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The global nuclear medicine map is quietly changing.
Recently, Novartis announced its 2023 results, with annual net sales of 454$400 million, up 10% year-over-year, core operating income up 18%, net income of $8.6 billion.
It is worth noting that Novartis' 2 nuclear drugsLutathera and Pluvicto's total sales in 2023 will exceed US$1.5 billion (equivalent to 11.4 billion yuan)., Novartis became one of the first companies to "eat crabs".
Tens of billions of nuclear drug catchers are a blockbuster, how does Novartis take down the hard bones?
Won 11.4 billion,
Novartis is leading the nuclear drug frenzy
Nuclear drugs are mainly divided into:Radiopharmaceuticals for diagnosis and radiopharmaceuticals for **There are two main categories, **class radiopharmaceuticals, which can selectively and target diseased tissues through nuclides**.
In the early years of development, radiopharmaceuticals have been mainly developed and used as important cancer diagnostic drugsDiagnostic nuclear drugs account for more than 80% of the marketNuclear drugs are limited by upstream nuclide production capacity, as well as relatively strict approval processes and conditions of useOnly 166%
At present, radionuclide drug conjugates (RDCs) in the nuclear medicine subdivision track have become a hot spot in R&D.
Novartis is the king of RDC, and since 2016, 11 RDC drugs have been approved for marketing in the world, of which 5 drugs are Novartis products, and Novartis' Lutathera and Pluvicto are the only 2 RDC drugs used for **
Lutathera was approved by the FDA on January 26, 2018 for the treatment of patients with gastroenteropancreatic neuroendocrine tumors with somatostatin receptor (SSTR).
Lutathera achieved sales of 1$6.7 billion, which grew to $4 in 2019$4.1 billion, with 2022 revenue of 4$7.1 billionIn 2023, sales increased to 60.5 billion US dollars
Pluvicto has shown a stronger sales explosion than Lutathera, achieving 2$700 million in salesIn 2023, the total sales will reach 9US$800 million, a year-on-year increase of 261%.(Figure 1) [2].
Figure 1 Sales of Pluvicto.
Novartis 2023 financial report.
Pluvicto was approved by the FDA on March 23, 2022 for patients with PSMA-positive MCRPC (castration-resistant prostate cancer).It became the world's first radioligand targeting PSMA**.
The Pluvicto drug is the radionuclide LU-177, which has a number of advantages over traditional cancer methods: it minimizes the length of hospital stay; Good selectivity, only affecting pathological foci, but not healthy tissues; The active ingredient of the drug affects cancer cells in different locationsNot only against antigenic tumors, but also against metastatic cancer cells.
This has also enabled Pluvicto to achieve excellent results in clinical trials. In the Phase VISION clinical trial, the median overall survival using the Pluvicto+ criteria** was 15 in patients with MCRPC3 months, compared to 113 months, with a median overall survival prolonged by 4 months[3].
In October 2023, Novartis announced positive data from the Phase III PSMAFORE trial in Pluvicto: PSMAFORE met the primary endpoint of progression-free survival (RPFS) with an HR of 0411, compared to the control groupMedian RPFS more than doubled in the Pluvicto group to 12 months
In addition to Lutathera and Pluvicto, Novartis has two RDC drugs in Phase 1 clinical trials, 177-neob, 225ac-psma-r2, and 225ac-psma-617 (Fig. 2).
Figure 2 Novartis Phase 1 clinical pipeline in oncology.
Novartis 2023 financial report.
Pluvicto's outstanding sales have also prompted global pharmaceutical companies to join the layout of RDC drugs and grab this piece of the cake, such as Roche, Eli Lilly and BMS will successively acquire or cooperate to enter the nuclear medicine field in 2023.
More than nuclear medicine,
Hunt for breast cancer in an all-round way
Kisqali is a blockbuster drug in the field of Novartis oncology, which was approved for marketing in the United States and China in March 2017 and January 2023, respectively, in combination with aromatase inhibitorsFirst-line medications**For HR-positive and HER2-negative women with postmenopausal advanced metastatic breast cancer, Kisqali has received Breakthrough Designation and Priority Review Designation prior to approval.
As for nowIt is the only CDK4 6 inhibitor approved for advanced first-line premenopausal indications in China, Kisqali will provide a new option for premenopausal and perimenopausal HR+ HER2- advanced breast cancer patients in China, and bring hope for longer survival and better quality of life [5].
Previously, results from the monaleesa-2 trial in Kisqali showed a median follow-up of 6After 6 years, 334 patients in the Kisqali group (54.)2%), and 219 of 334 patients in the placebo group died (65.)6%）。
Compared with placebo plus letrozole, Kisqali plus letrozole showed a significant overall survival benefit. Median overall survival in the Kisqali plus letrozole group was 63At 9 months, 51 in the placebo plus letrozole group4 months,Survival benefit was more than 12 months
In December 2023, Novartis announced the results of an updated invasive disease-free survival (IDFS) analysis from Kisqali's Phase III Natalee trial: compared to standard endocrine alone**The combination of KISQALI adjuvant with nonsteroidal aromatase inhibitors** is associated with a reduced risk of disease** in patients with stage II and III HR+ HER2- early-stage breast cancer251%
Kisqali is the second CDK4 6 inhibitor marketed in addition to Pfizer's ibrance, with excellent efficacy and continuous approval of new indications, Kisqali sales are on the market year by year, with sales increasing by 75% year-on-year to 20 in 2023US$800 million, while the share of IBRANCE declined due to patent expiration and other CDK4 6 inhibitors such as Kisqali (Figure 3).
Figure 3 Sales of iBrance and Kisqali.
Pfizer, Novartis financial reports.
Siege self-exempt field,
BTK inhibitors "take the lead".
BTK inhibitors have achieved great success in the field of hematologic malignancies, especially ibrutinib, which reached 97 in 2021$800 million in peak sales.
Up to now, 6 BTK inhibitors for ** hematological tumors have been approved for marketing in the world, and many pharmaceutical companies are actively developing the application of BTK inhibitors in the field of autoimmunity.
However, the development of BTK inhibitors in the field of autoimmunity has not been smooth, and pharmaceutical giants have hit a wall one after another, but fortunately, Novartis' Remibrutinib has reached the primary endpoint of two phase 3 Remix-1 and Remix-2 in chronic spontaneous urticaria (CSU), giving BTK inhibitors a shot in the arm to enter the field of autoimmunity [8].
CSU is the medical term for chronic urticaria that lasts 6 weeks or more, and the root cause is internal rather than external exposure to any allergen. CSU affects 40 million people worldwide and is characterized by itchy hives (wheals) and/or swelling of deep tissues (angioedema), which can occur on the face, throat, hands, and feet. Patients may experience burning, tingling, and soreness on the ** where hives occur, which can seriously affect their quality of life.
H1-antihistamines are the first-line agent for CSU, yet approximately 60% of patients are not adequately controlled with antihistamines alone and continue to tolerate painful symptoms of CSU.
BTK inhibitors as an alternative to patients who do not respond well to antihistamines, RIf approved, emibrutinib could be the first new CSU in a decade.
Not only Remibrutinib has bravely entered the field of autoimmunity, many BTK inhibitors are exploring autoimmune diseases, such as Sanofi's two BTK inhibitors, Rilzabrutinib and Tolebrutinib, both of which are in phase 3 clinical trials for ** idiopathic thrombocytopenic purpura and multiple sclerosis, respectively (Table 1).
Table 1 Some BTK inhibitors under clinical development for ** autoimmune diseases.
Data**: Public information such as drug intelligence data and official websites of major companies.
Conclusion
In 2023, Novartis' business will be greatly adjusted, divesting the generic drug business, focusing on the field of innovative drugs, with clinical pipelines covering tumors, autoimmune fields, cardiovascular diseases, etc., seizing the opportunity of nuclear drugs and taking a leading position in the RDC field.
At the same time, Novartis also announced its guidance for 2024, with net sales expected to achieve mid-single-digit growth, core operating income expected to achieve high-single-digit growth, and net sales are expected to grow at a CAGR of 5%cc from 2023 to 2028 and 40% growth by 2027.
References. 1.BIG Bio Innovation Society: Nuclear Medicine: Past and Present, Market Size, Access Barriers, R&D Hotspots.
2.q4 2023 results investor presentation january 31,2024
3.fda approves pluvicto for metastatic castration-resistant prostate cancer
4.novartis pluvicto™shows clinically meaningful and highly statistically significant rpfs benefit in patients with psma-positive metastatic castration-resistant prostate cancer in the pre-taxane setting
5."Li" anti-pink killer sings the "Kai" song of life - the first advanced first-line premenopausal breast cancer CDK 4 6 inhibitor in China, Kai Lilong, was approved in China.
6.gabriel n.hortobagyi,m.d.et.al,overall survival with ribociclib plus letrozole in advanced breast cancer,n engl j med 2022;386:942-950
7.latest novartis kisqali®natalee analysis reinforces 25%reduction in risk of recurrence across broad population of patients with early breast cancer;supports regulatory submissions
8.novartis remibrutinib phase iii trials met their primary endpoints and showed rapid symptom control in chronic spontaneous urticaria
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