Prof. Howard Lee proposed health insurance reimbursement for the combination therapy of DPP4 inhibitors and SGLT2 inhibitors, irrespective of their labels as approved by the Korea Ministry Food and Drug Safety (MFDS), at a special session organized by the Korean Diabetes Association (KDA), in association with its Spring Conference 2019, held on May 9-11, 2019, at the HICO, Kyeongju, Korea. Unlike other countries including the USA, EU, and Japan, MFDS in Korea has approved the combination therapy of SGLT2 inhibitors with other oral hypoglycemic agents, particularly with DPP4 inhibitors, only on the basis individual drugs, not on the therapeutic class. This unique regulatory approval has contributed to the delayed reimbursement of various combination therapies involving SGLT2 inhibitors since their approvals. 

The delayed reimbursement has caused a lot of debates not only between the pharmaceutical industry and the Health Insurance Review and Assessment Service or HIRA, but also among clinicians. With this background, the KDA asked Prof. Lee to share his perspectives from the points of drug regulatory science if the reimbursement for the combination therapy of DPP4 inhibitors and SGLT2 inhibitors on the basis of therapeutic class, not on the individual drug, has any scientific and clinical rationale. Prof. Lee, based on an intensive systematic literature review focusing on the pharmacokinetics, drug-drug interactions, clinical efficacy, and safety profiles of the combination treatment with DPP4 inhibitors and SGLT2 inhibitors, discussed that it is highly unlikely any combination of the two classes would interact in a clinically meaningful and significant way. Furthermore, Prof. Lee argued that it is very likely for every combination of a DPP4 inhibitor with an SGLT2 inhibitor to result in an additional, significant, and clinically meaningful decrease in HbA1c or glycated hemoglobin. However, since not every combination has been studied for its safety profiles although it is likely to be similar to those of monotherapy, Prof. Lee proposed to perform a real world data study under the auspice of KDA, sponsored by the pharmaceutical industry, to explore and confirm the safety and efficacy profiles of the combination therapy.      

Reflecting the interest in the reimbursement issue, the conference room was full of clinicians, industry representative, and journalists even though the session was presented early in the morning on Saturday. More detailed information on the session can be found here. 

Prof. Howard Lee emphasized the importance of the holistic approach to ensure the safe use of biological agents, particularly in the field of rheumatology, at a policy forum sponsored by the Korean College of Rheumatology, held at the Seoul Foreign Correspondents' Club, Press Center, on November 14, 2018. Biological agents, since first introduced in the late 1990s, have changed the way that physicians managed patients with various connective tissue diseases, of which rheumatoid arthritis is a typical example. "Because biological agents are way different from small-molecule drugs in terms of their safety profiles, which most physicians are not familiar with", Prof. Lee said, "they have to be used carefully, preferably only by those who were trained how to correctly prescribe them and those who are experienced in detecting the adverse reactions, which often clinically manifested in atypical forms." "Reactivation of latent tuberculosis and increased occurrence of opportunistic infections are some examples", Prof. Lee added. Registries of patients using biological agents can be a useful tool to track down and detect adverse effects of biological agents, which are not easy to be screened out in clinical trials before marketing approval. In that sense, Prof. Lee requested the rheumatology society to be more proactive by initiating and maintaining a series of safety measures, hopefully under a full collaboration with and support by the regulatory agency. Most of the panelists at the forum agreed with Prof. Lee. 

Prof. Howard Lee demanded that generic approval in Korea be tightened by not allowing the so-called 'joint-bioequivalence' or 'consigned-bioequivalence' route at a Korea National Assembly Forum, co-sponsored by Rep. Yoon Il-Kyu of the ruling Democratic Party and the Korean Doctor's Weekly. The forum was held to go over various regulatory issues associated with the recent recall of valsartan-containing anti-hypertensive agents by the Ministry of Food and Drug Safety in a haphazard way, prompted by a similar regulatory action by the European Medicines Agency, which was caused by a concern that the active ingredient manufactured by a Chinese company contained NMDA, which could be carcinogenic in humans.

According to Prof. Lee, there were at least three regulatory practices that could have prompted the valsartan debacle in Korea: too low bar for generic entry into the market, lack of a consistent quality assurance system to ensure the quality of generics and their sources (active pharmaceutical ingredients), and too generous pricing for generics. "These unique regulatory systems for generics in Korea have favored the incompetent generic maker to enter the market rather unruly", Prof. Lee emphasized. Prof. Lee added, "Many pharmaceutical companies, most which were not unsure of their quality, got generics approved through the join- or consigned-bioequivalence testing, and this system needs to be abolished."

More detailed story about the Forum can be found in the following articles in Korean or English. 

Three CCADD members (Dr. Jeong An Gim, Yoomin Jeon, and Tae Kyu Chung) attended the Pharma AI & IoT 2018 conference, held in London, UK, from July 11 through 12, 2018. Many invited from pharmaceutical companies, software firms, and universities spoke at the conference. The conference provided a comprehensive outlook on the key issues about artificial intelligence (AI), which has been actively adopted at the pharma and healthcare industry. AI-augmented human decision-making was the central theme of the conference. Dr. Margaret McDonald from Pfizer told the audience machine learning or AI would increase efficiencies in regulatory decision-making. She added, "Unsupervised AI may integrate enormous amounts of data and those real world data support regulatory decision-making about drug safety." Likewise, many attendants emphasized the importance of AI in their field of specialization. During the conference, attendants discussed and shared best practices in furthering AI technology development specific to the pharma and healthcare industry through inspiring presentations and network opportunities.

After the conference, the CCADD attendants visited several landmarks in London such as the Greenwich Observatory, Tate Modern museum, and London Eye. Amazing weather and the scenic view of London was a big plus. Visiting London was a great refreshing and learning opportunity.

Kim Y, Kim A, Lee S, Choi SH, Lee DY, Song JS, Lee H, Jang IJ, Yu KS. Pharmacokinetics, Safety, and Tolerability of Tedizolid Phosphate After Single-Dose Administration in Healthy Korean Male Subjects. Clin Ther. 2017. Sep;39(9):1849-1857, ePub 2017 Aug 31.

Lee H. Erratum to: Is Extrapolation of the Safety and Efficacy Data in One Indication to Another Appropriate for Biosimilars? AAPS J. 2015;17(6):1520-1521

Lee H. Is Extrapolation of the Safety and Efficacy Data in One Indication to Another Appropriate for Biosimilars? AAPS J. 2014;16(1):22-26, Epub 11 Oct 2013 DOI: 10.1208/s12248-013-9534-y

Chi YH, Lee H, Paik SH et al. Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Fimasartan, a Novel Angiotensin II Receptor Antagonist, Following Single and Repeated Oral Administration in the Fasted and Fed States in Healthy Subjects. Am J Cardiovasc Drugs. 2011 Oct 1. 1(5):335-46.