current CEO of Boryung Pharmaceutical Ahn Jae-hyun resigned from his other position as a CEO of Boryung Holdings.
- Company
- MFDS to wait and see self-test results on metformin
- by Chon, Seung-Hyun Dec 13, 2019 06:34am
- Ministry of Food and Drug Safety (MFDS) The government seems to have decided to encourage pharmaceutical companies to run their own impurity contamination test on metformin drugs. Unlike the ranitidine and nizatidine incidents, the government means to wait and see the companies’ self-investigation results, rather than to take an action by itself. Basically, metformin would be the first substance to be applied with the recently unveiled impurity risk management initiative. However, the possibility still exists for the government to immediately call for sales ban and other follw-up measures, when a exceeding level of impurity is found in a product, either in Korea or overseas. According to the industry source on Dec. 12, Korea’s Ministry of Food and Drug Safety (MFDS) has not made any official order to pharmaceutical companies regarding findings of cancer-causing impurity in metformin. On Dec. 4, Singapore’s Health Science Authority (HSA) has decided to recall three out of 46 metformin products tested. Apparently, the regulator found N-nitrosodimenthylamin (NDMA) exceeding an acceptable level of daily consumption in metformin products. Since then, the U.S. and European health regulators have also started probing on contaminated metformin products. The U.S. Food and Drug Administration (FDA) is reportedly investigating NDMA discovered in metformin products available in the U.S. It also stated it would recommend recalling products with exceeding levels of NDMA contamination. The European Medicines Agency (EMA) has ordered companies to conduct NDMA contamination testing. Japan’s Ministry of Health, Labor and Welfare recently ordered metformin containing product manufacturers and importers in Japan to analyze and report risk of NDMA contamination in the substance and complete products. So far, MFDS has only stated it would “review investigation results”, and no other specific orders have not been given to the companies. The ministry has not yet ordered the companies to investigate NDMA in metformin active agent or complete product, nor has it stated the ministry would directly collect and investigate the substance. The ministry’s reaction is contrasting from the follow-up measures it had with other pharmaceutical impurity risk incidents. When the European regulator announced it would recall all valsartan products, the Korean ministry immediately banned sales of products with the same active ingredient. And after the sales ban was ordered in the U.S., the ministry once said “nothing to worry about”, but soon after it ordered an all-product ban. Actions on nizatidine followed the ranitidine sales ban. After collecting and testing active ingredient and complete product with similar chemical structure as ranitidine, MFDS banned sales on 13 items with unacceptable level of NDMA. It could be interpreted that the authority is trying to encourage companies to voluntarily test their metformin products. Neither of the U.S. or Europe has called for a recall due to exceeding level of the contamination. And the complete products reported with the impurity to date are not available in Korea, yet. MFDS official explained, “We have already asked companies to test the impurity in all products themselves”. It also means the recently introduced active ingredient impurity risk management initiative would be applied on metformin. In fact, MFDS has already asked pharmaceutical companies to run NDMA-like impurity test on all synthetic active agents, when announcing the investigation result of nizatidine medicine. Accordingly, synthetic ingredient manufacturer and importers, as well as complete product companies, have to evaluate risk of impurity contaminated during the process of manufacturing or storing. Pharmaceutical companies suspecting a risk of discovering NDMA and other harmful impurity in their product should immediately conduct a voluntary test and has to report MFDS as soon as possible when it is actually found. The impurity risk evaluation and testing should be conducted voluntarily, and the result of risk evaluation should reported by May 2020, and the result of test by May 2021. Pharmaceutical impurity risk management initiative presented by MFDS last month Since MFDS has introduced the impurity management initiative, metformin basically became the first case of ‘medicine with high risk’. In other words, MFDS is unlikely to test metformin itself, as of now. Moreover, metformin being a commonly used agent seems to make MFDS hesitant about testing the products proactively. Metformin is the most commonly prescribed first-line treatment for patients with Type 2 diabetes to control glucose level. In Korea alone, 642 of approved complete products contain metformin. Practically, all pharmaceutical companies have at least one metformin medicine. Compared to valsartan and ranitidine market, metformin has a far larger market volume. Pharmaceutical industry research firm UBIST reported outpatient prescription market volume of metformin product reached 420 billion won last year. It soared 63.4 percent in four years from 257.1 billion won in 2014. Currently banned ranitidine products generated about 200 billion won as outpatient prescription, but metformin market easily doubles the ranitidine market. A single dose of metformin is priced at less than a hundred one with reimbursement. Considering the pricing, metformin’s usage volume is overwhelmingly bigger than ranitidine. Yearly trend of outpatient prescription volume of metformin product (unit: KRW 100 million) Source: UBIST If the testing confirms metformin is contaminated with NDMA during the process of storing, active agent and complete product should be reviewed by each serial number. In such case, millions of serialized products would have to be investigated. It is physically impossible for MFDS to directly investigate them all. However, the ministry may initiate a full investigation, depending on the updates from home and abroad. The ministry’s hands-on investigation would be inevitable when active ingredient or complete product in Korea is found with exceeding level of impurity is reported from overseas. And even when a Korean company reports any case of NDMA contamination exceeding an acceptable level, full investigation is likely follow.
- Company
- Lilly releases first non-reimbursed 'Emgality'
- by Eo, Yun-Ho Dec 13, 2019 06:34am
- Eli Lilly's migraine new drug 'Emgality' was released in Korea. Lilly Korea announced on the 12th that it will release non-reimbursed CGRP-targeted migraines prevention drug, Emgality (Galcanezumab). This drug is a humanized monoclonal antibody that binds to the Calcitonin gene-related peptide (CGRP) molecule which plays a key role in causing migraine symptoms in the brain and blocks binding to receptors. .This is the first drug in Korea .Last year, after being approved for migraine treatment, it recently acquired additional FDA approval for episodic cluster headache treatment .The permission was granted for the EVOLVE-1 and EVOLVE-2 studies in which 1,773 people with migraine headaches (average migraine days 4-14 days per month) participated for 6 months, and chronic migraine patients (average headache days 15 days, migraine days 8 months or more) .The study was based on a REGAIN study involving 1113 people over 3 months .Through two clinical trials for episodic migraine patients, placebo of Emgality-treated patients for migraine treatment compared to baseline (9.2 days for Emgality group, 9.1 days for placebo group) across six months of clinic compared to average monthly migraine incidence for 6 months .Therapeutic benefit was proved .In particular, in the EVOLVE-2 clinical study involving Koreans, the average number of migraine headaches for 6 months in the Emgality group (226 patients) was reduced by 2 days (4.3 days in the Emgality group, 2.3 days in the placebo group) compared to the placebo group (450 patients) .Amgelity-treated patients who had 50% reduction in the number of days of migraine headaches over 6 months were 59% (36% placebo), 75% reduction were 34% (18% in the placebo group), and 100% reduction were 12% (6% in the placebo group) .Min-kyung Chu, neurology professor of Severance hospital, said “Migraine is a pain beyond our imagination that impairs the quality of life of patients, Patients who experience migraines more than four to five days a month can expect to improve their quality of life through preventive care .Emgality's launch is encouraging, with high blood pressure and epilepsy drugs being recommended for preventive treatment .Until now, high blood pressure medications and epilepsy medications have been recommended for preventive treatment” .Meanwhile, commercialization of CGRP-based therapeutics has been ongoing since last year .In addition to Emgality in the United States, drugs such as Aimovig (Erenumab) and Teva's Ajovy (Fremanezumab), which have been jointly developed by Novartis and Amgen, have entered the market.
- Company
- China okays Samsung’s Herceptin biosimilar Phase 3 trial
- by Lee, Seok-Jun Dec 11, 2019 10:20pm
- The Chinese health authority has green lit Samsung Bioepis’ first clinical trial in China. On Dec. 10, Samsung Bioepis announced China’s National Medical Products Administration (NMPA) has approved the company’s Phase 3 investigational new drug protocol on SB3, a biosimilar version of Hercpetin with trastuzumab. The first patient of Samsung Bioepis’ first clinical trial is scheduled to get treated in the first quarter of next year. The Phase 3 trial is planned treat 208 Chinese patients with breast cancer. Samsung Bioepis to initiate its first clinical trial in China (indicated in red) In February, Samsung Bioepis has signed a partnership contract with Chinese private equity firm C-Bridge Capital for clinical trial, government approval and commercialization in China. The recently approve clinical trial would be conducted along with C-Bridge Captial’s biopharmaceutical company, ‘AffaMed Therapeutics.’ Established in 2014, C-Bridge Capital is China’s topline healthcare-dedicated private equity firm. The company’s portfolio covers general healthcare service sectors including biopharmaceutical, medical device and diagnostics, and its current assets under management is approximately two trillion won. Besides SB3, Samsung Bioepis is to collaborate with C-Bridge Capital on conducting clinical trials, processing approval applications and launching SB11 (ranibizumab biosimilar, referencing Lucentis), SB12 (eculizumab biosmilar, referencing Soliris) and SB15 (aflibercept biosimilar, referencing Eylea) in Chinese market. Before inking the partnership with C-Bridge Captial, Samsung Bioepis has also inked another partnership with China-based biopharmaceutical company ‘3S Bio’ in last January to market SB8 (bevacizumab biosimilar, referencing Avastin) and some other pipelines.
- Company
- Hanmi’s diabetes pipeline still standing in the storm
- by Chon, Seung-Hyun Dec 11, 2019 06:47am
- Hanmi Pharmaceutical’s efpeglenatide with the title of the biggest license-out deal to date is going through harsh times before reaching the finish line. The company’s unbent commitment for the pipeline kept it alive, despite amending the license out agreement twice and the partner company shifting R&D pipeline focus. Although it seems to have international clinical trials on their way unaffected, the company is now concerned of change in global commercialization partner. Headquarters of Hanmi Pharmaceutical On Dec. 10, Hanmi Pharmaceutical’s stock price closed at 298,000 won with 6.88 percent drop from the day before. Hanmi Science also took a 4.57-percent fall. Experts see that news of Hanmi Pharmaceutical’s partner company, Sanofi looking for a partner to launch efpeglenatide may have intimidated the investors. ◆Efpeglenatide surviving albeit Sanofi’s R&D pipeline shake-up In fact, efpeglenatide’s development timeline has not been changed. Sanofi broke a news of acquiring a U.S.-based oncology R&D company Synthorx for USD 2.5 billion (approximately three trillion won) on Dec. 9, and elaborated its plan to shift the focus of R&D pipeline and management style. Sanofi official stated it would prioritize investment on oncology, rare disease, blood disorder and neurology, while it would cease researches on diabetes and cardiovascular disease. However, the multinational company’s news also included its plan to complete ongoing Phase 3 clinical trials of efpeglenatide, but not to pursue a efpeglenatide launch. At face value, Sanofi means to not commercialize efpeglenatide, but it also means the pipeline survived another major pivot in Sanofi’s R&D pipeline. The candidate drug is the only diabetes treatment pipeline among five investigational drugs the multinational company plans to submit the U.S. Food and Drug Administration (FDA) New Drug Application (NDA) for in two years time. A Sanofi executive stressed “It was the best decision for the successfully launch of efpeglenatide while maximizing the productivity of our research engine. It was irrelevant to efficacy and safety of the substance, and it would make no changes on license-in agreement with Hanmi Pharmaceutical”. Technically, efpeglenatide proved its potential to Sanofi’s new CEO, Paul Hudson appointed last August, despite his firm commitment to reprioritize R&D pipeline. In the year, Sanofi suddenly stopped research in a trigonal GLP-1/GIPR/GCGR agonist, SAR441255. And the French company also has paid back upfront fee to exit a 300-million-dollar partnership deal over SGLT1/2 dual inhibitor Zynquista (sotagliflozin) signed in 2015. ‘New Drug Application Submission Timeline 2019-2023’ unveiled during 3Q performance presentation by Sanofi ◆Amending license-out agreement twice, two LAPSCOVERY medicines returned Starting with the license-out agreement, efpeglenatide has gone through a series of ups and downs. Efpeglenatide, a GLP-1 injection for type 2 diabetes, is a bio drug candidate that extended once-daily administration interval to once-weekly and even once-monthly. It incorporated Hanmi Pharmaceutical’s key platform technology, ‘LAPSCOVERY’. LAPSCOVERY, or Long Acting Protein/ Peptide Discovery platform technology prolongs the duration of biologics’ short half-life to reduce administration frequency and dose, which would ultimately reduce adverse reaction and improve efficacy. Chemically conjugated biologics and protein ‘LAPS-carrier’ amplifies duration of the substance’ effect in human body and maintains the effect for maximum one month even with a small amount. In November 2015, Hanmi Pharmaceutical signed a license-out agreement with Sanofi on efpeglenatide, which still to this date is the biggest deal in the history of Korean pharmaceutical industry. The 2015 deal transferred technology of a EUR 3.9 billion-worth Quantum Project (efpeglenatide, long-acting insulin, and efpeglenatide with long-acting insulin) to Sanofi. The upfront fee alone was 400 million euro. But after closing the deal, a number of unexpected changes were made. In December of 2016, Hanmi Pharmaceutical amended the agreement to drop one of the drug candidates from the ongoing technology transfer project. Out of three drug candidates, Sanofi decided to return license over the long-acting insulin. Agreement terms on the long-acting insulin combination was also changed so that Sanofi would acquire it after Hanmi Pharmaceutical develops it for a certain period of time. As a result, Hanmi Pharmaceutical paid back 196 million euro out of Sanofi’s 400-million-euro upfront payment. The milestone payments were also affected and the overall deal was shrunk by over one billion euro, down to 2.82 billion euro. Regardless of the reduction, the upfront fee and overall scale of the efpeglenatide deal is still historic record high within the Korean pharmaceutical industry. Hanmi Pharmaceutical-Sanofi agreement revised in June (Source: Financial Supervisory Service) In June, however, Hanmi Pharmaceutical and Sanofi agreed to amend the agreement once again. Hanmi Pharmaceutical lowered the maximum co-research expense from 150 million euro to 100 million euro with about 50 million euro (approximately 65 billion won) cut. The first amendment actually included a clause for Hanmi Pharmaceutical to contribute 25 percent of efpeglenatide R&D expense, which was supposed to be covered entirely by Sanofi. And Hanmi Pharmaceutical set the research expense cap at 150 million euro. In just about two years, Hanmi Pharmaceutical was able to revise the clause added in 2016 to be more favorable to them. When amending the agreement for the second time, Hanmi Pharmaceutical also postponed its payment period of clinical trial expense. Initially, Hanmi Pharmaceutical was supposed to pay when Sanofi quarterly billed for efpeglenatide’s clinical expense. The additional expense of 40 million euro out of 68.5 million euro would be billed on an earlier date between September 2022 and submission date of Biologics License Application (BLA) to FDA. The bill is to be cleared by Hanmi Pharmaceutical within 15 days. The rest of 28.5 million euro would be paid on earlier date, either in September 2023 or the FDA approval date. Basically, Hanmi Pharmaceutical is to pay Sanofi whenever efpeglenatide development achieves a milestone. When Sanofi initiated large scale clinical trials on efpeglenatide, the expense soared more than expected. But then Sanofi seems to have accepted Hanmi Pharmaceutical’s request to lower its contribution in clinical expense. Meanwhile, risk factors in LAPSCOVERY technology have been raised. Janssen signed a technology transfer deal on JNJ-64565111, a candidate diabetic obesity drug, but it had to suspend clinical trial due to production delay. In July, Janssen returned its license on JNJ-64565111 and the license-out agreement covering two candidate drugs based on LAPDISCOVERY technology fell through. Spectrum Pharmaceutical’s in-licensed Rolontis, a neutropenia treatment, is the first LAPSCOVERY-applied medicine to get so close to commercialization. A U.S.-based Spectrum Pharmaceutical filed for FDA approval on Rolontis at the end of last year, but it dropped the BLA in March as the authority ordered for more supplementary data. The application was submitted again in October. ◆ Five out of two efpeglenatide clinical trials completed selecting participants Currently, the efpeglenatide development is going smoothly. Two years after signing the deal, Sanofi officially unveiled a detailed plan on efpeglenatide at the end of year 2017. By the end of 2017, Sanofi initiated the first Phase 3 clinical trial to compare efpeglenatide and placebo, and in April last year, the company initiated a large-scale Phase 3 trial to test efficacy and safety in treating cardiovascular diseases. Another Phase 3 trial was initiated since September last year to compare efpeglenatide and competing product Trulicity (dulaglutide) as a combination therapy with Metformin. In October last year, a protocol on combination therapy with efpeglenatide and basal insulin was registered, and in December same year, the fifth Phase 3 trial was initiated to confirm the drug treating Type 2 diabetic patients who cannot control glucose level either after Metformin single therapy or Metformin and sulfonylureas combination therapy. The overall target number of sample is 6,340. As of now, two out of five Phase 3 trials on efpeglenatide have gathered sufficient number of participants. Most recently, placebo-comparing Phase 3 trial AMPLITUDE-M has gathered targeted number of patients. The investigational drug’s key trial, AMPLITUDE-O testing effect of efpeglenatide on cardiovascular outcomes has registered more than planned number of participants of 4,076 patients in June. A Hanmi Pharmaceutical official stated, “Sanofi has promised to concentrate on completing numerous Phase 3 trials currently ongoing to develop efpeglenatide successfully”. Two Phase 3 efpeglenatide trials have registered enough number of patients (Source: ClinicalTrials.gov)
