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Welcome to "Luye Leadership Interview" – a new column featuring the Luye People Global Electronic Magazine! In each issue, we will invite one or more Luye leaders to share their insights regarding the company's business priorities and development strategies. "Spreading key insights and passing along ideas" is the goal in launching this column, with a lot of exciting content to follow...
This issue’s guest: Dr. Li Youxin, Head of Global R&D, Luye Pharma
Dr. Li Youxin, Head of Global R&D, Luye Pharma, delivering a speech
at the 13th Chinese Pharmaceutical Conference
Recent progress in innovative drugs was headlined at the 13th Chinese Pharmaceutical Conference, hosted by the Chinese Pharmaceutical Association, where expert participants noted: "Chinese drug innovations, with long-acting sustained-release preparations, targeted preparations and other new preparations are an emerging breakthrough, with much to be done in the future."
As a pioneer in the new pharmaceutical industry in China, Luye Pharma has been tirelessly exploring how to best innovate and globalize for more than ten years. These efforts are now bearing fruit: the NDA for risperidone extended-release microsphere for injection (LY03004) has been submitted to and accepted by the U.S. FDA, and it is expected to become the first Chinese innovative drug to be approved for sale in the United States. In terms of the R&D pipeline, Luye has several innovative drugs at the late stages of clinical development both in China and abroad. There is no doubt that Luye Pharma is now able to compete with the best all over the world in its focused treatment areas!
We can’t help but ask ourselves two questions. With so many new drug research and development fields, why do we focus on ‘innovative medicines’? Also, with so many ways to globalize, which is best for Luye Pharma?
We interviewed Dr. Li Youxin, Head of Global R&D at Luye Pharma, at the Chinese Pharmaceutical Conference for his answers to these questions.
Q:What are the pain points that innovative medications address?
A: To answer this question, we need to look at the actual situation of China's pharmaceutical industry. At the moment, China is still largely focused on generic drugs, and while it is transitioning from drug imitation to “innovation imitation,” original innovation is very rare.
Across the global industry original innovation is usually driven by small companies, through the incubation of venture capital, and then large companies will acquire these small companies or projects to develop the products. This model has become very mature in the United States. China is also building such a mechanism, but before this mechanism is mature, progress with original innovations is tough.
So, in which areas can China's new drug R&D strive to go? First, look at “me-too drugs,” which can alleviate the problem of "high drug prices." Due to the similarity between me-too drugs and brand name drugs, their entry into the market can break the monopoly of brand name products, pushing drug prices lower. It is a good thing from the perspective of drug accessibility, but because these drugs don’t provide any novel clinical benefits, patients aren’t better off apart from the access issue.
The other direction is the modification or improvement of innovative drugs. The goals of this are very clear, focus on the shortcomings of a product and follow up with targeted improvements to provide patients with more meaningful clinical benefits.
Taking the innovative drug Lipusu (paclitaxel liposome) as an example, Lipusu has successfully improved upon clinical defects of the original drug Taxol (Paclitaxel) by using liposome and targeted drug delivery technology. Lipusu encapsulates the poorly water soluble paclitaxel in a bi-molecular layer of liposomes, no longer using the polyoxyethylated castor oil and anhydrous ethanol solvent mix prone to cause severe allergic reactions. The unique therapeutic effect of paclitaxel is maintained, thus paclitaxel overall is now safer, with reduced adverse reactions.
The transformation and evolution of China's pharmaceutical industry has ushered in a “spring” of new drug development, but in order for China's new drugs to go international, it is first important to provide differentiated, clinically valuable products. To improve upon defects among listed products, addressing unmet clinical needs in the process, is an effective way to do this. It is also the direction that Luye’s R&D work has taken.
Q: Are Luye’s new products mainstream in foreign countries or niche products?
A: At present, the domestic healthcare industry is dominated by R&D into new drugs, while investment in pharmaceutical formulations is not strong. In contrast, foreign countries have attached great importance to the development of new pharmaceutical formulations. According to data from international markets, among the new drugs approved by the U.S. FDA each year, about 20% are innovative drugs and about 30% are generic drugs. The remainder, which accounts for the largest percentage, are modified versions of existing drugs. This is because in order to get on the market as quickly as possible and enjoy first mover advantages, new drugs will generally have room for improvement, meaning there’s also room for improvement in terms of clinical outcomes for patients.
Based on the U.S. FDA's registration classification system, a modified version of a previously approved drug is classified as new drug under 505(b)(2). In 2016, China's State Food and Drug Administration adopted the international standard to classify “a modified version of an approved drug” as a Class II New Drug. Both China and the United States are putting heavy emphasis on improvements to approved drugs.
Even as the capability for original innovation among Chinese pharmaceutical companies increases, improvements to listed products will continue to occupy an important area, because the “improvements” here are improvements in the value of the products themselves and in their benefit to patients.
Q: How competitive is Chinese novel drug delivery technology in international markets?
A: The enthusiasm for drugs to achieve Class 1 innovative status has continued to rise. Unfortunately, very few new Chinese drugs have been approved in the United States. LY03004, as the first innovative medicine from China accepted by the U.S. FDA for NDA review, has received much attention from the industry. Development of LY03004 started 10 years ago, and it is targeted at the international mainstream pharmaceutical markets such as the United States, Europe, Japan, and China.
In review of the development strategy for LY03004, identifying its market positioning is key. Based on the unmet clinical needs, differentiated products are developed to make up for the gaps in other countries’ markets. The clinical pain point for LY03004 to address is very clear: the requirement for oral administration to patients in the first three weeks. The commercially available risperidone injections need to be administered with a complementary oral administration in the first three weeks, but due to the individual physiological differences between patients, the drug may have a different release rate in the human body, leading to a risk of high plasma concentration. In response to this, clinical patients in the U.S. are usually hospitalized for observation during the third week of oral administration, which incurs additional treatment costs. However, patients receiving an injection of LY03004 do not need oral administration in the first three weeks, and steady-state plasma concentration can be reached more quickly, improving patient compliance and the economics of drug treatment, both of which represent increased clinical value.
In addition, the high-end formulations selected by Luye Pharma are difficult to copy and are basically exclusive products. The market itself is very large and the company can expect reasonable returns. Therefore, we must identify the commercial positioning; identify unmet clinical needs to develop differentiated products that have a large potential market and little competition. This ensures that the products achieve commercial value and bring better benefits to patients, thus it is Luye Pharma’s R&D strategy.
Q: What is the future potential of the new products?
A: The changes to the original drugs can be represented as changes to A, D, M and E, meaning absorption, distribution, metabolism, and excretion, and their development is not isolated. From the formulations and pills in the field of traditional Chinese medicine to capsules and injections in the field of chemical drugs, to liposomes, long-acting extended-release microspheres and other complex preparations, as well as new biological products, the development of drug products evolves as new drugs are discovered and developed.
Let’s take the hypoglycemic agent GLP-1 (glucagon-like peptide-1) as an example. GLP-1 is a relatively large polypeptide, which was administered once a day by injection, and then extended to once a week by injection. Now it has been improved into an oral preparation, providing a minimally invasive and convenient treatment option for controlling blood sugar. To date, no other polypeptide has been administered orally. It can be said that this is a big step forward in the field of peptides.
The application of preparations in biological antibodies is also promising. Ranibizumab, a product developed by Roche for the treatment of fundus macular degeneration, is a classic example. Initially, the injection frequency of this product was once a month, and the clinical effect was good.
However, the total number of injections a human eyeball can handle is limited, generally around 10 or so injections, meaning that patients have to stop after around one and a half years of treatment. However, Roche has not stopped on the road of technical iteration. Currently, an upgraded version of this drug is being developed. The Port Delivery System, which is injected into the vitreous, is coated with ranibizumab and requires only one injection every 6 months. It is currently in Phase III clinical trials. If the clinical trial is successful, this new product will represent another big breakthrough made in this treatment area.
In addition, new formulations can be used for more advanced cell therapy and gene therapy. In gene therapy, a virus used as a vector, while in cell therapy, the gene can be transferred to a cell and the cell is used as a carrier. This has also allowed new formulations to continue to expand and evolve. The development of new drugs, especially those with high technical barriers, is promising, and will continue to be one of the core areas for Luye Pharma in the future. Luye’s strategic plan is to extend the research from small molecules to antibodies, and further to the treatment of disease causes.
The development of new drugs cannot be done for the sake of novelty in itself, thus ignoring clinical needs. Innovation is only a means to an end, and the ultimate purpose is to address unmet clinical needs, including efficacy, compliance, and side effects. Therefore, whether a new molecular compound or a modified new drug, it can only be regarded as true innovation when it can address clinical pain points.