Crucial clinical events for the smaller players
Data are due in the fourth quarter for Aldeyra, Aeglea and Radius, among other small developers.
Aeglea’s lead project, pegzilarginase, will yield pivotal results in an ultra-rare disease, and Radius hopes to validate its Serd elacestrant ahead of the competition. Meanwhile, Aldeyra’s reproxalap, which has already prevailed in allergic conjunctivitis, will see data in the bigger, and more crowded, indication of dry eye disease.
Aldeyra’s two phase 3 dry eye studies, Tranquility and Tranquility-2, include 300 patients each and are based on a chamber challenge model with dry air. In the two-day regimen patients receive either topical reproxalap or vehicle four times on day one, then on day two they are dosed just before entering the chamber and again 45 minutes afterwards.
The primary measure is ocular redness, assessed over 90 minutes in the dry eye chamber. Earlier this year the redness measure was met in an allergic conjunctivitis study (Aldeyra eyes the future, April 27, 2021). Reproxalap inhibits reactive aldehyde species, which are said to be elevated in numerous inflammatory diseases.
Aldeyra is not the only group trying to take on current dry eye drugs such as Abbvie’s Restasis and Novartis’s Xiidra. Bausch already had one win with its lipid modulator Nov03, and is expected to report data from the second study in the fourth quarter, while an approval decision on Oyster Point’s nasal formulation of Chantix, OC-01, is due in October.
Rare disease target
Pivotal phase 3 data are expected from Aeglea’s lead project, pegzilarginase, a recombinant arginase 1 enzyme designed to lower levels of arginine in patients with arginase 1 deficiency (Arg1-D).
Current treatments for the rare progressive disease include severe dietary protein restriction, amino acid supplementation and ammonia scavengers.
Aeglea’s Peace study, in 32 Arg1-D patients aged two years and older, involves weekly intravenous infusions of pegzilarginase for 24 weeks versus placebo. The primary endpoint is change from baseline in plasma arginine concentration, with mobility assessments as a secondary measure.
56-week data from a small earlier study were encouraging, with all 13 patients achieving plasma arginine levels under 200µM, the target set in disease management guidelines. The median plasma arginine level was 99µM, compared with 389µM at baseline.
Regarding mobility assessments, the overall response rate was 85% and meeting these secondary endpoints in the pivotal study will be important.
Elacestrant, Radius/Menarini’s selective oestrogen degrader, is due to yield data soon in advanced breast cancer, setting up a showdown with Sanofi’s competing project amcenestrant. Readout from Sanofi's Ameera-3 study had been expected earlier in the year, but has been delayed.
Radius’s Emerald trial, in second or third-line ER-positive/Her2-negative disease, tests elacestrant monotherapy versus standard of care, which includes Faslodex or an aromatase inhibitor. The co-primary endpoints are PFS in patients with oestrogen receptor 1 (ESR1) mutations and all comers. ESR1 mutation is a key resistance mechanism to endocrine therapy.
Roche, Astrazeneca and Lilly are all also vying for Serd validation. Ongoing studies from the big pharma companies in first-line disease will start reporting in 2024 (The search for a better Faslodex continues, July 26, 2021).
The table below contains a fuller list of upcoming catalysts with consensus forecasts from Evaluate Pharma.
|Q4 clinical catalysts (excludes Covid-19 data)|
|Product||Company||Therapy area||Q4 clinical catalyst||2026e indication sales ($m)||Note/Vantage coverage|
|Radius||Male osteoporosis||Ph3 Atom||329*||Results to be included in sNDA to add males to label; Stifel notes this will add ~10% to addressable population|
|Reproxalap ophthalmic solution||Aldeyra||Dry eye||Ph3 Tranquility, Tranquility-2 (confirmatory)||312||See text|
|Pegzilarginase (AEB1102)||Aeglea||Arginase 1 deficiency||Topline pivotal Ph3 Peace||252||See text|
|FLT190||Freeline||Fabry disease||Ph1/2 Marvel-1 by YE||251||Gene therapy|
|MEI Pharma||3L+ r/r follicular lymphoma||Ph2 Tidal||247||PI3k delta inhibitor; complete data from FL arm are to be submitted to the FDA to support accelerated approval|
|Mereo||Solid tumours||Phase 1b/2 Activate basket study + Opdivo||160||Anti-Tigit MAb, ~20 pts worth of response and biomarker data; interest in Tigit remains high (Glaxo pays handsomely to join the Tigit chase)|
|XEN1101||Xenon||Adult focal seizures||Ph2b X-Tole||148||Potassium channel modulator, adjunctive treatment|
|COM701 + Opdivo + BMS-986207||Compugen/Bristol Myers Squibb||Advanced solid tumours||Ph1/2 dose escalation||145||Bristol's Tigit, Compugen's anti-PVRIG MAb; Glaxo also has an anti-PVRIG SRF813 via Surface (No Surface buyout, but Glaxo picks another cancer target)|
|Elacestrant||Menarini/Radius||2nd/3rd-line ER+/Her2- breast cancer||Ph3 Emerald, versus standard of care||69||See text|
|COM902||Compugen||Advanced cancer||Ph1 monotherapy dose escalation||2||Anti-Tigit (Fc-silent)|
|Cosibelimab||Checkpoint/Fortress||Metastatic cutaneous squamous cell carcinoma||Cohort data in Ph1 registration enabling study||-||Anti-PD-L1 (No fast way to eighth place for Incyte)|
|PBGM01||Passage Bio||Early and late infantile GM1 gangliosidosis||Ph1/2 Imagine-1 safety and 30-day biomarker||-||Gene therapy, should also see data from Sio's AXO-AAV-GM1 in Q4 (A three way battle beckons in GM1 gangliosidosis)|
|Annovis Bio||Alzheimer's and Parkinson's diseases||Ph2a full data early fall||-||AAIC – speculative Alzheimer’s groups fail to catch the Aduhelm wave|
clonal neoantigen T cell (cNeT) therapy
|Achilles||NSCLC, melanoma||Ph1/2 Chiron and Thetis update||-||TIL therapy, data expected from 10 patients across the two studies who have received monotherapy|
|Checkmate Pharmaceuticals||Head and neck squamous cell carcinoma||Ph2 before YE||-||TLR9 agonist; in combination with Keytruda|
|*Already approved. Sources: Evaluate Pharma, company releases, analyst notes & clinicaltrials.gov.|