Fourth-quarter data for the little guys
Relmada, Albireo and Mirum prepare for important clinical results, as Intercept is set back again.
Evaluate Vantage has already delved into the key upcoming fourth-quarter data for big pharma and large biotech groups. Now it is the turn of companies with a market cap under $1bn.
Relmada will reveal the first late-stage results with its depression project REL-1017, although concerns over abuse potential could hinder its commercial prospects. Elsewhere, Albireo and Mirum are jostling for space in the rare paediatric biliary disorder market.
One catalyst came today as Intercept revealed that Ocaliva failed in the Reverse study in advanced Nash patients. The company still plans to file in patients with stage 2 or 3 liver fibrosis due to Nash, but recent reanalysis of data from the Regenerate trial provided little solace. Intercept, which got a complete response letter two years ago, will have to watch out for Madrigal stealing its Nash crown as pivotal data with resmetirom are expected soon.
Onto upcoming fourth quarter readouts, Relmada’s major depressive disorder asset REL-1017 is set to yield data from three phase 3 studies, two as an adjunctive treatment and one as monotherapy.
There is a lack of previous monotherapy data, though REL-1017 did show a strong phase 2 result in an adjunctive setting. Here there was an 8.7 and 7.2-point placebo-adjusted MADRS depression score reduction from baseline at day 7, respectively in the 25mg and 50mg cohorts. 25mg is the phase 3 dose, and 28-day change in MADRS is the primary measure for all three upcoming studies.
Mizuho analysts assume a 3.8-point placebo-adjusted reduction on MADRS for the upcoming adjunctive trials, above the two-point reduction for which the studies are powered.
REL-1017 is an isomer of methadone, so safety will be key. Relmada’s therapy has already shown significantly different abuse potential than Ketamine or Oxycodone, but there are still concerns over how the FDA and DEA may restrict use.
Safety issues aside, Relmada is also playing in a crowded space; Axsome’s Auvelity recently gained FDA approval, and Biogen/Sage’s zuranolone is undergoing a rolling submission. Stifel cites a key opinion leader predicting fifth or sixth-line use, at best, for REL-1017.
Mirum and Albireo are vying for a space in Alagille syndrome and progressive familial intrahepatic cholestasis (PFIC), running higher-dose studies of their drugs targeting each other’s approved indications.
Albireo’s Bylvay is approved in PFIC and Mirum’s Livmarli in Alagille syndrome, which is a slightly bigger use. Both therapies are bile acid transporter inhibitors used to reduce pruritus or itching, a troublesome symptom. It has not been determined whether either therapy can delay disease progression or the need for a liver transplant.
Now Albireo wants to add Alagille to its label, with a phase 3 study testing a daily 120ug/kg dose. Bylvay's approved dose in PFIC is 40ug/kg per day with an increase to 120ug/kg daily if there are no improvements in pruritus after 3 months. The primary endpoint of the Assert study in Alagille is change in 24-week scratching score versus placebo, with a change in bile acid levels and safety as secondaries.
Meanwhile Mirum hopes to score in PFIC with 570ug/kg twice daily; Livmarli's approved dose in Alagille is once-daily 380ug/kg. The primary measure of the phase 3 March-PFIC study is mean change in average morning itching score up to 26 weeks. Primary cohort patients include those with PFIC type 2, with a supplemental cohort including PFIC 1, 3 and 4. Albireo’s Bylvay is approved in types 1 and 2 patients.
A dose-response analysis by Evercore suggests that Mirum could win in both PFIC and Alagille, with the potential for Livmarli's higher dose yielding differentiated results in PFIC, a scenario that seems less likely for Albireo’s Bylvay in Alagille.
The table below contains a fuller list of upcoming catalysts with consensus forecasts from Evaluate Pharma.
|Small companies' 4th-quarter clinical catalysts|
|Project||Company||Therapy area||Q4 clinical catalyst||2028e indication sales ($m)||Note/ Vantage coverage|
|Bylvay||Albireo||Pruritus in Alagille syndrome||Ph3 Assert||649*||See text|
|Ensifentrine||Verona||Maintenance treatment of COPD||Ph3 Enhance-1||601||First phase 3, Enhance-2, met primary endpoint|
|REL-1017||Relmada||Major depressive disorder||Ph3 Reliance III monotherapy, Reliance I and II adjunctive||570||See text|
|Obe-cel||Autolus||Adult ALL||Topline pivotal Felix||423||Anti-CD19 Car-T; passed futility analysis, full data expected at conference H1 2023 and expected to form basis of BLA|
|RP1||Replimune||Anti-PD-1 failed melanoma||Ph2 Ignyte, 75 patients, 6mth follow-up||297||Registration-directed single-arm study|
|STS101||Satsuma||Acute treatment of migraine||Ph3 Summit||261||Previous failure in ph3 Emerge study (Satsuma’s second chance nears readout)|
|IMA203||Immatics||Solid tumours||Ph1b expansion cohort B (+ Opdivo) and cohort C (next gen IMA203CD8) YE||260||Prame-directed engineered T-cell receptor asset (SITC 2021 – Immatics’ T-cell receptor success was no fluke)|
|Cosela (trilaciclib)||G1 Therapeutics||Neoadjuvant breast cancer, bladder cancer||Ph2 TNBC study, Ph2 Preserve 3 + chemo + Bavencio (bladder) initial data||215||CDK4/6 inhibitor; Lilly and Pfizer own this space in breast cancer|
|Mirum||Pruritus in progressive familial intrahepatic cholestasis||Ph 3 March-PFIC||176||See text|
|AFM13||Affimed||R/r CD30+ve peripheral T-cell lymphoma||Ph2 Redirect||107||NK cell-engaging bispecific, basis of accelerated approval filing (AACR 2022 – Affimed shows that 2021 was no fluke)|
|Zanidatamab||Zymeworks||2L+ biliary tract cancer||Pivotal Herizon-BTC-01||48||Biparatopic HER2-targeted antibody drug conjugate|
|Novo Nordisk (Forma)||Sickle cell disease||Ph2/3 Hibiscus interim by YE, will reveal the dose to be used in Ph3 portion||-||PKR activator, Forma acquired by Novo for $1.1bn (Novo’s $1.1bn pro Forma deal)|
|Obesity||Ph2||-||Long-acting GLP-1/Glu agonist, showed dose-relationship on HbA1c and weight loss, with tolerability issues|
|Lacutamab||Innate||Sézary syndrome & mycosis fungoides in patients with KIR3DL2+ve tumours||Ph2 Tellomak||-||Data could inform much larger indication, peripheral T-cell lymphoma; about half of these tumour types are KIR3DL2+ve|
|*SBI as general liver disorder. Source: Evaluate Pharma, company releases & clinicaltrials.gov.|