Author: HE Sheng

Endocrine therapy is a first-line therapy for prostate cancer, with gonadotropin-releasing hormones (GnRH) occupying a strong position. Although the incidence of prostate cancer in China is much lower than that in the United States, with life expectancy on the rise the incidence of prostate cancer is increasing as well. Prostate cancer is the most common non-skin cancer and the second leading cause of cancer deaths in men in the United States. According to statistics from the National Cancer Institute, there were more than 170,000 newly diagnosed prostate cancer patients in 2019, and about 30,000 died of prostate cancer.

Among the three major Chinese GnRHa available, goserelin hormone therapies occupy the largest portion of the market. However, due to current limitations, the ultra-long-acting injections produced on other countries, where one injection occurs in March and one injection occurs in June, have not yet been successfully developed. Thus, the hormone therapies currently on market in China have limits to their application in the palliative treatment of prostate cancer.

Foresee Pharmaceuticals and GeneScience reach an agreement

Recently, Changchun High & New Tech Industry Inc announced that its subsidiary GeneScience Pharmaceuticals has reached an exclusive licensing agreement with Foresee Pharmaceuticals in Taiwan to obtain the commercialization of Foresee’s novel FP-001 program, Leuprolide Mesylate Injectable Suspension (LMIS) ready-to-use subcutaneous 6-month and 3-month depot formulations (“Camcevi™”). The rights include the development, sales, technology transfer, manufacturing after technology transfer, and global non-exclusive manufacturing and supply of the product.

According to the disclosed aggrement, Foresee can receive up to US$123.85 million in total, including an upfront payment of US$8 million, R&D and regulatory milestone payments, technology transfer milestone payments, sales milestone payments, and royalty payments, along with sales profit share in the authorized market.

Foresee Pharmaceuticals had previously submitted an NDA to the US FDA for their Camcevi™ formulations to treat prostate cancer.

LMIS is a long-acting sustained-release peptide injection. The results of international multi-center phase III clinical trials of its specification (50 mg) for the treatment of prostate cancer were announced in January 2017. The results showed that up to 97% of the subjects reached the main efficacy indicators. The results of the 25 mg international multi-center clinical phase III trials were announced in February 2019. The results showed that up to 97.9% of subjects reached the main efficacy indicators. The safety data of FP-001 50mg 6-month depot formulations was also similar to that of comparable drugs on the market.

▲Foresee Pharmaceutical R&D pipeline

Product details

At present, on-market products separate the particulate carrier and the active ingredient into two injection syringes, resulting in a complicated design. Additionally, a complicated mixing step is required before injection. This may cause inaccurate dosage and result in microsomes blocking the needle.

The “SIF sustained-release drug delivery technology” significantly improves the stability of the dosage form. FP-001 50mg can not only be pre-filled in the ready-made monomer syringe, but also has a satisfactory storage shelf life. In other words, Foresee’s self-developed SIF sustained-release injection technology has successfully overcome the technical barriers to preserve and use highly active leuprolide injections that had been in place for about 30 years.

FP-001 50mg is more convenient to use than its competitors, does not need to be mixed before use, and will not cause needle blockage. This product has low manufacturing cost, is convenient to use, high acceptance by clinicians, high patient compliance and remarkable treatment effect.

Market performance comparison of similar products

Gonadotropin-releasing hormone (GnRH) is secreted by the hypothalamus. According to the NIH National Cancer Institute, GnRH “causes the pituitary gland in the brain to make and secrete the hormones luteinizing hormone (LH) and follicle-stimulating hormone (FSH). In men, these hormones cause the testicles to make testosterone. In women, they cause the ovaries to make estrogen and progesterone.”

The three commonly used leuprolides in China are leuprolide, goserelin, and triptorelin. All have a huge market. Among them, leuprolide is the most common type of drug and fastest-growing one for treatment of prostate cancer in China.

In the 1980s, leuprolide was first marketed in Europe, and in the United States in 1989 for precocious (early onset) puberty. Leuprolide entered the Chinese market in 1996. According to Michigan Medicine at the University of Michigan, “leuprolide is used in men to treat the symptoms of prostate cancer (but does not treat the cancer itself). Leuprolide is used in women to treat symptoms of endometriosis (overgrowth of uterine lining outside of the uterus) or uterine fibroids.”

According to IMS data, the total global GnRHa sales in 2019 was US$4.29 billion, with a 7-year compound growth rate of only 2.14%. The market has stabilized, and only the Chinese market is still growing rapidly. Among many GnRHa, leuprolide is the most popular, with total sales of US$2.75 billion in 2019 and a compound growth rate of 2.84% over the past seven years.

In China, the total national sales in 2019 was RMB 6.13 billion, with a compound growth rate of 17.54% over the past seven years. The market is growing rapidly. Compared with the global market, China’s GnRHa market is more concentrated, with sales primarily coming from leuprolide, goserelin, and triptorelin, accounting for 44.44%, 39.19% and 16.36% of total sales respectively. In terms of dosage form, leuprorelin sales almost all come from microspheres.

Microsphere preparations have very high technical barriers, due to them being of different particle sizes, involving high cost and difficulty, and because it is difficult to ensure stable and reliable product quality. The biggest challenge lies in how to achieve industrialization. Because microsphere preparations are difficult to scale-up production linearly, it is necessary to explore suitable parameters to achieve stable scale-up production of microsphere preparations. Technical requirements for making the drug are high.

Due to these high technical barriers, the microsphere field naturally has higher barriers and a better competition pattern. Competition is not particularly intense, the price pressure is small, and the market potential is large. At present, the only microsphere preparations on the market in China are leuprolide microspheres from Livzon and Bont.

In 2013, the drug market of leuprorelin in sample hospitals in 16 key cities in China were Takeda’s “Yinatong”, Beijing Biote Pharmaceutical’s “Bo’enuokang” and Livzon’s “Beiyi”. Each accounted for 58.66%, 23.03% and 18.31% of the market respectively.

Summary

Long-acting sustained-release formulation can effectively reduce medical costs, increase patient compliance, and save doctors and patients’ time. At present, the longest sustained-release period of products related to leuprorelin long-acting sustained-release preparations on the Chinese market is only 3 months. Now there is the new leuprorelin mesylate product by GeneScience and Foresee, which has the highest sustained-release period of up to 6 months. The collaboration reached should help fill industry gaps.

In the Chinese market, currently there are few types of microspheres approved for listing. Due to factors such as technology and capital, the microsphere market is far from being opened in China. At the same time, long-acting injections have high technical barriers, low market competition pressure, and very substantial profits. They represent a good potential investment area.

References

GeneScience Pharmaceuticals official website

Foresee Pharmaceuticals official website