Lung cancer market battle is underway again

June 20, 2025  Source: drugdu 64

"/Recently, Ibtrozi (taletrectinib) developed by Nuvation Bio was approved by the US FDA for the treatment of adult patients with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC).

The drug is a highly selective, new-generation oral ROS1 tyrosine kinase inhibitor (TKI). In key trials, Ibtrozi demonstrated high response rates and lasting efficacy, and has the ability to penetrate the blood-brain barrier. Coupled with a clear and controllable safety profile, it is expected to become a new standard for targeted treatment of this type of lung cancer.

It is worth noting that the drug was approved for marketing in China in December 2024 for the first-line and second-line treatment of adult patients with ROS1-positive locally advanced or metastatic NSCLC, and Innovent Biologics is responsible for commercialization.

Potential BIC Therapies

Lung cancer is the leading cause of cancer death worldwide. Non-small cell lung cancer (NSCLC) is one of the most common types of lung cancer, accounting for 84% of diagnoses. The incidence of ROS1 fusions in all NSCLC patients is 1-2%, more common in lung adenocarcinoma; slightly higher in East Asian populations, at 2-3%.

Previously, the FDA has approved several tyrosine kinase inhibitors for the treatment of patients with ROS1-positive advanced NSCLC, including Pfizer's Xalkori (crizotinib), Roche's Rozlytrek (entrectinib), and BMS's Augtyro (ripretinib).

Although ROS1 fusion accounts for only 1-2% of non-small cell lung cancer (about 3,000 new cases are diagnosed each year in the United States), the competition is already fierce. Currently, Pfizer's first-generation ALK inhibitor Xalkori is gradually fading from the market due to limited efficacy, while Roche's Rozlytrek and BMS's Augtyro are the main players in the market.

Ibtrozi will compete with the star products of the three giants when it is launched. However, Ibtrozi still has a breakthrough advantage and has the potential of BIC.

Brain metastasis nemesis: The brain is the most common site of progression of ROS1 lung cancer. Ibtrozi can penetrate the blood-brain barrier. In key clinical trials, it was shown that the intracranial remission rate was 73% in first-line patients and 63% in previously treated patients (15/24 cases).

Good safety: Although BMS's Augtyro has strong efficacy, its central nervous system (CNS) side effects such as dizziness and cognitive impairment affect the medication experience and dosage optimization. Ibtrozi has higher selectivity for the ROS1 target, and there is no central nervous system safety warning in the label, with significant safety advantages. However, Ibtrozi needs to be alert to the cardiac risks of QT interval prolongation.

Impressive long-term survival data: Ibtrozi demonstrated high response rates and lasting clinical benefits in two single-arm studies, the Trust-I trial conducted in China and the Trust-II trial conducted globally.

In previously treated patients, the confirmed objective response rate (cORR) of taletrectinib in the TRUST-I and TRUST-II studies was 52% and 62%, respectively, and the median duration of response (mDOR) was 13.2 months (Trust-I).

Treatment-naive patients: The confirmed objective response rate (cORR) of taletrectinib in the TRUST-I and TRUST-II studies was 90% and 85%, respectively. Earlier pooled analysis showed that the median duration of response (DOR) of patients was 44.2 months, and the median progression-free survival (PFS) was 45.6 months (nearly 4 years). Compared with the DOR of 34 months and PFS of 35.7 months for Bristol-Myers Squibb's ripretinib, Ibtrozi showed better potential in terms of durability.

Small market gives birth to "$1 billion bomb"

The research and development history of taletrectinib is quite legendary.

Taletrectinib was originally developed by Daiichi Sankyo. In 2018, Biogen Pharmaceuticals reached a cooperation with Daiichi Sankyo to obtain the global development, production and commercialization rights of the drug. In June 2021, Innovent Biologics and Biogen Pharmaceuticals signed an exclusive license agreement to obtain the rights to jointly develop and commercialize taletrectinib in Greater China. In March 2024, Nuvation Bio acquired Biogen Pharmaceuticals and obtained the development rights of the therapy outside of Greater China.

In China, tacrolimus has been approved by NMPA for use as a first-line treatment for adult patients with ROS1-positive NSCLC who have progressed after ROS1-TKI treatment and for patients with ROS1-positive NSCLC who have not been treated with ROS1-TKI. Its trade name is Dabril.

The approval of Ibtrozi in the United States is another milestone on its road to commercialization. According to Nuvation Bio's estimates, there are about 3,000 newly diagnosed cases of ROS1-positive non-small cell lung cancer in the United States each year. Despite the small population covered, analysts still predict that Ibtrozi's peak sales will exceed US$1 billion, making it a "blockbuster".

On the one hand, the Ibtrozi drug itself has BIC advantages.

On the other hand, the updated guidelines have brought opportunities for Ibtrozi. In the past, patients diagnosed with lung cancer often received PD-1 immunotherapy + chemotherapy first. When the genetic test results (which take 2-3 weeks) showed ROS1 positive, many people were reluctant to change the drug, which severely limited the use of targeted drugs. In January this year, the authoritative NCCN guidelines in the United States were updated, explicitly prohibiting the use of immunotherapy for ROS1-positive patients, clearing the key obstacles for Ibtrozi to be launched.

In addition, David Hung, the actual controller of Nuvation Bio, is also a legendary figure. He founded Medivation and sold it to Pfizer for a sky-high price of US$14 billion in 2016, creating a classic merger and acquisition case in the history of biomedicine.

David Hung's second venture returns to the anti-cancer drug battlefield with Ibtrozi, directly challenging his former employer Pfizer, while also challenging the two giants Bristol-Myers Squibb and Roche. Can he break through the siege in the ROS1 market?

Conclusion

Among Chinese patients with non-small cell lung cancer, the frequency of ROS1 fusion positivity is relatively higher, at 2%-3%, but competition is also more intense. In addition to the aforementioned crizotinib, entrectinib, ripretinib, and taretinib, which have all been approved in China, there are also domestically developed products competing for the ROS1 lung cancer market.

Zhengda Tianqing's Anectinib was approved for marketing by NMPA in April 2024. It is the first domestically produced targeted drug approved for adult patients with ROS1-positive locally advanced or metastatic NSCLC and was included in the latest version of the National Medical Insurance Catalogue in November 2024. Its registration study data showed that Anectinib had an ORR of 81.08% in the overall population, mPFS was extended to 17.25 months, and the 24-month overall survival rate reached 82.18%.

In the trillion-dollar lung cancer market, although ROS1-positive patients are a niche group, the small market also has great potential. If excellent efficacy can be achieved and urgent clinical needs can be met, it can also become a "blockbuster."

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