The second quarter is gearing up to be important for Biogen: its Alzheimer's asset aducanumab is due a US approval decision, and clinical data from two projects will show whether the company was right to hand over $1.5bn to Sage at the end of last year.
Meanwhile, data with Sanofi’s oral selective oestrogen receptor degrader will need to be good enough for a filing if the company is to get a jump on the competition.
The most important asset in Biogen’s deal with Sage is zuranolone, and data are expected in the second quarter from the Waterfall study in major depressive disorder.
Zuranolone has already failed one phase 3 depression trial, Mountain, but a couple of differences in Waterfall could mean a different outcome.
First, Mountain had tested 20mg and 30mg doses of zuranolone, while Waterfall evaluates 50mg. And Mountain enrolled patients with baseline Ham-D scores of 22 or more, while Waterfall looks at more severe patients, those with a Ham-D score of at least 24. The primary endpoint of Waterfall is the same as Mountain: change from baseline in Ham-D score at day 15.
Sage bulls will hope that data released last week from a separate study, Shoreline, bode well for the outcome of Waterfall. Shoreline, an open-label study evaluating zuranolone as an as-needed therapy for major depressive disorder, tested both 30mg and 50mg, and the 50mg dose looked slightly more efficacious. Still, baseline Ham-D scores in Shoreline were 20 or above, making it difficult to read across from that study.
The second asset included in the deal, Sage-324, also has data next quarter, from the phase 2 Kinetic study in essential tremor. Sage hopes to see a 30-50% reduction in tremors after 28 days' treatment with Sage-324 dosed at 60mg per day versus placebo.
A phase IIb trial is expected to start later in the year to explore dosing.
First to market?
A four-way battle is under way between Roche, Astrazeneca, Radius Health and Sanofi to get an oral selective oestrogen receptor degrader (Serd) to market for Her2-negative, ER-positive breast cancer.
Data are expected soon from Sanofi’s pivotal Ameera-3 study of amcenestrant in second/third-line patients, and the company could file based on these. The phase 2 study tests daily amcenestrant versus hormone therapy, with a primary endpoint of PFS; OS is a secondary measure.
According to Jefferies analysts, the primary opportunity for an oral Serd would be as a replacement for Astrazeneca’s Faslodex, which has a second-line label. That drug's commercial potential was held back by its intramuscular delivery and poor bioavailability, but Faslodex sales still topped $1bn in 2018, the year before its patent expired.
Analysts are assigning bold values for oral Serds: Jefferies estimates “at least a $7-8bn market”, while Evercore puts it at “a $10bn+ opportunity, similar to the CDK4/6 inhibitors”, with use in metastatic and potentially even adjuvant settings.
Investors have a while to wait for first-line data: Sanofi’s phase 3 Ameera-5, which tests amcenestrant in combination with Ibrance, has a primary completion date in 2024. Astrazeneca’s camizestrant and Roche’s giredestrant both also recently started front-line studies in combination with Ibrance.
The table below contains a fuller list of upcoming catalysts with consensus forecasts from Evaluate Pharma.
|Q2 2021 clinical catalysts (excludes Covid-19 data)|
|Project||Company||Therapy area||Q2 clinical catalyst||2026e indication sales ($m)||Note/Vantage coverage|
|Tirzepatide||Lilly||Type 2 diabetes||Ph3 Surpass-3 (vs Tresiba), 5 (vs placebo)||3,778||Surpass-2 (versus Ozempic) recently hit (Lilly’s tirzepatide Surpasses Novo’s Ozempic)|
|Zuranolone (Sage-217)||Biogen/ Sage/ Shionogi||Major depression||Topline data from Waterfall||2,174||See text|
|Finerenone||Bayer||CKD and type 2 diabetes||Ph3 Figaro-DKD||834||Filed in US on basis of ph3 Fidelio-DKD study, but could struggle commercially (Bayer faces an uphill fight with finerenone)|
|Libtayo||Sanofi/ Regeneron||1L NSCLC||Ph3 chemo combo in PD-L1 <50% expressers (part 1)||746||Approved in PD-L1-high patients in Feb; if approved in PD-L1-low Libtayo would still face an entrenched competitor (Keytruda)|
|Lebrikizumab||Lilly/ Almirall||Atopic dermatitis||Pivotal ph 3 Adcovate1 & Advocate2||725||Anti-IL13 MAb; safety & efficacy bar set high here by Dupixent|
(TAK-924) +/- azacitidine
|Takeda||High-risk myelodysplastic syndromes||Ph3 Panther||594||First-in-class NEDD8-activating enzyme inhibitor, aims to improve on Vidaza; ph2 reported at Asco 2020|
|Sanofi||2/3L breast cancer||Pivotal data from Ameera-3||492||See text|
|Anifrolumab||Astrazeneca||Lupus nephritis||Ph2 Tulip-LN1||488||Filed in SLE|
|Domvanalimab + zimberelimab +/- etrumadenant||Arcus||1L NSCLC||Ph2 Arc-7||309 (combined sales)||If this proves competitive Gilead could exercise opt-in rights for domvanalimab, an anti-Tigit MAb|
|Relatlimab||Bristol Myers Squibb||1L melanoma||Ph3 Opdivo combo vs Opdivo||306||
Anti-Lag 3 MAb, possible lower-tox replacement for Yervoy
|Sage-324||Biogen/ Sage||Essential tremor||Ph2 Kinetic||115||See text|
|GSK||1L HNSCC, relapsed NSCLC||Ph2 Induce-3 interim combo with Keytruda; ph2 Entrée + docetaxel vs docetaxel||94||Jounce had issues with its Icos inhibitor in Nov; Glaxo claims its project is differentiated as it causes no or minimal T-cell depletion (Jounce trounced after Icos stumble)|
|Biogen||Choroideraemia (X-linked retinal degeneration)||Ph3 Star||71||Gene therapy (Big pharma catalysts to ring in the new year)|
|Abbvie||Alzheimer's||Ph2 mid year||53||Anti-tau MAb, failed in progressive supranuclear palsy (Roche and AC Immune’s semorinemab failed in Alzheimer's last year)|
|BIIB112||Biogen||X-linked retinitis pigmentosa||Ph2/3 Xirius||33||Gene therapy (Big pharma catalysts to ring in the new year)|
|Biogen||Alzheimer's||Ph2 Tango||21||Anti-tau MAb, failed in progressive supranuclear palsy (Roche and AC Immune’s semorinemab failed in Alzheimer's last year)|
|Novo Nordisk||Haemophilia A||Ph 1/2 Frontier1||14||Next-generation FVIII mimetic, Mim8, is a bispecific antibody for SC prophylaxis|
|Abbvie/ J&J||1L CLL||Ph3 Glow and Gaia/CLL13 (investigator initiated)||-*||Gaia is a chemo-free front-line setting for patients without 17p deletion|
|PR001||Lilly||Parkinson's with GBA1 mutation||Propel Ph1/2 biomarker and safety analysis year||-||AAV GBA1 gene therapy, gained through Lilly's acquisition of Prevail|
|Entresto||Novartis||Post-acute myocardial infarction||Ph3 Paradise-MI May 15, ACC||-||Entresto recently gained approval in HFpEF; Paradise-MI data could add another 800,000 US patients per year (New US nod widens the net for Entresto)|
|Jardiance||Lilly||HFpEF||Ph3 Emperor-Preserved||-||Composite primary endpoint is CV death or hospitalisation, vs placebo|
|Hepcludex||Gilead||Hepatitis D||Ph3 MYR 301 due H1||-||
Gilead bought Myr in Dec for $1.4bn; ph3 is to serve as the basis for filing Hepcludex in the US; conditionally approved in EU
|*Already on the market in the indication (at different treatment line). Sources: EvaluatePharma, company releases, analyst notes & clinicaltrials.gov.|