- by Jan 28, 2021 05:59am
AstraZeneca’s Forxiga has been approved in South Korea to treat diabetes and heart failure. The indication is obtained for the first time for a sodium-glucose co-transporter-2 (SGLT2) inhibitor.
The industry experts noted, “Forxiga demonstrated reduction of cardiovascular death risk and hospitalization for heart failure in patients with or without diabetes.”
In 2014, Forxiga was the first SGLT-2 inhibitor to be released in the South Korean market. Although initially developed as a type-2 diabetes treatment, a series of clinical studies showed a potential in reducing risk of cardiovascular and renal diseases. And in last December, the drug won the indication to lower the risk of heart failure based on additional study results.
During a virtual online media conference convened on Jan. 25 by AstraZeneca Korea, experts projected the SGLT-2 inhibitor would bring a new change in the heart failure treatment scene.
Mediating the conference, President Choi Dong-ju (Seoul National University Bundang Hospital Department of Internal Medicine) of the Korean Society of Heart Failure (KHFS) evaluated, “A SGLT-2 inhibitor acquiring an indication to treat heart failure holds a great significance. Along with the changes in drug use, the global cardiology association’s guidelines are changing accordingly as well.”
In fact, the American College of Cardiology (ACC) has released the 2020 Expert Consensus Decision Pathway recommending cardiologists to choose SGLT-2 inhibitor of glucagon-like peptide 1 receptor agonists (GLP-1RA) over the previously recommended metformin, to treat patients who have been diagnosed with or have a high risk of cardiovascular disease.
Also the practical guidance for cardiologist updated after four years recommends administering SGLT-2 inhibitor combination as a standard of care (SOC) for NYHA class II-IV patients who meet the estimated glomerular filtration rate (eGFR) standard and have heart failure with reduced ejection fraction.
Professor Choi Seonghoon (Hallym University Medical Center Department of Cardiology) stated, “Particularly, the revised ACC guideline positioned SGLT-2 inhibitor as a second-line therapy for heart failure. Considering various efficacies Forxiga has confirmed, it would be helpful to use the drug as soon as possible for better treatment result.”
The Phase III DECLARE-TIMI 58 study, evaluating Forxiga’s cardiovascular safety in type-2 diabetic patients, confirmed the drug reduced the risk of hospitalization for heart failure or cardiovascular death. And DAPA-HF study proved the drug’s effect to treat chronic heart failure patients regardless of type-2 diabetes.
Professor Choi Seonghoon elaborated, “The DAPA-HF study presented highly significant data showing Forxiga lowering the risk of worsening heart failure by 30 percent, and the risk of cardiovascular death by 18 percent, especially because the clinical data proved the simple but integral benefit of combining Forxiga on the standard of care.”
Another participant at the conference, Professor Kim Eung-ju (Korea University Guro Hospital Cardiovascular Center) positively highlighted Forxiga can provide double benefit as it was effective in renal disease, most frequently expressed in patients with heart failure.
Professor Kim said, “In the DECLARE-TIMI 58 study, Forxiga lowered the eGFR by minimum 40 percent, compared to placebo, and the risk of renal disease death by 59 percent. Considering cardiovascular and renal diseases are closely related, SGLT-2 inhibitor could deliver a dual effect in heart and kidney.”
Led by Forxiga, the SGLT-2 inhibitor prescription volume is expected to surge even higher as it expands indication.
According to UBIST, the SGLT-2 inhibitor market generated 121.4 billion won last year. Compared to 12.2 billion won made in 2015, the prescription volume skyrocketed by 895 percent in just five years. Out of the total prescription volume, AstraZeneca’s Forxiga combination drug with metformin Xigduo takes up the biggest pie with 64.8 billion won.
- “34 years in drug industry, but now as a law firm advisor"
- by Eo, Yun-Ho Jan 28, 2021 05:59am
- A new advisor at Kang Han Law, Kwon Jaehong has 34 years of a long experience in the pharmaceutical industry.
After joining JW Pharmaceutical sales department in 1998, Kwon moved to Bristol Myers Squibb (BMS) Korea in 1998 and was leading the Government Affairs and Market Access businesses until last August. But as he retired, he left the corporate boundary.
And from this January, he wide opened the door to a law firm. While law firm recruiting a pharmaceutical industry specialist is becoming a latest trend, a global pharmaceutical company’s former government affair director joining a law firm holds a greater level of significance.
Daily Pharm interviewed Advisor Kwon at Kang Han Law office in Seoul.
“I do not think I would do ‘something groundbreaking.’ But I have been in the center of the communication among pharmaceutical company, government, patient group and healthcare providers for over two decades, which gave me a deeper insight on their perception gap and problem solving measures. Based on those experiences, I want to contemplate on what role I could play here.”
Behind his humble words, there were prudence and aspiration. In fact, the law firm has a clear agenda in specifically recruiting him.
It is quite different from recruiting a high-level government officer as an advisor from the Ministry of Health and Welfare (MOHW) and the Ministry of Food and Drug Safety (MFDS). These days, South Korean law firms are concentrating on offering a ‘total consulting service for drug pricing,’ covering drug approval, reimbursement application, pharmacoeconomic evaluation (PE) designing, risk sharing agreement (RSA) and PE exemption.
Advisor Kwon’s expertise surely meets the need. When he was at BMS, he participated in the National Health Insurance (NHI) listing procedure for blockbuster new drugs.
He led the talks on the NHI reimbursement listing and expansion on a blockbuster hepatitis B virus treatment Baraclude, a “super-Gleevec” Sprycel, and a novel oral anticoagulant Eliquis. Also he handled a blockbuster antiplatelet drug Plavix, a first-in-class oral hepatitis C virus treatment Daklinza-Sunvepra, and an immunotherapy Opdivo.
As a representative from Korean Research-based Pharmaceutical Industry Association (KRPIA), he also participated in talks for major regulatory reform changes in reimbursement listing and drug pricing, such as introduction of positive listing, selective listing, RSA, PE exemption and lump-sum pricing reduction.
“I don’t want to limit myself to pharmaceutical reimbursement listing. The regulations are ever changing. Projecting and preparing for prospective changes takes a vast part of pharmaceutical business. I could provide a help in the process and each phase of adapting to the change, and also I could set up blueprints for now my colleagues and fellow advisers to better understand the industry.”
Technically, Kang Han Law is not a major law firm like Kim & Chang and Lee & Co. Also the firm does not even have a team entirely dedicated for healthcare. But as a law firm specialized in healthcare, it has been handling administrative law suit related to the healthcare authority regarding drug pricing.
“As I would be working alongside with expert attorneys and advisors, I’m positive we would be able to create a synergy effect. The healthcare sector is directly related to patients, but its regulations are tight and often it finds various variables, which makes it quite interesting. I would do my best to strive for positive outcomes along with my competent colleagues.”
- Leclaza’s lightning fast listing shocks global competitors
- by Eo, Yun-Ho Jan 27, 2021 06:15am
- As Yuhan Corporation dashes for the National Health Insurance (NHI) reimbursement talk on Leclaza (lazertinib), affected multinational pharmaceutical companies are tensing up.
A Korean-made new drug Leclaza is to get reviewed by the Cancer Deliberation Committee in February, the related industry sees that the non-small cell lung cancer (NSCLC) treatment area would face a dynamic change sooner than expected.
Especially, the targeted therapies waiting for reimbursement listing or expansion are closely following the progress of Yuhan’s third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) Leclaza.
◆ Cyramza combined with a first-generation TKI: The industry projects two drugs would be impacted the most by the Korean-made drug. Lilly’s Cyramza (ramucirumab), one of the two drugs, is currently seeking for reimbursement expansion for a combination therapy with a first-generation EGFR TKI Tarceva (erlotinib).
The Cancer Deliberation Committee is to be convened for the first time this year today Cyramza-Tarceva combination therapy
Leclaza was first indicated as a second-line therapy for lung cancer treatment, which differs from the first-line therapy indication Cyramza combination therapy is targeting. However, Leclaza is also planning to acquire the first-line therapy indication, and its market influence would grow fast in Korea, considering the speed of approval and listing procedure it showed and its title of a Korean-made new drug.
Meanwhile, patients are showing great interest in the combination of vascular endothelial growth factor receptor-2 (VEGFR-2) antagonist Cyramza, EGFR TKI Tarceva and two targeted therapies as it showed efficacy in patients with EGFR exon 19 deletion or exon 21 mutation, although it used to demonstrate comparatively weak efficacy before.
◆Same generation same class Tagrisso: Technically, AstraZeneca’s Tagrisso (osimertinib) would be the biggest competitor to Leclaza.
Approved for the South Korean market in May 2016, Tagrisso is also categorized a third-generation EGFR TKI, same as Leclaza, and in December 2017 it received the NHI reimbursement for the second-line therapy indication Leclaza is applying for.
Tagrisso, also adding a first-line therapy in December 2018, attempted to expand the reimbursement in 2019, but the Cancer Deliberation Committee in October that year deferred the decision until the Phase III FLAURA trial outcome is published to confirm the overall survival as a first-line therapy.
However, the committee refused to approve the drug again noting the issue of the hazard ratio in the Asian subset analysis submitted along with the final findings of FLAURA. AstraZeneca is hoping to convince the committee with the FLAURA China study conducted with Chinese participants, but the review schedule has not been set.
If Leclaza is to enter the market right now, Tagrisso would have to compete against it in the same class. With a record-breaking speed of NHI reimbursement progress, Leclaza may shake up the South Korean targeted therapy market for lung cancer.
Currently, first-generation AstraZeneca’s Iressa (gefitinib) and Roche’s Tarceva, second-generation Giotrif (afatinib) and Vizimpro (dakomitinib), and a third-generation AstraZeneca’s Tagrisso are prescribed to patients as EGFR TKI.
- Can COVID-19 vaccine by the COVAX be quickly introduced?
- by Lee, Tak-Sun Jan 27, 2021 06:15am
- The health authorities said that it is possible to quickly introduce COVID-19 vaccine supplied from the COVAX Facility.
This is because the MFDS has been participating in the COVAX Facility vaccine joint review since October at the request of the WHO. Pfizer's vaccine was pre-verified on the 31st of last month when the WHO approved Emergency Use Authorization. This is why the government believes that rapid vaccination is possible by receiving the Pfizer vaccine from the COVAX Facility in early February.
The MFDS announced in a report from the President on the 25th that it is participating in the joint review of the COVAX Facility’s COVID-19 vaccine at the request of the WHO in October.
Pfizer's mRNA vaccine has been reviewed, and 13 items will be reviewed.
In fact, on the 31st of last month, the WHO Emergency Use Authorization of the Pfizer vaccine. On the 22nd, it also signed a contract for 40 million doses of Pfizer vaccine for the use of the COVAX Facility. It is expected to be supplied to member countries that have joined the COVAX Facility from February. The case of Korea is also being discussed.
Korea has signed a vaccine supply contract for a total of 1,000 people with COVAX Facility. Among them, 50,000 Pfizer’s vaccines are expected to be introduced first in early February.
However, Pfizer’s vaccine has not been approved in Korea, so it is possible to introduce it in an emergency only through special imports. Until now, special imports have been mainly applied to small amounts of imported products such as orphan drugs and essential drugs. However, last year's COVID-19 treatment 'Remdesivir' could be introduced urgently due to an infectious disease.
However, it is said that it is impossible to apply special imports for imported vaccines that do not have domestic clinical cases or screening history.
In response, the MFDS explained that vaccines supplied from the COVAX Facility can be considered for special imports because Korean examiners participated in the joint review.
An official from the MFDS said, “In the case of vaccines supplied through the WHO, examiners of the MFDS have participated in the quality certification evaluation. At the request of WHO, we have been participating in the WHO quality certification evaluation of COVID-19 vaccine since last October. Because I participated in the review, it will be used as a reference when deciding on special import.”
It is explained that this situation was also reflected by the MFDS' description of the WHO joint review situation in the data of the President's report.
It is interpreted that if the introduction of COVID-19 vaccine is confirmed by the COVAX Facility in early February, it is highly likely to follow special import procedures. Special import is determined by the KCDA through expert advice, etc. Special import is possible after 3-4 days of procedure.
Pfizer's vaccine applied for official approval from the MFDS on the 25th. Since it plans to complete the approval review within 40 days with as early as possible, item approval is expected in early March. The government has signed a contract with Pfizer to bring in COVID-19 vaccine doses for 10 million people of the third quarter.
- NOAC prescription market growth stagnates
- by Kim, Jin-Gu Jan 27, 2021 06:15am
- The novel oral anticoagulant (NOAC) market seems to be plateauing after enjoying consistent two-digit growth for years. The outpatient prescription market marked a growth of almost 20 percent until 2019, but the growth shrunk down to 3 percent last year.
Regardless of the decreased growth, Lixiana is still topping the market. Except for the market leader, the prescription performance by Xarelto, Pradaxa and Eliquis have dropped. The generics entering market seems to have critically affected Eliquis making a negative growth for the first time last year. Its generics are expanding their market presence from the second quarter in 2019.
◆NOAC market grows 3 percent making 184.3 billion won
According to pharmaceutical market research firm UBIST on Jan 25, overall the last year’s NOAC market generated 184.3 billion won with a growth of 3 percent from the year before.
The overall market volume expanded, but the growth was sluggish compared to previous years.
Since the launch of Xarelto in 2009, the NOAC market welcomed Pradaxa and Eliquis in 2013, as well as Lixiana in 2016. Replacing the older generation anticoagulant warfarin, the NOAC rapidly got bigger.
In last six years, the NOAC market generated 34.5 billion won, 80 billion won, 114.9 billion won, 151.5 billion won, 179 billion won and 184.3 billion won in year 2015 through 2020, respectively.
Its streak of two-digit growth was crippled last year with 3 percent, after seeing 132 percent, 44 percent, 32 percent and 18 percent growth in 2016 through 2019, respectively.
◆Lixiana growth by 7 percent, when Xarelto, Eliquis and Pradaxa drop
The market’s star items showed contrasting performance. Only the prescription volume of Lixiana by Daiichi Sankyo expanded, when all three others underperformed.
Generating 59.9 billion won and 64 billion won in 2019 and 2020, respectively, the Lixiana prescription volume had a 7-percent growth. The drug may have been the last to join the market, but it topped the market in 2019 and is still widening the gap with the runner-up.
The pharmaceutical industry analyzes the co-promotion deal signed with Daewoong Pharmaceutical is the key to the growth surge. In December of 2015, right before the product launch, Daiichi Sankyo inked the Lixiana co-promotion contract with Daewoong Pharmaceutical. The contract is still effective today.
Xarelto, on the other hand, had two consecutive years of negative growth. Its prescription volume peaked in 2018 with 52 billion won, the volume has been on a downhill since 2019 making 50.8 billion won. Last year the drug’s volume dropped again to 50 billion won. The industry experts project it would go under 50 billion won this year.
Eliquis also continued to make growth until 2019, but it turned downward last year. In year 2016 through 2020, the drug’s prescription volume hit 19.5 billion won, 30 billion won, 40.4 billion won, 49 billion won and 47.7 billion won, respectively.
The industry experts point out the generics is the culprit of the plateauing growth. Since June last year, generic versions of Eliquis like Chong Kun Dang’s Liquisia, Yuhan’s Yuhan Apixaban, Samjin Pharm’s Elxaban, Hanmi Pharamceutical’s Apixban, Aju Pharm’s Eliban and YooYoung Pharmaceutical’s Yupix have been released to the NOAC market.
The total prescription volume of Eliquis generics surged from 1.2 billion won in 2019 to 8.3 billion won in 2020. In last year, Liquisia, Elxaban and Yuhan Apixaban respectively generated 2.6 billion won, 1.7 billion won and 1.1 billion won. Taking account of the inclining quarterly prescription volume, the experts project they would break through the 10 billion won mark this year.
Since 2016, Pradaxa’s prescription volume has been dropping. The volume plummeted to 14.3 billion won last year. Compared to 18.1 billion won in 2019, it took a 21-percent drop. Boehringer Ingelheim signed a co-promotion deal with Boryung Pharmaceutical from 2018, but it has not been so effective.
◆Generic versions of Xarelto and Pradaxa ready for launch
And in this year, Xarelto and Pradaxa’s generics are to be released to the market and accelerate the shift in the NOAC market.
First, four companies that overcame NOAC Pradaxa’s patent are to release their generics early. Intro Bio Pharma’s Dabican, Aju Pharm’s Dabitran, Jinyang Pharm’s Pradabi and Huon’s Hubitran are preparing for the launch. The four companies won the patent dispute against the original drug company Boehringer Ingelheim in January 2019. The obtained preferential sales rights are to last until April 2022.
Another NOAC, Xarelto is also expecting its generic versions&8212;Hanmi Pharmaceutical’s Riroxban and SK Chemical’s SK Rivaroxaban&8212;to emerge in October. If Chong Kun Dang, successfully evades the product patent before Oct. 4, it would be able to market the product even before Hanmi Pharmaceutical and SK Chemical regardless of the preferential sales rights.
- 11 companies won consecutive patent disputes for Betmiga
- by Kim, Jin-Gu Jan 27, 2021 06:15am
- In the patent dispute over Betmiga PR (Mirabegron), an overactive bladder treatment with an annual prescription amount of ￦65 billion, generic companies won the first trial.
From the standpoint of generic companies, including Hanmi and Chong Kun Dang, which have already launched generics, and are about to release generics, the obstacles related to patents have disappeared. However, It is highly likely that the original company Astellas will choose to go to the Supreme Court.
◆Use patent·crystal patent invalidated
On the afternoon of the 22nd, the Patent Court of Korea ruled against the plaintiff (Astellas) in a lawsuit filed by Astellas against 11 companies including Hanmi and Chong Kun Dang. Following the first trial, the second trial also took the side of generics.
Original and generic companies have been fighting over Betmiga PR's crystal patent and use patent. Legal disputes have been fierce for four years since Hanmi and others filed an invalidation trial in March 2015.
In the end, the conclusion of the first trial was concluded in December 2019. Generic companies won use patents and some won crystal patents. As a result, Astellas took the case to the second trial, and at the second trial decided that both patents were invalid.
◆Generic exclusivity expires next month
The ruling was to sell generics for Betmiga. the material patent expired in May last year. The composition patent, which expires in 2029, has also been successful by Hanmi. This trial decision was confirmed without appeal to Astellas. The patent invalidation was confirmed in the second trial following the first trial, making it easier for generic companies to sell generics.
There are currently two products on the market. Hanmi and Chong Kun Dang received generic exclusivity and launched Mirabek and Selebeta respectively in June and July of last year. By the end of last year, the two companies had recorded outpatient prescriptions of ￦2.8 billion and ￦1 billion respectively.
The generic exclusivity of the two companies expires on February 3, this year. After the expiration of generic exclusivity, 9 companies including Daewoong can participate in the generic market.
However, if Astellas disagrees with the second trial decision and decides to go to the Supreme Court, it will be a burden for companies preparing to release generics. Regarding this, a pharmaceutical industry patent official said, "There is a high possibility that Astellas will lead the case to the Supreme Court."