KalVista's diabetic macular edema data falls short — will Merck walk away?
Two doses of the intravitreal injection, KVD001, were tested against a placebo in a 129-patient trial. Patients who continued to experience significant inflammation and diminished visual acuity, despite anti-VEGF therapy, were recruited to the trial. Typically patients with DME — the most frequent cause of vision loss related to diabetes — are treated with anti-VEGF therapies such as Regeneron’s flagship Eylea or Roche’s Avastin and Lucentis.
KVD001 is engineered to inhibit an enzyme called plasma kallikrein and was developed on the basis of research that indicated enhanced levels of the protein are present in the vitreous fluid in the eyes of people with DME. Preclinical data suggest plasma kallikrein inhibition is key to a decline in retinal thickening and better processing of visual signals, according to KalVista.
However, neither dose of KVD001 met the main goal of the Phase II study, which was to induce a statistically significant change in best-corrected visual acuity (BCVA) at 16 weeks versus placebo (6 μg = +2.6 letters or 3 μg = +1.5 letters; p=0.465). No significant differences from placebo emerged on any of the secondary endpoints including central subfield thickness or the diabetic retinopathy severity scale, the company said, adding that the drug was generally safe and well-tolerated.
The company’s stock tumbled $KALV more than 17% to $11.88 in premarket trading.
Still, KalVista highlighted some silver linings from subgroup analyses that chief Andrew Crockett said could justify further study of the drug in the DME population.
Patients given the higher dose of KVD001 saw a slower reduction in vision loss at 32.5% versus placebo at 54.5%, although the difference was not deemed statistically significant (p=0.042). After excluding patients with the most severe levels of vision loss, the remaining 70% of the total patient population showed a difference in BCVA compared to placebo of 4.9 letters at the 6 μg dose, although again the difference was not statistically significant (p=0.056).
“From a look at the data and various secondary/subgroup analyses it does appear that there were some trends towards benefit in the study, but we doubt it will gain credit from investors in the absence of another corroborating trial,” Stifel’s Paul Matteis wrote in a note, indicating that the failure is not a huge surprise.
In 2017, Merck paid $8.50 a share for a 10% stake in KalVista and a further $37 million upfront for an option to buy KVD001.
“We think investors buying the stock today should largely assume that this program won’t move forward. If Merck passes on the asset it’s possible KALV could look for another partner, but again, figuring out the next steps here, if there are any, may take time,” Matteis said.
Endpoints News has contacted Merck for comment.
KalVista has another plasma kallikrein inhibitor in its arsenal, the oral therapy KVD900, under development for hereditary angioedema (HAE). Data from a Phase II trial are expected next year.
“(W)e see no readthrough onto KVD900: in HAE plasma kallikrein is a validated target, and in DME it is an interesting target that, unlike in HAE, has never before been the foundation for approved/effective drugs,” Matteis noted. “In turn, we continue to gain optimism in the prospects for KVD900, based on the success of other medications in the space, and our work…based on the triangulation of PK/PD data which we think support ‘900 as an oral rescue med with potential “injection-like” efficacy.”