IO Biotech’s lead cancer vaccine asset, Cylembio (imsapepimut and etimupepimut, adjuvant), has narrowly missed its primary endpoint of improved PFS in a Phase III clinical trial in advanced melanoma.
Despite this topline outcome, IO Biotech still plans to submit a biologics license application (BLA) to the US Food and Drug Administration (FDA) for Cylembio in an advanced melanoma setting by the end of 2025, said the company’s CEO, Mai-Britt Zocca, during an investor call on 11 August.
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Investors were seemingly not convinced by IO Biotech’s plans for Cylembio, with the company’s stock dropping by 27% after the call, from $1.88 at market open on 11 August to $1.37 at 12 pm Eastern Time (ET) on the same day.
If approved, Cylembio would be the first cancer vaccine to get the FDA green light in an advanced melanoma patient population.
The Phase III IOB-013/KN-D18 trial (NCT05155254) compared the efficacy and safety of Cylembio in combination with Merck’s Keytruda (pembrolizumab) versus Keytruda alone. The trial found that the combination therapy offered a median PFS (mPFS) benefit of 19.4 months versus 11 months with Keytruda alone.
While the combination reduced the risk of disease progression or death by 23%, the result was not statistically significant, with a p-value of 0.056 compared to the desired p≤0.045.
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By GlobalDataThough not mature, a trend in overall survival (OS) improvement has also been observed, with the OS data reading out in the next six months.
Notably, a post-hoc analysis conducted in patients without prior anti-PD-1 treatment showed that Cylembio plus Keytruda offered significant improvements in mPFS values, increasing from 19.4 months to 24.8 months.
During the call, investors voiced concerns around the number of patients recruited in the US for this study, which stood at 17 of the 407 enrolled, with questions asked about whether the FDA could ask for a second trial for better US patient representation.
IO’s CMO, Qasim Ahmad, dismissed these claims, stating that the biotech “does not see any risk adherent to these parts of our filings,” due to its ongoing conversations with the regulator on the execution of this trial.
Ahmad also stated that 90% of the trial’s participants were Caucasian, Western European patients, which IO believes will satisfy the agency with their requirements of trials that represent the US population.
Cancer vaccine race is on
Though there is a wide range of drugs approved for the treatment of melanoma, patients with unresectable, advanced iterations of the disease often experience poor outcomes, with 50% of patients relapsing within the first year of treatment with standard of care (SoC) Keytruda.
This means that many pharma companies are aiming to fulfil the unmet need of refractory patients, with GlobalData’s Intelligence Centre (IC) revealing there are 2,308 ongoing clinical trials within the melanoma space currently.
Despite the competitive nature of the melanoma market, analysts at GlobalData, parent company of Clinical Trials Arena, forecast that Cylembio could make $495m by 2031 if approved.
According to Zocca, the company will support the timely rollout of Cylembio if approved through its commercial-scale manufacturing and global supply chain, which is “already in place”.
IO may face stiff competition with Moderna and MSD’s vaccine candidate, mRNA-4157, which is hot on Cylembio’s tail, currently being investigated in Phase III trials for advanced melanoma.
If approved, mRNA-4157 would be a significant competitor of Cylembio, as the jab is personalised to the user’s tumour microenvironment, while the latter can only kill tumour and immune-suppressive cells expressing indoleamine 2,3-dioxygenase 1 (IDO1) positive and/or programmed death-ligand 1 (PD-L1).
