Novartis has entered into a significant licensing agreement with South Korean pharmaceutical company Chong Kun Dang (CKD) for CKD-510, an investigational HDAC6 inhibitor with potential applications in Charcot-Marie-Tooth (CMT) disease. The deal, announced on November 6, could be worth up to $1.3 billion, marking a substantial investment in rare disease therapeutics.
Under the terms of the agreement, Novartis will make an upfront payment of $80 million to CKD, with additional development and regulatory milestone payments potentially reaching $1.23 billion. CKD will also remain eligible for sales-based royalties and ongoing technology fees based on net sales. In exchange, Novartis gains exclusive global rights to develop and commercialize CKD-510, except in Korea, where CKD retains the rights.
Promising Therapeutic for Rare Neurological Disease
CKD-510 functions as an inhibitor of histone deacetylase 6 (HDAC6) and has already received orphan drug designation from the U.S. Food and Drug Administration (FDA) in March 2020 for the treatment of CMT disease. This rare, hereditary neurological condition affects the peripheral nerves in the limbs, causing progressive muscle weakness, pain, and numbness.
The drug candidate successfully completed a Phase I first-in-human study in 2021, involving 87 healthy volunteers, which confirmed its safety and tolerability profile. Preclinical studies have demonstrated efficacy in treating not only CMT but also cardiovascular conditions such as atrial fibrillation, where it showed improvements in acetylated alpha-tubulin and action potential duration.
A CKD official told Korea Biomedical Review that the specific indication for CKD-510 "has not been specified yet," adding that "efficacy for various diseases has been confirmed through many clinical and non-clinical studies, and indications will be confirmed through partners in the development process."
Strategic Expansion in CMT Therapeutics
This acquisition represents Novartis' second recent investment in CMT treatments, following its July procurement of DTX-1252, another potential therapeutic for CMT1A. The substantial financial commitment signals Novartis' strategic interest in expanding its rare disease portfolio, particularly in neurological conditions with significant unmet medical needs.
HDAC6 has been a focal point of CMT research for years, with initiatives supported by the Charcot-Marie-Tooth Association's Strategy to Accelerate Research (CMTA-STAR). The enzyme regulates mitochondrial function and intracellular transport along microtubules, processes that are critical for peripheral nerve health. Due to their length, peripheral nerves are particularly sensitive to disruptions in this transport, which can lead to the characteristic symptoms of CMT.
Dr. Amy Gray, CEO of the Charcot-Marie-Tooth Association, commented: "The scale of this transaction reflects the progress made in positioning CMT as an attractive proposition for pharmaceutical companies, which has been one of the strategic aims of our STAR research initiative."
Novartis' Portfolio Restructuring
This new partnership comes amid Novartis' broader efforts to streamline its business and refocus its portfolio. In September 2023, the Swiss pharmaceutical giant completed the spin-off of its generics and biosimilars division, Sandoz, more than a year after announcing plans for the spinout.
During the same period, Novartis terminated several other partnerships and development programs. The company discontinued its 2021 collaboration with BeiGene for the development of the anti-PD-1 antibody tislelizumab for various oncology indications. It also halted development of the mid-stage gene therapy GT005 for geographic atrophy secondary to dry age-related macular degeneration, which it had acquired through its $800 million purchase of Gyroscope Therapeutics in December 2021.
However, not all of Novartis' recent partnerships have ended in discontinued programs. Last week, the company reported positive results from the Phase III ALIGN study of atrasentan, an endothelin A receptor antagonist for IgA nephropathy, which Novartis acquired through its $3.2 billion purchase of Chinook Therapeutics in June 2023.
Implications for CMT Treatment Landscape
For the estimated 2.8 million people worldwide affected by CMT, the Novartis-CKD partnership represents a significant development in the therapeutic landscape. Currently, there are no FDA-approved treatments specifically for CMT, with management focused primarily on symptom control and supportive care.
The orphan drug designation granted to CKD-510 provides Novartis with incentives such as tax credits for qualified clinical trials and exemption from user fees in the United States, potentially accelerating the development timeline.
Animal studies in various peripheral neuropathy models have identified HDAC6 inhibition as a promising therapeutic approach to restore nerve function and alleviate symptoms. If successful in clinical development, CKD-510 could become one of the first disease-modifying treatments for this debilitating neurological condition.
The Charcot-Marie-Tooth Association has indicated it is closely monitoring these developments and will share additional information with the CMT community as it becomes available.
