Three Key Updates: Qilu Pharma's Pomalidomide Launch Outpaces Originator; Eli Lilly Expands Tirzepatide into New Indication; BMS Halts Phase III Radiopharmaceutical Trial Due to Supply Shortage

A total of 3 briefs | Reading time approximately 3 minutes◆◆ ◆

01

Qilu Pharmaceutical's Generic Pomalidomide Launch Outperforms Original Research

The market battle for Pomalidomide Capsules, a blockbuster potential product, has already begun.

Recently, according to the official website of the National Medical Products Administration, Qilu Pharmaceutical's anti-tumor drug Pomalidomide Capsules has officially received marketing approval.

Pomalidomide (Pomalyst/Imnovid) is a thalidomide analog developed by Celgene, a subsidiary of Bristol-Myers Squibb (BMS), and belongs to the class of immunomodulatory drugs. The original drug was developed by Celgene and received FDA approval in February 2013, with European approval following in August of the same year. However, the drug did not enter the Chinese market immediately.

In fact, the pomalidomide capsule is a typical case where a generic drug was approved for marketing before the original drug. In the Chinese market, the first company to launch the product was Chia Tai Tianqing, which received approval for the first generic version in November 2020. In June 2022, the original developer, Bristol-Myers Squibb (Celgene), also submitted an application for the marketing of pomalidomide capsules. In the coming years, as one of the popular generic drugs for multiple myeloma, the market competition for pomalidomide will become increasingly intense.

Securing Over 3 Billion in Major Varieties, Qilu Becomes the Second Chinese Manufacturer

Multiple Myeloma (MM) is a malignant disease characterized by the clonal proliferation of abnormal plasma cells and is one of the most common malignant tumors of the hematological system. Currently, the incidence of multiple myeloma in China has surpassed that of acute leukemia, making it the second most common malignant tumor of the hematological system.

In recent years, with the rapid development of pharmaceutical technology, pomalidomide, as the third-generation immunomodulatory drug following the first-generation thalidomide and second-generation lenalidomide, has demonstrated unique effects in anti-infection, immune modulation, anti-tumor proliferation, and anti-tumor angiogenesis. It has also shown its unique value in the treatment of multiple myeloma, particularly demonstrating good efficacy and lower toxicity in clinical trials for refractory and relapsed multiple myeloma.

Clinical data show that pomalidomide has a high remission rate in the treatment of newly diagnosed relapsed/refractory multiple myeloma, and can significantly prolong progression-free survival and overall survival during subsequent maintenance and consolidation therapy. Pomalidomide also demonstrates convincing efficacy in patients refractory to both lenalidomide and bortezomib.

In February 2013, pomalidomide was first approved by the FDA for the treatment of multiple myeloma patients who have received at least two prior therapies, including lenalidomide and proteasome inhibitors, and have demonstrated disease progression during or within 60 days after their last therapy. In August of the same year, this indication was approved in the EU. In May 2020, pomalidomide expanded its indications in the United States to include the treatment of Kaposi's sarcoma, becoming the first oral medication for this disease.

Since its launch, the sales of Pomalidomide have continued to grow. It rapidly increased from US$305 million in 2013 to US$2.04 billion in 2018, breaking through the US$2 billion mark for the first time and bringing significant profits to BMS.

According to BMS financial report, the global sales of Pomalidomide in 2023 were $3.441 billion. Meanwhile, data from MiNe Network shows that the sales of Pomalidomide capsules in Chinese public medical institutions, including urban public hospitals, county-level public hospitals, urban community health centers, and township health centers (referred to as Chinese public medical institutions), reached nearly 200 million yuan in 2023, representing a year-on-year increase of 44.02%.

It is worth mentioning that pomalidomide's "brother" – lenalidomide, a second-generation drug for multiple myeloma (MM) – has grown into a multi-billion-dollar product, and is currently one of the best-selling drugs globally. In 2021, it ranked 2nd in the list of the world’s top-selling oncology drugs with sales reaching $12.82 billion, second only to Keytruda (K药). Currently, pomalidomide is generally used as a supplementary treatment to lenalidomide, mainly applicable in cases where lenalidomide is ineffective or resistance has developed. Additionally, the breadth of indications for pomalidomide still needs further development.

Qilu Pharmaceutical initiated the development of Pomalidomide Capsules in 2013, submitted a new drug application on August 16, 2022, and received acceptance from the CDE. The approved Pomalidomide Capsules cover four clinical specifications. Compared with existing pomalidomide capsules in China, two new specifications, 2mg and 3mg, have been added, making it more suitable for patients with mild to severe hepatic and renal impairment, allowing for more convenient dose adjustments.

At the same time, according to a national population analysis study, from 2012 to 2016, the prevalence and incidence of MM in China were 5.68/100,000 and 1.60/100,000 people respectively, indicating a significant clinical demand for pomalidomide in China. Despite the availability of one domestically produced pomalidomide product in the market, there remain numerous unmet needs in clinical practice and the market.

Generic Drug Development Preparation: Seizing the Rapid Growth Phase

According to the CDE official website, multiple companies in China have already entered the pomalidomide capsule market.

Chia Tai Tianqing Pharmaceutical Group Co., Ltd. was the first to submit the marketing application for Pomalidomide Capsules in July 2018, with specifications of 1mg and 4mg. In October of the same year, it was included in the priority review process, and in November 2020, it obtained the first generic approval and became the first to pass the evaluation.

It is worth mentioning that Pomalidomide Capsules successfully entered the National Reimbursement Drug List (NRDL) in the 2021 reimbursement negotiations and also successfully renewed in the 2023 version of the National Reimbursement Drug List (Category B).

Data from Menet shows that after CHIATAI TIANQING's pomalidomide capsules were included in the medical insurance, they experienced a significant sales increase. In 2022, the product's sales in Chinese public medical institutions (including urban public hospitals, county-level public hospitals, urban community health centers, and township health centers) exceeded 130 million yuan, with a growth rate of 648.30%. In terms of sales channels, urban public hospitals accounted for over 80%, while county-level public hospitals accounted for approximately 15%.

In 2020, Yangtze River Pharmaceutical's submitted Category 3 generic drug — Pomalidomide Capsules received two clinical implied licenses. The indications are: to be used in combination with dexamethasone for the treatment of adult patients with multiple myeloma who have previously received at least two therapies (including lenalidomide and bortezomib) and have demonstrated disease progression or completed their last treatment within 60 days.

In addition, in the development and preparation of generic drugs by local pharmaceutical companies in China, companies that have registered for the imitation of varieties include Jiangsu Hengsen Pharmaceutical, Jiangsu Simcere Pharmaceutical, Jiangsu Aosaikang Pharmaceutical, Nanjing Huaweiyi Pharmaceutical, Nanjing Cavendish Bio, Hefei Jiunuo Pharmaceutical, Hebei Guolong Pharmaceutical, Shijiazhuang Siyao, Hefei Xinfeng Technology, Jiangsu Jiayi Pharmaceutical, Beijing Furui Kangzheng Pharmaceutical, Beijing Kelai Bo Pharmaceutical, Hangzhou Heze Pharmaceutical, Dafeng Disinovo Pharmaceutical, Shanghai Innovation Pharmaceutical, and Qilu Annti Pharmaceutical, etc.

According to statistics, there were approximately 176,000 new cases of MM globally in 2020, accounting for 1% of all new cancer cases worldwide. Additionally, according to Frost & Sullivan and Kantar Health, the number of MM patients in the four major markets—the United States, China, the five European countries, and Japan—was approximately 148,000, 126,000, 122,000, and 28,000, respectively, in 2021.

With the population growth and aging trend, coupled with the application of earlier effective treatments and new drugs, patients' survival time has significantly extended. China will become the country with the fastest-growing number of patients in the next decade, with an annual compound growth rate as high as 8%. By 2030, the number of patients is expected to increase to 266,000, making it the largest MM patient market globally.

It is estimated that, starting from 2017, the MM market in eight major countries globally (the United States, the European G5, China, and Japan; 8MM = 8 major markets) has approached nearly 15 billion US dollars and is projected to grow at a compound annual growth rate (CAGR) of 6.7%, reaching 27.8 billion US dollars by 2027. Among these, the Chinese MM market will increase from 670 million US dollars in 2017 to 4.14 billion US dollars in 2027, with a high compound annual growth rate of 20.3%.

From the perspective of clinical indication development, indications such as myelofibrosis, brain cancer, and scleroderma have entered clinical development. If approved in the future, it will bring greater benefits to the market expansion of pomalidomide. In terms of registration and application of products in China, pomalidomide has received high favor, with nearly 20 companies having developed generic versions of this product. The competition for the domestic market in China has already begun, and it is believed that the future domestic market for this product will show a certain degree of positive performance.

(Source: Pharmaceutical Economy News)

02

Eli Lilly's Tirzepatide Expands into New Arena

The GLP-1 field, as the "top stream" in the pharmaceutical market, attracts the attention of the industry with every move.

Recently, at the annual meeting of the European Association for the Study of the Liver (EASL), Eli Lilly and Company announced positive data from the Phase 2 clinical trial, SYNERGY-NASH, of its GLP-1 class drug Tirzepatide in treating patients with Metabolic Dysfunction-Associated Steatohepatitis (MASH).

These data not only bring hope to MASH, a disease that currently has no FDA-approved treatment, but also significantly boost market confidence in Eli Lilly and Company. Driven by this positive news, the stock price of Eli Lilly surged substantially this week, breaking through the 800 billion US dollar market capitalization mark and hitting a record high of 849.99 US dollars per share.

The significant rise in stock price reflects investors' optimistic expectations for Eli Lilly's future development prospects.

Market analysts generally believe that if tirzepatide can continue to maintain such efficacy in subsequent clinical trials and ultimately gain FDA approval, it will become a new revenue growth point for Eli Lilly, further solidifying its leadership position in the pharmaceutical industry. At the same time, it will also drive competition and development within the industry, pushing other companies to accelerate their R&D efforts and improve the efficacy and safety of their own products in order to secure a place in the market.

Does Tirzepatide Cross Over to MASH?

Metabolic Dysfunction-Associated Steatohepatitis (MASH) is a severe chronic liver disease that represents a progressive form of nonalcoholic fatty liver disease (NAFLD). MASH is characterized by abnormal accumulation of fat in the liver, accompanied by inflammation and hepatocyte injury, which may lead to further fibrosis, cirrhosis, and even liver cancer.

MASH is usually closely associated with metabolic syndrome, including conditions such as obesity, hypertension, diabetes, and dyslipidemia. Approximately 5% of adults worldwide are affected by MASH, and in regions with higher prevalence rates of metabolic syndrome, such as obesity and type 2 diabetes, the incidence of MASH may be even higher.

Frost & Sullivan data shows that by 2030, the global NAFLD population is expected to reach 2.43 billion, with the number of MASH patients reaching 490 million. The global market size for NASH drugs is projected to exceed $30 billion. This forecast has injected confidence into global pharmaceutical companies, prompting them to increase their R&D efforts in the MASH field.

Due to the complex and not yet fully understood pathogenesis of MASH, pharmaceutical companies worldwide are conducting in-depth explorations from multiple potential therapeutic directions. In March this year, Madrigal's thyroid hormone receptor β (THR-β) agonist Resmetirom took the lead, becoming the frontrunner in the market. Meanwhile, GLP-1-based drugs, known as the "cross-disciplinary wonder drug," have emerged as a surprising "dark horse," demonstrating remarkable potential in the MASH treatment field.

As a GLP-1/GIP dual receptor agonist, tirzepatide was initially approved by the U.S. Food and Drug Administration (FDA) in May 2022 for the treatment of type 2 diabetes under the brand name Mounjaro. Subsequently, in November 2023, tirzepatide received FDA approval for weight management under the brand name Zepbound.

Against this backdrop, the clinical research on tirzepatide has not stopped.

SYNERGY-NASH is a randomized, double-blind, and placebo-controlled study evaluating the efficacy and safety of tirzepatide in patients with histologically confirmed NASH and stage 2 or 3 fibrosis.

The study enrolled a total of 190 patients who were biopsy-proven to have MASH, with fibrosis stages F2 or F3 and a Nonalcoholic Fatty Liver Activity Score (NAS) ≥4. They were randomly assigned in a 1:1:1:1 ratio to receive once-weekly subcutaneous injections of tirzepatide (5mg, 10mg, or 15mg) or placebo for 52 weeks.

The results showed that, without MASH deterioration, the proportion of patients with fibrosis improvement ≥1 stage in each group was: 29.7% in the placebo group, 54.9% in the 5mg group, 51.3% in the 10mg group, and 51.0% in the 15mg group (p<0.05). Additionally, 71.7% to 78.3% of patients in the three dose groups had a NAS score reduction of ≥2 points, compared to 36.7% in the placebo group.

The versatility of Tirzepatide has attracted widespread attention in the medical field, bringing new exploration paths and market prospects to the pharmaceutical industry. Industry opinions suggest that with the continuous advancement of clinical research, GLP-1 drugs are expected to become a new treatment option for MASH, offering new hope to patients.

MASH Ignites the "Golden Track"?

The positive results achieved in the SYNERGY-NASH clinical trial not only added new luster to tirzepatide but also brought certain market competition pressure to Madrigal company and its main product Resmetirom.

On the morning of June 5th, Madrigal's stock price plummeted significantly during early trading, reflecting investors' concerns about this new competitive landscape. Although Resmetirom, as the first MASH treatment drug approved by the FDA, holds a first-mover advantage in the market, the impressive clinical trial results of tirzepatide may alter the future market dynamics.

The large patient population and the scarcity of treatment drugs have made MASH a golden track with significant growth potential in the eyes of many pharmaceutical companies.

To date, more than a hundred potential therapeutic targets for MASH are being actively developed or have entered clinical trial stages. These targets cover a variety of different biological pathways and mechanisms, including but not limited to THR-β agonists, GLP-1 receptor agonists, fibroblast growth factor 21 (FGF21) analogs, and peptide-based GLP-1/GCGR dual receptor agonists.

In addition to Resmetirom and Tirzepatide, the main products for MASH indications in the late stage of development are:

Novo Nordisk's Semaglutide: As a GLP-1 receptor agonist, semaglutide was originally used to treat type 2 diabetes, but studies have shown that it demonstrates potential therapeutic effects in reducing liver fat content and improving liver fibrosis. The ongoing Phase III clinical trial aims to evaluate its efficacy and safety in patients with MASH.

Akero Therapeutics' Efruxifermin (EFX): As an FGF21 analog, Efruxifermin is currently being evaluated in Phase III clinical trials. FGF21 is a protein with liver-protective, metabolic-regulating, and anti-inflammatory effects. By mimicking the action of this natural hormone, Efruxifermin may help improve liver health in patients with MASH.

Inventiva's Lanifibranor: This is a PPAR agonist. Although patient recruitment was suspended in Phase III clinical trials due to safety concerns, it showed potential to improve liver fibrosis in MASH patients in earlier studies.

The development of Chinese pharmaceutical companies in the MASH field is remarkable. Gannex Pharma's ASC41 showed a significant reduction in liver fat content in a 52-week interim study, demonstrating good efficacy and safety. In addition, domestic companies such as Zhenzhu Pharma, CHIATAI TIANQING, Gannex Pharma, Yakreation Pharma, and Terns Biopharmaceuticals are actively making progress, with some products already entering the clinical trial stage.

Despite the challenges in the development of MASH drugs, the field of MASH treatment is gradually seeing progress as our understanding of disease mechanisms deepens and treatment methods continue to innovate. The positive results achieved by tirzepatide in the SYNERGY-NASH clinical trial have further heightened market expectations for MASH therapeutic drugs.

Competition between companies will not only accelerate the R&D process of new drugs but also potentially lead to more personalized and precise treatment options. With the completion of more clinical trials and the approval of new drugs, it is expected that the field of MASH treatment will witness more breakthroughs and choices in the coming years.

(Source: Pharmaceutical Economy News)

03

BMS Nuclear Medicine Phase III Halted Due to Supply Shortage

On June 4, 2024, Bristol-Myers Squibb (hereinafter referred to as BMS) announced that it has currently suspended the recruitment of new patients for the Phase 3 trial of the radiopharmaceutical RYZ101. After confirming via email with a spokesperson from radiopharmaceutical developer RayzeBio, it was revealed that the suspension was due to a shortage in the supply of actinium-225, the α-particle radionuclide selected for RYZ101.

Occasionally, the development of nuclear medicine has to be put on hold due to supply constraints, a situation that has become an industry-wide consensus. However, BMS, being in the seemingly ever-booming hotspot track of nuclear medicine, had no choice but to personally experience this by halting its Phase 3 clinical trial.

After all, not long ago, BMS made a significant acquisition of RayzeBio, a rising star in nuclear medicine, at a premium of approximately 250%, with a total cost of $4.1 billion. For BMS, whose oncology business was in dire need of revitalization at the time, this was both a bold move to expand its business segment and a high-stakes gamble to revive its performance.

Radiopharmaceutical Supernova: Sold for $4.1 Billion Three Years After Establishment

On December 26, 2023, BMS and RayzeBio announced that they had reached a definitive merger agreement. Under the agreement, BMS will acquire RayzeBio for $62.50 per share in cash, with an equity value of approximately $4.1 billion. The transaction was unanimously approved by the boards of directors of both BMS and RayzeBio.

The story of RayzeBio, the supernova in nuclear medicine, has been celebrated in the industry: founded in 2020, with only three products in its pipeline, it successfully completed four rounds of financing within three years, raising a total of $418 million. Also within those three years, RayzeBio went public against the backdrop of a cooling capital market in 2023, successfully raising $311 million and becoming the second-largest IPO in the U.S. biotech sector that year. Not only that, but just over three months after its IPO, RayzeBio was acquired by BMS for $4.1 billion at a 250% premium.

Calling RayzeBio a "pig in the wind" seems unfair.

RayzeBio's novel proprietary peptide RYZ801, targeting glypican-3 (GPC3), is currently under IND investigation for actinium-based radiotherapy to treat hepatocellular carcinoma. Additionally, the pipeline targeting CA9 has also entered the IND stage.

The most notable candidate in RayzeBio's potential BIC pipeline is RYZ101. RYZ101 is a radiopharmaceutical conjugate (RDC) that targets somatostatin receptor 2 (SSTR). The key difference between this drug and most current nuclear medicines lies in the radionuclide it uses.

Radionuclides, or radioactive isotopes, refer to metal or non-metal elements that can emit α, β, or γ radiation. These radionuclides decay and emit radioactive rays, which damage chromosomes in cells, halt their growth, and thereby destroy proliferating cancer cells. Currently, the radionuclides used in the RDC field are mainly β-emitting radionuclides, such as Novartis' star radiopharmaceutical Lutathera, which utilizes a β-emitting radioactive isotope.

RYZ101, on the other hand, uses the alpha-particle emitting isotope actinium-225 as its radionuclide. Compared to beta particles, alpha particles deliver 400 times more energy, causing more frequent double-strand DNA breaks and thereby killing tumor cells. Theoretically, RYZ101 has the potential to be more effective than radiopharmaceuticals that use beta-emitting radionuclides.

RYZ101 is advancing into Phase 3 clinical trials for the treatment of gastroenteropancreatic neuroendocrine tumors (GEP-NETs), as well as early development stages for the treatment of small cell lung cancer and other potential tumors. Whether considering the progress of its research and development or its therapeutic potential, RYZ101 has the possibility to become a new therapy in the field of GEP-NETs; if successful, it may pave a new path for the development of nuclear medicine.

BMS is precisely focused on this point.

It is worth mentioning that, in addition to RayzeBio's clinical prospects, BMS has also expressed interest in RayzeBio's upcoming factory in Indianapolis, which is expected to cover approximately 60 million square meters. Previously, RayzeBio stated on its official website that it was gradually building the capability to produce Actinium-225 at this facility.

It can be said that, from the outset of the acquisition, BMS incorporated the improvement of the nuclear medicine supply chain into its future business planning considerations, but still could not escape the predicament of isotope shortages.

Actinium-225 Supply: A Critical Step Behind Schedule, Accelerated Production Too Late

When discussing the various challenges in innovative drug development, the difficulty of radiopharmaceutical R&D is singled out due to its unique characteristics. Supply chain, selection of appropriate isotopes, drug efficacy, and logistics during transportation are all difficulties that need to be overcome, especially for a Biotech company, particularly startups. Among these, the supply chain is one of the key factors affecting radiopharmaceutical sales. Unlike ordinary drugs that can be stored for a long time, the half-life of radionuclides in radiopharmaceuticals is extremely short, resulting in a shelf life of only a few days. This requires pharmaceutical companies to have not only production capabilities but also distribution capabilities.

Novartis, which invested heavily in nuclear medicine pipelines earlier than BMS, is also facing the same issues earlier than BMS.

In March 2022, Novartis' Pluvicto received FDA approval for third-line treatment of PSMA-positive metastatic castration-resistant prostate cancer, becoming the world's first PSMA-targeted radioligand therapy. In the first quarter of 2023, despite extremely tight supply, Pluvicto's sales still reached $211 million, a year-on-year increase of 18%, surpassing Wall Street's expectation of 11%. In the second quarter of the same year, Pluvicto continued to gain momentum, with sales reaching $240 million. This brought the total sales of Pluvicto in the first half of the year to $450 million. Industry experts believe that, barring any unforeseen circumstances, Pluvicto's sales in 2023 will easily exceed $1 billion, thereby joining the ranks of blockbuster drugs.

Pluvicto's actual sales in 2023 were $980 million. Despite the impressive figure, its full potential was not realized, with supply being the limiting factor.

Due to the huge demand, Pluvicto's production capacity has been insufficient due to a shortage of isotope supply, resulting in a significant clinical demand gap. Additionally, the drug has a shelf life of only a few days and cannot be stockpiled in advance, limiting the widespread use of Pluvicto. This has forced Novartis to suspend patient recruitment. In cases where all chemotherapy options have failed, patients who should have had a lifeline of hope are now left waiting for months, at the mercy of luck.

BMS's valued RYZ101 utilizes the radionuclide actinium-225, which has a half-life of 10 days and is extremely rare in nature, requiring artificial synthesis. Internationally, the actinium-225 isotope used for clinical research or drug synthesis is primarily produced through the decay of thorium-229. The annual production is less than 2.5 curies, and it once reached a price extreme of 1 million USD/mCi (millicuries), being dubbed "the rarest drug on Earth."

Despite multiple countries joining the competition for mass production of Actinium-225, due to BMS's insufficient control over the production progress of Actinium-225 in the early stage, the factory built by RayzeBio in Indianapolis in 2023 for the mass production of Actinium-225 radionuclides and radiopharmaceutical preparations has not been fully put into use until now. The consequence of being "one critical step" behind is the suspension of the Phase 3 clinical trial of RYZ101, which is forced to replay a scene no different from its competitor Novartis.

Novartis' wake-up call didn't alarm its competitor BMS, but it provided AstraZeneca with a solution.

In March 2024, AstraZeneca announced the acquisition of Fusion Pharmaceuticals (hereinafter referred to as Fusion), with a transaction value of $2.4 billion.

Fusion is also coincidentally conducting a Phase 2 study on actinide therapy for prostate cancer. Fusion's most advanced R&D project at present is FPI-2265, a prostate-specific membrane antigen (PSMA)-targeted radiopharmaceutical therapy, which is currently in Phase 2 clinical trials as a treatment for metastatic castration-resistant prostate cancer (mCRPC). The radionuclide delivered by FPI-2265 is actinium-225.

Although Fusion's brilliance may not match that of RayzeBio, its Actinium-225 production facility has been fully operational since January 2024. This means that AstraZeneca won’t have to worry about potential disruptions to Phase II clinical trials after acquiring Fusion, paving the way for a smoother path toward commercialization.

Global Isotope Mass Production Accelerates

The road to mass production of Actinium-225 is risky and long, with many countries joining the capacity competition.

In 2021, Canadian Nuclear Laboratories (CNL) and ITM Isotope Technologies Munich SE signed a Memorandum of Cooperation to jointly advance the research, development, and industrial application of Actinium-225 production technology. In 2023, Canadian Nuclear Laboratories also reached an agreement with the Saskatchewan Centre for Nuclear Innovation to further boost the production of Actinium-225 by more than 30 times.

In 2022, Kebesova, Deputy General Manager of Rusatom Healthcare, stated that Rosatom is prepared to begin construction of the largest radiopharmaceutical production plant in Europe in Obninsk. The plant is scheduled to commence commercial operations as early as 2025, with construction costs estimated at approximately 9 billion rubles and an annual production capacity of 89,000 curies. It will produce commonly used radiopharmaceuticals (such as iodine-131, samarium-153, and molybdenum-99), as well as certain promising radiopharmaceuticals (such as lutetium-177, actinium-225, and radium-223).

In China, at the beginning of 2024, a research team led by Qin Zhi, a researcher from the Nuclear Chemistry Laboratory of the Institute of Modern Physics, Chinese Academy of Sciences, used the beam provided by the Lanzhou Heavy Ion Accelerator Research Facility (HIRFL) to bombard a metallic thorium target. They prepared the medical isotope actinium-225 using an independently developed automated separation device. The related achievements have applied for and been granted an invention patent titled "An Automated Processing Device for Separating Actinium-225 and Its Operation Method."

It is reported that Qin Zhi's team used the beam provided by HIRFL to bombard a metallic thorium target, establishing the chemical separation and purification process for the medical isotope actinium-225. By employing an independently designed and processed automated separation system, they achieved efficient, repeatable, and batch-oriented separation and purification of the medical isotope actinium-225, avoiding the tedious manual operations and the potential risks posed by high-dose radiation to operators. This breakthrough is expected to change the situation where all actinium-225 in China relies on imports.

Companies also enter the commercial production market of Actinium-225.

NorthStar Medical Radioisotopes commenced commercial production of the therapeutic radioisotope Actinium-225 in the United States in 2023. A customized IBA Rhodotron TT 300-HE electron beam accelerator has been delivered to NorthStar's new Ac-225 production facility in Beloit, Wisconsin. This facility will be dedicated to producing no-carrier-added Actinium-225.

Founded in 2023 and located in Guangdong Province, Panmedic Holdings (Shenzhen) Co., Ltd., led by two British academicians and in collaboration with Tsinghua Nuclear Research Institute, focuses on the research, production, and sales of "the rarest drug on Earth," Ac-225, aiming to overcome the dual bottlenecks of technology and capacity that China has long relied on imports for.

Back to BMS, the remedial measures taken by this multinational giant cannot change the fact that patient recruitment for the Phase 3 trial of RYZ101 has been suspended. However, its existing actions may reduce some obstacles for RYZ101 in its subsequent commercialization process. In March 2024, Ratio, a nuclear medicine company supported by BMS, expanded its manufacturing agreement with CDMO PharmaLogic to ensure a commercial GMP-grade supply chain as much as possible.

In addition, RayzeBio's spokesperson repeatedly emphasized that all patients currently participating in ACTION-1 will continue to receive treatment, with plans to resume recruitment of new patients in the third quarter.

(Source: Arterial New Medicine)