Welcome to your weekly roundup of approaching clinical readouts. Data due before the end of the year could set Kalvista Therapeutics up for a good Christmas. A strong readout from a proof-of-concept trial of KVD001 in diabetic molecular oedema (DME) could tempt Merck & Co to opt in.
The big pharma company paid Kalvista $37m in 2017 for an option to KVD001, an intravitreal injection based on plasma kallikrein inhibition; its decision on whether to exercise the option depends on the data from the 124-patient trial. Merck also took options to earlier oral DME candidates, based on the same mechanism. Further payments of up to $715m are possible, though how these would be structured has not been disclosed.
Positive data would help validate this novel approach to treating the eye disease; sellside analysts covering Kalvista have largely held off assigning the project any value before the study reads out.
But Kalvista is the most advanced player in this space. The nearest rival asset, Oxurion/Bicycle Therapeutics’ THR-149, earlier this year yielded reassuring data showing a clean safety profile and signs of efficacy in a 12-patient phase I trial. THR-149 showed an average 7.5-letter increase in best corrected visual acuity 14 days after a single injection.
Expectations for KDV-001’s visual acuity gains are more modest, given the larger trial size, with observers looking for three to five-letter improvement as a base case. The project’s safety profile will also have huge bearing on sentiment given the excellent safety of other macular oedema products on the market.
VEGF inhibitors like Lucentis and Eylea are commonly used in DME, and Kalvista is focusing on the estimated 40% of DME patients who do not respond adequately to these. Leerink has estimated that peak sales of a product that could target this niche could reach $2bn worldwide, though Kalvista and others must first prove that plasma kallikrein inhibition has a place here.
|Kallikrein inhibitors for diabetic macular oedema|
|KVD001||Kalvista (Merck & Co option)||NCT03466099|
|THR-149||Oxurion (from Bicycle Therapeutics)||NCT03511898|
|RZ402||Rezolute (from Activesite)||n/a|
Sanofi fights on
Meanwhile, Genmab’s Darzalex won the race to become the first CD38-targeting multiple myeloma drug to market, but Sanofi is not giving up the fight. The French group filed its me-too antibody, isatuximab, earlier this year, and will shortly see the results of another pivotal study, Ikema, seeking to broaden the addressable population.
Ikema is due to yield data in the first quarter of next year. It pits isatuximab, in combination with Kyprolis and dexamethasone, against Kyprolis and dexamethasone alone in 302 subjects treated with one to three prior lines of therapy; progression-fee survival is the primary endpoint.
The setting is broadly analogous to Darzalex’s approved use on the back of the Castor study, in which the Genmab drug was given second line in combination with Velcade and dexamethasone. Here the Genmab combo posted a 16.7-month median PFS, versus 7.1 months for Velcade and dexamethasone alone (HR=0.32, p<0.0001).
Isatuximab’s first use is expected to be third line, in combination with Pomalyst plus dexamethasone, on the back of the Icaria trial that yielded positive data earlier this year. Jefferies analysts expect approval by its second-quarter 2020 US FDA action date, but do not think that the Sanofi asset marks a great improvement over Darzalex.
Indeed, EvaluatePharma sellside consensus sees isatuximab posting 2024 revenue of just $449m, versus Darzalex’s $5.4bn. Additional Sanofi trials will seek to expand the settings further, but investors will note early threats from Takeda/Molecular Templates' TAK-169, not to mention Genmab’s own Darzalex follow-on, HexaBody-CD38, partnered with Johnson & Johnson.
|Duelling anti-CD38 MAbs in multiple myeloma|
|Approved Darzalex use||Corresponding isatuximab setting||Sanofi trial||Isatuximab strategy|
|3L, Pomalyst + dex combo||3L, Pomalyst + dex combo||Icaria||Filed, 20 Apr 2020 PDUFA|
|2-4L, Velcade + dex combo||2-4L, Kyprolis + dex combo||Ikema||Data & filing 2020|
|1L transplant-ineligible, Velcade combo||1L transplant-ineligible, Velcade + Revlimid + dex combo||Imroz||Data & filing 2021|
|1L, Revlimid + dex combo||1L, Revlimid + Velcade + dex combo||GMMG||Completion May 2025|
|Source: clinicaltrials.gov & company statements.|