Nuvalent Receives U.S. FDA Breakthrough Therapy Designation for NVL-655
Nuvalent announced that the FDA has granted breakthrough therapy designation (BTD) for NVL-655, a novel ALK-selective tyrosine kinase inhibitor (TKI) designed to treat locally advanced or metastatic ALK-positive non-small cell lung cancer (NSCLC) in patients previously treated with two or more ALK TKIs. ALK rearrangements occur in up to 5% of metastatic NSCLCs, with 40% of these patients presenting brain metastases at diagnosis, and 50% developing resistance mutations after treatment. NVL-655 aims to address these challenges with brain-penetrant properties and minimal off-target CNS adverse events. The BTD is based on Phase 1 trial results, with Phase 2 enrollment ongoing. Nuvalent plans an update from the ALKOVE-1 trial in the second half of 2024.
- FDA granted breakthrough therapy designation (BTD) to NVL-655.
- NVL-655 addresses treatment resistance and brain metastases in ALK-positive NSCLC.
- The BTD is based on positive preliminary safety and activity data from Phase 1 trials.
- Nuvalent plans to provide an update on NVL-655 in the second half of 2024.
- BTD accelerates development and review processes, providing intensive FDA guidance and eligibility for rolling review.
- No clear standard of care exists for patients after treatment with two or more ALK TKIs.
- 50% of ALK-positive NSCLC patients develop resistance mutations after initial treatments.
- The final efficacy and safety of NVL-655 are still pending further clinical trials.
- The success of NVL-655 relies on continued positive results, which are not guaranteed.
The FDA's breakthrough therapy designation (BTD) for NVL-655 indicates a significant step forward in the treatment of ALK-positive non-small cell lung cancer (NSCLC). The drug's ability to penetrate the brain and selectively target ALK while avoiding off-target CNS adverse events positions it as a potential game-changer for patients who have developed resistance to other treatments. This designation could expedite the drug's development and review, potentially bringing a new treatment option to a patient population with high unmet needs.
The BTD is particularly noteworthy as it reflects preliminary clinical evidence suggesting significant improvements over existing therapies. This could lead to accelerated approval timelines and earlier market entry, giving Nuvalent a competitive edge in the oncology market. For patients, this means faster access to a potentially more effective treatment option, which is important given the high rates of brain metastases and resistance mutations in this cancer subset.
The FDA BTD for NVL-655 is poised to have a substantial impact on Nuvalent's financial outlook. This designation often leads to increased investor confidence and can drive stock prices higher due to the potential for expedited market entry and reduced costs associated with the drug's development and review process. Additionally, the company's ability to showcase promising data from the Phase 1 ALKOVE-1 trial further solidifies the drug's potential efficacy and market viability.
From a financial perspective, the breakthrough designation could attract partnerships or investments, providing Nuvalent with the necessary capital to accelerate further clinical trials and ultimately commercialize NVL-655. The oncology drug market is highly lucrative and capturing a share of the ALK-positive NSCLC segment could significantly boost Nuvalent's revenue streams in the long term.
The FDA's BTD for NVL-655 is a promising development in the ongoing battle against ALK-positive NSCLC. As an oncologist, the ability to offer patients a novel treatment that addresses the dual challenges of brain metastases and resistance mutations is particularly encouraging. Current therapies often fall short in these areas, leaving a critical gap in effective treatment options for patients who have exhausted other ALK inhibitors.
The preliminary data indicating NVL-655's safety and activity in this heavily pretreated patient population is hopeful. However, it is essential to remain cautiously optimistic until more comprehensive data from the Phase 2 portion of the trial is available. If these results continue to be favorable, NVL-655 could significantly improve patient outcomes and become a new cornerstone in the treatment of ALK-positive NSCLC.
ALK rearrangements occur in up to approximately
NVL-655 is a novel brain-penetrant ALK-selective TKI created with the aim to simultaneously overcome the clinical challenges of emergent treatment resistance, brain metastases, and off-target central nervous system (CNS) adverse events associated with inhibition of the structurally-related tropomyosin receptor kinase (TRK) family.
"Today's announcement of FDA breakthrough therapy designation for NVL-655 marks another important milestone for our ALK program and the second breakthrough designation granted to our pipeline of novel kinase inhibitors this year," said Darlene Noci, A.L.M., Chief Development Officer at Nuvalent. "Our team is committed to expeditiously advancing NVL-655 in recognition of the continued need for innovation for patients with ALK-positive NSCLC who have exhausted available therapies. We expect to provide an update from the ALKOVE-1 trial of NVL-655 at a medical meeting in the second half of this year."
BTD is designed to expedite the development and review of therapies intended to treat a serious or life-threatening condition and whose preliminary clinical evidence indicates that the drug may demonstrate substantial improvement on one or more clinically significant endpoints over existing available therapies. Under the designation, the FDA provides intensive guidance, organizational commitment involving senior managers, and eligibility for rolling review and other actions to expedite review.
The BTD for NVL-655 is based on the preliminary safety and activity of NVL-655 in heavily pretreated patients with advanced ALK-positive NSCLC in the Phase 1 portion of the Phase 1/2 ALKOVE-1 clinical trial. Enrollment in the Phase 2 portion of the trial is ongoing, and the company expects to share updated data from the trial at a medical meeting in the second half of 2024.
About NVL-655
NVL-655 is a novel brain-penetrant ALK-selective inhibitor created with the aim to overcome limitations observed with currently available ALK inhibitors. NVL-655 is designed to remain active in tumors that have developed resistance to first-, second-, and third-generation ALK inhibitors, including tumors with single or compound treatment-emergent ALK mutations such as G1202R. In addition, NVL-655 is designed for central nervous system (CNS) penetrance to improve treatment options for patients with brain metastases, and to avoid inhibition of the structurally related tropomyosin receptor kinase (TRK) family. Together, these characteristics have the potential to avoid TRK-related CNS adverse events seen with dual TRK/ALK inhibitors and to drive deep, durable responses for patients across all lines of therapy. NVL-655 has received orphan drug designation for ALK-positive non-small cell lung cancer (NSCLC) and is currently being investigated in the ALKOVE-1 clinical trial (NCT05384626), a first-in-human Phase 1/2 clinical trial for patients with advanced ALK-positive NSCLC and other solid tumors.
About Nuvalent
Nuvalent, Inc. (Nasdaq: NUVL) is a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for patients with cancer, designed to overcome the limitations of existing therapies for clinically proven kinase targets. Leveraging deep expertise in chemistry and structure-based drug design, we develop innovative small molecules that have the potential to overcome resistance, minimize adverse events, address brain metastases, and drive more durable responses. Nuvalent is advancing a robust pipeline with investigational candidates for ROS1-positive, ALK-positive, and HER2-altered non-small cell lung cancer, and multiple discovery-stage research programs.
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, implied and express statements regarding Nuvalent's strategy, business plans, and focus; the expected timing of data announcements; the clinical development program for NVL-655; the potential clinical effect of NVL-655; the design and enrollment of the ALKOVE-1 trial, including its intended pivotal registration-directed design; the potential of Nuvalent's pipeline programs, including NVL-655; Nuvalent's research and development programs for the treatment of cancer; and risks and uncertainties associated with drug development. The words "may," "might," "could," "would," "should," "expect," "plan," "anticipate," "aim," "goal," "intend," "believe," "expect," "estimate," "seek," "predict," "future," "project," "potential," "continue," "target" or the negative of these terms and similar words or expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Drug development and commercialization involve a high degree of risk, and only a small number of research and development programs result in commercialization of a product. You should not place undue reliance on these statements or the scientific data presented.
Any forward-looking statements in this press release are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties, and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation: risks that Nuvalent may not fully enroll the ALKOVE-1 trial or that enrollment will take longer than expected; unexpected concerns that may arise from additional data, analysis, or results obtained during preclinical studies or clinical trials; the risk that results of earlier clinical trials may not be predictive of the results of later-stage clinical trials; the risk that data from our clinical trials may not be sufficient to support registration and that Nuvalent may be required to conduct one or more additional studies or trials prior to seeking registration of our product candidates; the occurrence of adverse safety events; risks that the FDA may not approve our potential products on the timelines we expect, or at all; risks of unexpected costs, delays, or other unexpected hurdles; the direct or indirect impact of public health emergencies or global geopolitical circumstances on the timing and anticipated timing and results of Nuvalent's clinical trials, strategy, and future operations, including the ALKOVE-1 trial; the timing and outcome of Nuvalent's planned interactions with regulatory authorities; risks related to obtaining, maintaining, and protecting Nuvalent's intellectual property. These and other risks and uncertainties are described in greater detail in the section entitled "Risk Factors" in Nuvalent's Quarterly Report on Form 10-Q for the quarterly period ended March 31, 2024, as well as any prior and subsequent filings with the Securities and Exchange Commission. In addition, any forward-looking statements represent Nuvalent's views only as of today and should not be relied upon as representing its views as of any subsequent date. Nuvalent explicitly disclaims any obligation to update any forward-looking statements.
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