Heading into 2021, Biogen will report data from pipeline assets but the areas involved − gene therapies and neurodegenerative diseases − are often linked with clinical setbacks.
Lilly, meanwhile, will share further phase III data from its vast clinical programme with tirzepatide in type 2 diabetes, and Bristol’s Tyk2 inhibitor deucravacitinib has a second late-stage trial in play.
Looking beyond Biogen’s controversial Alzheimer’s drug aducanumab, which has a Pdufa date of March 5, four of the company's projects are due to yield data in the first half of next year.
Cinpanemab is an anti-alpha synuclein MAb, and phase II data in Parkinson’s disease are due early next year. The primary endpoint of the Spark study is MDS-UPDRS total score, a measure of impairment and disability, versus placebo.
On the competition front, Roche and Prothena’s similarly acting prasinezumab failed to beat placebo on MDS-UPDRS total score in the phase II Pasadena study in early Parkinson’s disease. However, signs of efficacy on motor symptoms pushed the companies into committing to a confirmatory phase 2b study.
Another of Biogen’s MAbs, gosuranemab, is set to report data in early Alzheimer’s disease. The primary outcome of the Tango study is safety but secondary measures include the clinical dementia rating scale.
The anti-tau project failed last year in progressive supranuclear palsy which, like Alzheimer's, is characterised by the build-up of tau in the brain. More recently Roche and AC Immune’s anti-Tau MAb semorinemab failed in prodromal to mild Alzheimer’s; data presented at the CTAD conference in November from the Tauriel study showed that semorinemab did not slow tau accumulation in the brain versus placebo.
This prompted analysts to question whether a product specific problem caused the trial miss, rather than the Tau hypothesis being a dud. Many believe that targeting Tau holds promise, and positive signals with gosuranemab would help.
Meanwhile, data are also expected on two gene therapies that focus on rare eye diseases, gained through Biogen’s $877m acquisition of Nightstar in 2019. Timrepigene emparvovec is in phase III for choroideremia, while BIIB112 is expected to yield phase II/III data in X-linked retinitis pigmentosa.
The primary endpoint for the Star study in choroideremia is best corrected visual acuity (BCVA) at 12 months. Two doses, injected subretinally, are being tested versus placebo.
Timrepigene is designed to allow expression of functional REP1 protein, which plays a role in intracellular protein trafficking and the elimination of waste products from retinal cells. Biogen looks to have the most advanced gene therapy here while Roche has two candidates − RG6367 in phase I/II and RG6247 in phase I.
Lastly, data from BIIB112’s Xirius study is expected. The phase II/III trial compares two doses with placebo, and efficacy measures include BCVA. Results from the phase I dose escalation portion showed a lack of efficacy in patients given lower doses, and inflammation issues in the higher-dose cohorts that appeared to blunt efficacy.
All four assets have yet to attract sizeable sales forecasts from the sellside, highlighting the perceived risk involved. Biogen recently shelled out $1.5bn for two of Sage’s neurology assets and, with the approval fate of aducanumab still a big unknown, the company needs its thin pipeline to start delivering.
Diabetes and beyond
Eli Lilly is targeting type 2 diabetes with the dual GIP/GLP-1 agonist tirzepatide. Data from Surpass-1, in diabetes not controlled with diet and exercise, showed no serious safety signals but efficacy missed the top end of expectations (Lilly’s new diabetes project looks good, but not knockout, December 10, 2020).
The first half of 2021 will see three more studies report, this time against active comparators and placebo in Surpass-2, 3 and 5 (Tirzepatide’s time to shine for Lilly, February 4, 2020).
Something to watch out for will be tolerability, Lilly had to develop a dose titration schedule to manage nausea, vomiting and diarrhoea.
Lilly and Boehringer Ingelheim’s older diabetes project Jardiance is hoping to expand into heart failure with preserved ejection fraction (HFpEF), a disease without any approved treatments.
The composite primary endpoint of Jardiance’s Emperor-Preserved study is cardiovascular death or hospitalisation, versus placebo. The SGLT2 met the same endpoint in patients with reduced ejection fraction in the Emperor-Reduced study.
Astrazeneca’s own SGLT2 Farxiga is already on the market for reduced ejection fraction but its equivalent trial in preserved ejection patients called Deliver is still recruiting and will likely read out towards the end of 2021.
Novartis might, however, beat both products to the punch. The company’s angiotensin receptor-neprilysin inhibitor Entresto will be reviewed by an FDA advisory committee this week, and even though the drug's own HFpEF trial missed its primary endpoint, briefing notes released ahead of the hearing suggest that the regulator favours approval.
And the rest
Bristol’s oral Tyk2 inhibitor deucravacitinib has already performed well in phase III and a second pivotal study in psoriasis, Poetyk-PSO-2, is expected in the first quarter of next year. Topline data from Poetyk-PSO-1 showed the drug not only beating placebo, but also Otezla, another oral drug; detailed data are yet to be presented, however.
The psoriasis pipeline is dominated by biologics, but Bristol believes that that in deucravacitinib it has the best-in-class oral drug, with potential for biological-like efficacy with convenient administration. But Bristol is not alone, phase II psoriasis data from Pfizer's own Tyk2 inhibitor PF-06826647 are due early next year.
The table below contains a fuller list of upcoming catalysts with consensus forecasts from EvaluatePharma.
|Q1 2021 clinical catalysts (excludes Covid-19 data)|
|Project||Company||Therapy area||Q1 clinical catalyst||2026e indication sales ($m)||Note/ Vantage coverage|
|Tirzepatide||Eli Lilly||Type 2 diabetes||Ph3 Surpass-2 (vs Ozempic), 3 (vs Tresiba), 5 (vs placebo) expected H1 2021||3,153||See text|
|Deucravacitinib (BMS-986165)||Bristol Myers Squibb||Psoriasis||Phase 3, Poetyk-PSO-2 data vs placebo & vs Otezla||1,868||See text|
|Gilead||Diffuse large B-cell lymphoma||Zuma-7, versus SOC, data 2021||1,386||Seeks to expand Yescarta’s lymphoma use from third to second line|
|Jyseleca (filgotinib)||Gilead/Galapagos||Safety study||Manta and Manta-Ray studies, examining testicular toxicity, due H1||872||CRL in RA in August 2020, FDA requested safety data|
|Sotorasib||Amgen||NSCLC||Ph2 Codebreak 100 expected at World Lung conference (Jan 28-31, Jan 12 for embargoed abstracts)||867||Positive top line data showed response rates consistent with phase I; these showed a 35% ORR and a median duration of response of 10.9 months|
|Tominersen (RG6042/Ionis-HTTRx)||Roche/Ionis||Huntington's disease||Phase 1/2a OLE studies and natural history studies||560||HTT antisense, updated data from the open-label extension studies, biomarker data from Uniqure's AMT-130 expected Q2/3 (AAV-delivered RNAi)|
|PF-06826647||Pfizer||Psoriasis||Ph2||512||A Tyk2 inhibitor like Bristol's deucravacitinib|
|177Lu-PSMA-617||Novartis||mCRPC 3L||Vision Ph3, expected H1, event driven trial||327||Ph3 adding 177Lu-PSMA-617 to SOC, Ph2 (vs. cabazitaxel) showed significantly greater % of patients treated with '617 had a PSA decline ≥ 50% (Asco 2020)|
|Eli Lilly||Early symptomatic Alzheimer's disease||Ph2 Trailblazer-Alz||78||Binds to pGlu-Abeta, which is involved in the formation of toxic oligomers (aducanumab's Pdufa date is March 5, 2021)|
|Biogen||Choroideraemia (X-linked retinal degeneration)||Ph3 Star H1||71||See text|
|BIIB112||Biogen||X-linked retinitis pigmentosa||Ph2/3 Xirius H1||33||See text|
|BIIB054 (cinpanemab)||Biogen||Parkinson's disease||Ph2 Spark H1||25||See text|
|BIIB092 (gosuranemab)||Biogen||Mild cognitive impairment due to Alzheimer's disease or with mild AD||Ph2 Tango H1||21||See text|
|Jardiance||Boehringer Ingelheim/Eli Lilly||Heart failure with preserved ejection fraction (HFpEF)||Emperor-Preserved||-||See text|
|Bintrafusp Alfa||GSK/Merck KGaA||1L biliary tract cancer||Pivotal H1||-||Anti-PD-L1/TGF-β fusion protein, plus SOC vs placebo + SOC|
|Ilaris (canakinumab)||Novartis||2L/3L NSCLC||Ph3 Canopy-2 H1||-||Plus docetaxel vs placebo + docetaxel, (1L study Canopy-1 final readout H2)|
|Entresto||Novartis||Post-acute myocardial infarction||Ph3 Paradise-MI H1||-||Primary measure: time to the first occurrence of a confirmed composite endpoint (CV death, heart failure hospitalisation, or outpatient heart failure)|
|Sources: EvaluatePharma, company releases, analyst notes, clinicaltrials.gov|