- by Eo, Yun-Ho Aug 7, 2020 06:28am
The competition ground among poly ADP ribose polymerase (PARP) inhibitors targeting BRCA gene has widened as Pfizer entered the South Korean market following the footsteps of AstraZeneca and Takeda Pharmaceutical.
According to the pharmaceutical industry sources, the Korean health authority approved of Pfizer Korea’s Talzenna (talazoparib), indicated to treat patients with germline BRCA (gBRCA)-mutated breast cancer, on July 30.
Unlike AstraZeneca’s Lynparza (olaparib) and Takeda Pharmaceutical’s Zejula (niraparib) with initial indication for treating ovarian cancer, Talzenna started off with the indication for treating breast cancer. Talzenna was approved as a single therapy to treat patients with gBRCA-mutated human epidermal growth factor receptor 2-negative (HER2-) locally advanced or metastatic breast cancer.
A PARP inhibitor, Talzenna suppresses PARP1 and PARP2 genes that produce proteins involved in DNA repair. As a result, the medicine hinders the DNA repair in gBRCA-mutated cancer cell and induces cancer cell death.
The latest approval was based on Phase III, open-label, randomized EMBRACA trial outcome that tested Talzenna against healthcare provider’s choice of chemotherapy in 431 patients with a gBRCA mutated and locally advanced or metastatic HER2- breast cancer, who may have received up to three prior chemotherapies.
The primary endpoint of EMBRACA trial evaluated median progression-free survival in Talzenna-only group (8.6 months) against chemotherapy group (5.6 months), and confirmed significant improvement made by Talzenna. The study also found the drug reduced the risk of disease progress or death by 46 percent more than the chemotherapy.
The key subgroup analysis among patients with triple-negative breast cancer, hormone receptor positive, and relapsed metastasis in central nervous system also confirmed the benefit of improving PFS. For the second endpoint objective response rate (ORR), the Talzenna group demonstrated 62.6 percent and doubled the chemotherapy group’s ORR at 27.2 percent.
Meanwhile, the two other PARP inhibitors in the market are already hectic preparing for the indication and healthcare coverage expansion.
Lynparza took the pharmacoeconomic evaluation-exemption route and settled on the expenditure cap type risk sharing agreement (RSA) in October 2017. It was initially listed for maintenance therapy in patients with ovarian cancer after chemotherapy, but it is now in progress of expanding healthcare coverage on indications&8212;first-line maintenance therapy in patients with BRCA mutated metastatic ovarian cancer, single maintenance therapy in patients with platinum-sensitive recurrent high-grade epithelial ovarian cancer, and in patients with HER2- metastatic breast cancer.
In late last year, Zejula was also listed as a maintenance therapy in patients with ovarian cancer who have received chemotherapy. Now the drug is seeking for reimbursement expansion as a maintenance treatment in gBRCA mutation-negative patients with recurrent epithelial ovarian cancer, who are in a complete or partial response to platinum-based chemotherapy, and also as a single therapy treating patients with relapsed ovarian cancer, who have received more than four chemotherapies.
However, the Cancer Deliberation Committee, the starting point of the coverage expansions, has been skeptical about Lynparza in mBRCA and Zejula in gBRCA-negative indications and denied the expansion.
- Kcab, compared clinical trial with Nexium
- by Lee, Tak-Sun Aug 7, 2020 06:27am
- HK inno.N's new domestic drug ‘Kcab’ is specifically compared with the reference drug, Nexium. The company said it will explore new indications through the trial.
The MFDS approved IND of Phase I clinical trial to explore the pharmacokinetics, Pharmacodynamic properties and safety of Tegoprazan twice a day dosing regimen in healthy subjects' submitted by HK inno.N on the 31st of last month. 64 healthy adults participated in this clinical trial.
It is interesting that the reference drug is Nexium injection. In clinical trials, Kcab is administered twice a day to compare the pharmacokinetic and pharmacodynamic properties of Nexium injections. Kcab is currently used in the market once a day.
AstraZeneca Korea's Nexium injection is a product administered intravenously once a day, and is mainly used when oral method is not appropriate.
A company official said, "This trial is for exploring new indications." If so, it is presumed to be for the purpose of acquiring the indications possessed by Nexium through comparing the equivalence with Nexium.
Accurate indications of Nexium are in the case of adult ▲when oral method is not appropriate, as an alternative to oral therapy, GERD with severe esophagitis or severe symptoms due to gastroesophageal reflux, ▲Prevention of rebleeding after endoscopic treatment of acute hemorrhagic gastric ulcer or duodenal ulcer.
In addition, for children aged 1 to 18 years, ▲ when oral method is not appropriate, it is used as an alternative treatment with erosive reflux esophagitis or severe GERD.
It is observed that Kcab are attempting clinical trials to obtain indications for 'prevention of rebleeding after endoscopic treatment of acute hemorrhagic gastric ulcer or duodenal ulcer'.
K-Cap is currently providing indications including antibiotic therapy for the treatment of H. pylori in patients with peptic ulcer and/or chronic atrophic gastritis, ▲ treatment of erosive GERD, ▲ treatment of non-erosive GERD.
Additional clinical trials for maintenance indications of patients with erosive GERD treatment confirmed through an endoscope and clinical trials to investigate the possibility of using NSAIDs in combination are also being conducted.
Kcab (Tegoprazan) is a P-CAB (Potassium-Competitive Acid Blocker)-based drug that has a mechanism of reversibly blocking a proton pump that secretes gastric acid from the stomach wall.
The industry analyzes that Kcab is leading the evolution of the P-CAB family by conducting clinical trials with PPI-based drugs such as Nexium as a reference drug. So far, PPI drugs have led the market in GERD related diseases.
Meanwhile, Kcap has successfully increased sales by recording an outpatient’s prescription amount of &8361;30.7 billion only in the first half of this year, based on UBIST.
- A big deal after various exchanges between companies
- by Lee, Seok-Jun Aug 7, 2020 06:27am
- Big Deal (License Out/LO) of the traditional pharmaceutical companies show that there have been various exchanges in the past. Looking at the recently established Hanmi and Yuhan’s technology transfer partners, it was because there were exchanges such as joint promotion in the past.
It was that exchanges in the past led to exchanges between research institutes of both companies, and even technology transfer.
Hanmi transferred NASH (non-alcoholic steatohepatitis) treatment, Efinopegdutide (HM12525A) to MSD USA at a scale of &8361;1 trillion (down payment of &8361;12 billion). It is an analysis that both companies' past ties were involved in the technology export contract.
The relationship between Hanmi and MSD goes back to 2009. At the time, the two companies signed a contract to export the hypertensive treatment drug Amosartan to over 50 countries under the brand 'Cozaar XQ'.
In 2016, the two companies signed Rosuzet's global export contracts in 23 countries, followed by Mexico this June.
An official at a securities company said, “We know that Hanmi has been working with MSD for several years to naturally exchange with the research institutes. There are more and more cases where the reliability accumulated from small exchanges extends to technology transfer”.
The 2015 large-scale technology transfer agreement between Hanmi and Sanofi is similar.
In 2013, the two companies jointly developed a high blood pressure/hyperlipidemic drug, Rovelito. It covers everything from product development to launch and marketing. Although there has been a change in the relationship between the two companies, including Sanofi's return of rights, there is no disagreement that past exchanges had a positive effect on LO.
Small exchanges among Yuhan and Beringer-Gilliard led to big deal
Yuhan Corporation is a similar case. Yuhan exported the pre-clinical (animal) NASH therapeutic substances to Beringer Ingelheim in July last year for a total of &8361;1 trillion ($870 million). It is a scale that competes for the level among the pre-clinical license agreements in the domestic pharmaceutical industry. The contract amount is $40 million (about &8361;45 billion).
In 2010, Yuhan entered into a co-promotional agreement with Behringer’s Twynsta, since then, additional treatments for diabetes treatment drugs, Trajenta and Jardiance, are underway. In the early stages, partnerships were expanded as the performance of early joint sale items improved.
The relationship between the two companies led to exchanges between research institutes. Based on the confidentiality agreement, they are sharing their research content with each other. In this process, in this process, it is known that exchanges with Yuhan's NASH treatment have also occurred.
This is the same as the big deal between Yuhan and Gilead that occurred in January of the same year. Yuhan transferred another NASH therapeutic substance to Gilead Sciences at the time of US$785 million (&8361;882.3 billion). The down payment is $15 million (about &8361;16.8 billion).
This case was conducted in the phase of candidate substance discovery. It turns out that it was impossible without the exchange between the two companies.
In 2012, Yuhan signed a co-promotional contract with Gilead's hepatitis B treatment drug, 'Viread'. Since 2017, it has been jointly selling various items such as hepatitis C treatment 'Sovaldi' and 'Harvoni', and HIV/AIDS treatment 'Stribild' and 'Genvoya'.
- Boryung eyes KRW 60 bln multiple myeloma drug market
- by Lee, Tak-Sun Aug 7, 2020 06:27am
- Boryung Pharmaceutical is taking bold actions to expand its share in the South Korea’s multiple myeloma treatment market valued at 60 billion won.
After signing a deal to supply a new drug in the Korean pharmaceutical market, the company is now challenging the original Pomalyst’s patent for the first time in Korea.
According to the industry sources on Aug. 5, Boryung Pharmaceutical filed a request for a negative confirmation of scope in Pomalyst capsule on July 31 to evade the original’s pharmaceutical substance patent.
Pomalyst, a product by Celgene, is currently dominating the biggest pie in the multiple myeloma treatment market. It was approved for sales in 2014, and received reimbursement from 2017 as a third-line therapy.
The drug is indicated to treat patients, who failed with the first-line treatment, Janssen’s Velcade, and show no response to the second-line treatment, Revlimid (lenalidomide). Revlimid is also developed and supplied by Celgene.
Boryung Pharmaceutical owns Velkin injection containing bortezomib. The injection was approved for the market in November 2015.
In October of the following year, Boryung Pharmaceutical inked an agreement with a Spanish-based pharmaceutical company PharmaMar to supply their multiple myeloma treatment Aplidin (plitidepsin) to Korea. The medication attracted attention recently with its benefit of preventing COVID-19 infection.
For the market approval in Korea, Boryung Pharmaceutical has submitted Aplidin’s Phase I trial protocol to Ministry of Food and Drug Safety (MFDS).
The Korean company seems to have challenged the Pomalyst patent to prepare development of follow-on drugs. If the court accepts the negative confirmation of the patent scope, Boryung Pharmaceutical would be able to release three products in the multiple myeloma treatment market.
Boryung Pharmaceutical is a rare gem in the Korean pharmaceutical industry with strengths in anticancer treatments. It owns originals like Gemzar and Xeloda, and it also supplies the number one follow-on drug Genexol. The industry is paying a close attention to the company on its path to secure a strong income source by strengthening the anticancer business with a variety of multiple myeloma treatments.
- SNUH participates in COVID-19 trials using Rebif
- by Lee, Tak-Sun Aug 7, 2020 06:27am
- Seoul National University Hospital participates in a multinational clinical trial using 'Rebif' (Interferon Beta-1A, Merck), which has recently been cited as a candidate for COVID-19 treatment.
Rebif is a pre-filled injection that is also approved in Korea. It is used for multiple sclerosis, and has recently been mentioned as a candidate for COVID-19 treatment in Europe.
The MFDS approved a multinational sponsor-investigator trials plan for 'multi-center, randomized, double-blind, placebo-controlled study on the safety and effectiveness of new drugs for COVID-19' submitted by Seoul National University Hospital on the 4th.
This clinical trial explores the effectiveness of a combination of Remdesivir and Interferon Beta-1A in admitted patients due to COVID-19.
There are 1,038 test subjects worldwide, and 100 will participate in Korea. Clinical trials are conducted at Seoul National University Hospital and Bundang Seoul National University Hospital.
This is the first clinical approval of COVID-19 using Rebif in Korea.
- SGLT-2 inhibitors growth surge by 30% in antidiabetic market
- by An, Kyung-Jin Aug 7, 2020 06:26am
In the South Korean oral antidiabetic drug market, the influence of sodium-glucose cotransporter-2 (SGLT2) inhibitors has expanded even further. The outpatient prescription sales in the medicine broke through the 50-million-won point as the single drug prescription is constantly growing and combination therapies have been effective. AstraZeneca and Boehringer Ingelheim, both owning SGLT-2 inhibitor single drug and combination drug, are strongly leading with 95 percent of the market.
According to a pharmaceutical market research firm UBIST on July 31, six SGLT-2 inhibitor single drugs and combination drugs have raised 57.4 billion won in the first half of the year from outpatient prescription, surging 30.8 percent from last year same time at 43.9 billion won. Also compared to the first half of 2018 making 32.2 billion won, this year’s prescription sales soared by 78.2 percent.
The antidiabetic medicine SGLT-2 inhibitor hinders reabsorption of blood glucose in kidney and induces excretion of the unused glucose through urine, which eventually lowers the glucose level in the blood. Unlike dipeptidyl peptidase 4 (DPP-4) inhibitors, the SGLT-2 inhibitors do not rely on insulin nor get affected by insulin resistance. Also the users have been positive about the medicine’s clinical evidence of weight loss effect and benefit in cardiovascular system.
AstraZeneca and Boehringer Ingelheim have launched SGLT-2 inhibitor combination drugs following their single drug line-ups and started expanding the SGLT-2 inhibitor prescription.
In the first half of the year, AstraZeneca’s Forxiga (dapagliflozin) generated 17.6 billion won in outpatient prescription and grew by 10.1 percent from last year. After signing a partnership deal with CJ Healthcare in September 2014, AstraZeneca released the first SGLT-2 inhibitor Forxiga in the Korean market. The new drug kept the leadership in SGLT-2 inhibitor market for six consecutive years since then. AstraZeneca is now claiming more of the market influence by becoming the first company to release SGLT-2 inhibitor plus metformin combination drug Xigduo. The combination therapy has raised 13.4 billion won in the first half of the year, which was 42.5 percent higher than last year.
From 2018, AstraZeneca has started co-marketing Forxiga and Xigduo with a Korean partner Daewoong Pharmaceutical. The two drugs together have generated 31 billion won, taking up 54.0 percent of the market share. The research firm evaluated the global company’s early move and the Korean company’s sales forces have created a synergy effect.
Boehringer Ingelheim’s Jardiance (empagliflozin) is the first SGLT-2 inhibitor to prove the benefit in cardiovascular system through EMPA-REG OUTCOME data and it is tailgating its biggest competitor closely.
In the first half of the year, Boehringer Ingelheim’s Jardiance has made 16.8 billion won in outpatient prescription. With the growth of 66.7 percent from last year, the gap between the drug and the market leader Forxiga was narrowed down to 800 million won. A metformin combination drug Jardiance Duo have increased this year’s prescription volume by 150.6 percent from last year and generated 6.8 billion won.
Boehringer Ingelheim’s Jardiance and Jardiance Duo have jointly made 23.6 billion won in the first half of the year and claimed 41.4 percent of the market. Considering AstraZeneca and Boehringer Ingelheim respectively took 68.0 percent and 27.6 percent of the SGLT-2 inhibitor prescription market, Boehringer Ingelheim’s market influence has surged immensely in a year. Currently, Boehringer Ingelheim’s Jardiance and Jardiance Duo are co-marketed under the joint partnership with Lilly Korea and Yuhan.
Astellas Pharma and MSD’s SGLT-2 inhibitor single drugs have shown a growth in prescription, but their market shares are still comparatively underwhelming. Astellas Pharma’s Suglat (ipragliflozin) has raised 1.6 billion won in the first half of the year with a growth of 16.7 percent from last year, but its market share is only at 2.8 percent. The company signed a co-marketing deal with Handok in April 2018 for the Korean company to be in charge of distribution, marketing and sales in Korea.
MSD jumped into the SGLT-2 inhibitor market in late 2018 with Steglatro (ertugliflozin), but it has not been prominent. The drug made 1.1 billion won in the first half of the year. Compared to last year, the figure doubled but it only has the smallest 2.0-percent pie in the prescription market. Prior to the launch of Steglatro, MSD signed a co-marketing deal with Chong Kun Dang, which they have already formed a partnership over Januvia (sitagliptin). Although MSD and Chong Kun Dang together have made Januvia the number one DPP-4 inhibitor, Steglatro could not break away from the handicap of joining the competition late.