- Iowa-based NewLink Genetics saw its shares slide nearly 10% Tuesday after reporting interim results from a Phase 2 trial combining its experimental immunotherapy with Merck's Keytruda (pembrolizumab).
- Pairing NewLink's indoximod with Keytruda led to a 52% response rate among patients with advanced melanoma, a result which NewLink says underscores the potential to improve the efficacy of checkpoint inhibitors by adding other inhibitory therapies to treatment.
- The data, presented at the annual meeting of the American Association of Cancer Research, appeared to fall short of market expectations, leading to the sell-off. While NewLink's data did measure up to response rates seen in a study of Keytruda monotherapy among advanced melanoma patients, another similar drug from Inctye Corp. is further along in testing.
NewLink seems to have suffered the ill effects of comparison to Incyte's rapidly advancing epacadostat. Both drugs target the so-called IDO pathway, aiming to block inhibitory signaling that allows cancer cells to avoid an immune response.
Indoximod, however, works slightly different than epacadostat, acting directly on immune cells to reverse immunosuppression. Incyte's drug, by comparison, inhibits the IDO enzyme itself.
IDO inhibitors are being closely watched as a potential second generation of immunotherapies that could complement existing checkpoint inhibitors.
"If you can make an immune doublet that can make the punch of a CTLA4 [inhibitor] without the toxicity it brings to a combination, that would much more tolerable for patients and much more easily adopted into the community," said NewLink CEO Charles Link, reached after publication of the results.
Among the 60 patients in NewLink's Phase 2 study who were evaluable at the interim data cut-off, treatment with indoximod and Keytruda led to an objective response rate of 52%, with 6% experiencing a complete response.
Nine patients, however, had ocular melanoma, which tends to be more aggressive and less responsive to therapy. Excluding those patients results in a 59% response rate, a data point which NewLink highlighted in its press release on the news.
"It is noteworthy that this trial did not exclude ocular melanoma, which has been shown to be more aggressive and less responsive to available systemic treatment," said Yousef Zakharia, a lead investigator for the trial, in a written statement. "Most comparable trials do not allow patients with ocular melanoma."
Nick Vahanian, NewLink's chief medical officer, said in an emailed reply to questions that separate consideration of the two populations could be appropriate given data that suggests ocular melanoma doesn't respond to PD-1 inhibition. NewLink's Phase 2 study doesn't separate out the two groups, however.
In a 2015 Phase 3 trial comparing Keytruda to Bristol-Myers Squibb's Yervoy (ipilimumab) in advanced melanoma, treatment with Keytruda led to a 33% response rate and between a 5% and 6% complete response (depending on the dose). While comparing studies is always fraught with statistical risks, adding indoximod to Keytruda seemed to improve on those results somewhat.
The primary endpoints in that trial, however, were progression-free survival (PFS) and overall survival — data which has not been presented yet by NewLink for indoximod as median PFS has not been reached.
NewLink's CEO said the biotech is eager to push indoximod into Phase 3 testing later this year to follow up on the efficacy signal seen to date. "With this data and with Incyte out there already holding their Phase 3 trial, we want stay neck and neck with them," Link explained.
Incyte has already pushed into Phase 3 testing of epacadostat paired with Keytruda, and early Phase 1 results suggested higher efficacy among advanced melanoma patients than indoximod plus Keytruda.
But that data is from a smaller number of patients than the indoximod results released Tuesday, making comparisons on the basis of public data more difficult.
Incyte made waves at this AACR conference, inking deals with both Bristol-Myers and Merck to advance epacadostat plus Opdivo (nivolumab) or Keytruda, respectively, into Phase 3 testing — staking out a leading position in the IDO space.
NewLink shares regained some their value as the day progressed, climbing back from being down over 25% to closing down about 10%.
Editor's note: This post has been updated to include comments from NewLink Genetics CEO Charles Link, who was interviewed by BioPharma Dive following publication.