Previously Evaluate Vantage delved into key big pharma data reveals; here, we take a look at the clinical results due for biotech companies with a market cap of $1bn and above.
Scholar Rock will be hoping to improve on earlier positive data with apitegromab in spinal muscular atrophy, while cardiac biomarkers will be key to Alnylam’s update on vutrisiran. Meanwhile, Dicerna hopes to target all forms of primary hyperoxaluria with nedosiran.
Scholar Rock’s apitegromab is a selective inhibitor of the activation of latent myostatin, and is designed to increase muscle mass in patients with SMA.
A 12-month cut of the phase 2 Topaz study is due next quarter, and results will need at least to maintain the motor function improvements observed at six months, if not continue to improve on them. At that point a mean 2.4-point improvement in HFMSE, an assessment of motor function, was seen with 2mg/kg apitegromab IV, and a 5.6-point improvement with 20mg/kg. Apitegromab was administered on top of Biogen’s Spinraza to a cohort comprising 18 non-ambulatory type 2 SMA patients with a mean age of four.
An improvement of more than three points is considered highly meaningful, and the six-month data caused Scholar’s shares to rocket 119% last October. The company is now worth over $2bn.
The approved SMA therapies – Spinraza, Zolgensma and Evrysdi – all target the underlying cause of SMA, and increase production of the survival motor neurone protein. Apitegromab is intended to be used on top of these existing options in most cases. The design of apitegromab's phase 3 trial, which is expected to start later this year, is also of interest.
Alnylam toplined positive data from the Helios-A trial earlier this year, and full data are expected on April 19 at the American Academy of Neurology meeting. Vutrisiran, an RNAi therapeutic, met all primary and secondary endpoints at nine months in patients with hereditary ATTR amyloidosis with polyneuropathy.
Detailed efficacy and safety data will allow comparisons against Alnylam’s own Onpattro, which is sold for the polyneuropathy subtype of the disease and given as IV. Vutrisiran is given subcutaneously and so could be more convenient.
Further details are also awaited to gauge vutrisiran's chances in the cardiomyopathy amyloidosis subtype, a much larger setting. All Alnylam has said so far is that improvements were seen on the cardiac biomarker NT-proBNP.
Pfizer’s competing project Vyndaqel/Vyndamax, an oral drug, has a broad label in the US, including cardiomyopathy, but is restricted to polyneuropathy outside the US. Pfizer's therapy is forecast to be market leader by 2026 with global sales of $4.2bn, according to Evaluate Pharma, while vutrisiran takes second place with $1.5bn.
Turning to another RNAi project, Dicerna’s nedosiran, two studies are expected to report in primary hyperoxaluria (PH), an ultra-rare disorder that causes complications in the kidneys. Prevalence of the disease is estimated at around two cases per million, and there are three types, differing in severity and genetic cause.
Type 1 is the most severe and most common, estimated to account for 70-80% of all diagnosed patients, while type 3 is typically less damaging and rarely requires clinical intervention.
Dicerna’s pivotal phase 2 study, Phyox2, compares nedosiran with placebo in 36 patients with either PH1 or PH2. The primary measure is the percentage change from baseline in 24-hour urinary oxalate excretion, measured at three, four, five and six months to give an average value over time.
Alnylam’s Oxlumo, another RNAi-based therapy, was approved late last year in PH1 patients only. The Illuminate-A study in 39 patients showed a mean 65% decrease from baseline in 24-hour urinary oxalate in the Oxlumo group compared with a 12% drop in the placebo group (p<0.0001).
Nedosiran is at least a year and a half behind Oxlumo, but Dicerna is trying to tie up all types of PH. The company hopes to file an NDA for nedosiran in the third quarter in PH1 and PH2. A separate trial called Phyox4 is aimed at PH3; results are due mid-year and could form the basis of an accelerated approval.
2026 sales of nedosiran are forecast to reach $376m, higher than Oxlumo’s $273m, according to Evaluate Pharma consensus. However, a non-exclusive IP cross-licensing agreement, announced last year, means that each company will benefit from the other's success.
The table below contains a fuller list of upcoming catalysts with consensus forecasts from Evaluate Pharma. A look at big pharma clinical catalysts can be found here.
|Q2 clinical catalysts (excludes Covid-19 data)|
|Project||Company||Therapy area||Q2 clinical catalyst||2026e indication sales ($m)||Note/Vantage coverage|
|Vutrisiran||Alnylam||ATTR amyloidosis||Ph3 Helios-A full 9mth results at AAN (Apr 19, 14.00 EDT)||1,470||See text|
|CTX001||Vertex/Crispr||Beta-thalassemia, sickle cell disease||2021 updates ph1/2 Climb-Thal-111 in beta-thalassemia & Climb-SCD-121 in SCD||1,345||Promising early data (Ash 2020 – Crispr gets another boost)|
|SRP-9001||Sarepta/Roche||Duchenne muscular dystrophy||Open-label ph2 Study 103 Endeavor, biomarker and safety||1,033||Gene therapy, Study 102 (placebo controlled) failed in Jan (Gene therapy trial fails to rectify Sarepta’s sorry record)|
|ADC Therapeutics||r/r DLBCL||Updated ph1 Lotis-3 + ibrutinib||1,025||Pdufa in May as a monotherapy in 3L+ r/r DLBCL, early data from Lotis-3 at Ash 2020 were underwhelming|
|Cabometyx||Exelixis||Hepatocellular carcinoma||Ph3 Cosmic-312 1L + Tecentriq||667*||Label expansion|
|Mirvetuximab soravtansine||Immunogen||Ovarian & endometrial cancers||Ph1b mature data Forward II at Asco (Avastin combo)||572||Forward I study failed (monotherapy), key catalyst will be Soraya study in FRα-high in Q3 (A delicate balancing act for Immunogen)|
|SRK-015 (apitegromab)||Scholar Rock||Types 2 & 3 spinal muscular atrophy||Topaz ph2, topline 12 month data||505||See text|
|EDP-305||Enanta||Nash||Interim Argon-2 mid year (1.5 & 2mg)||497||Argon-1 showed 1mg was not efficacious; 2.5mg was efficacious but caused unacceptable pruritus (Enanta fails to convince with Nash win)|
|APL-2 (systemic pegcetacoplan)||Apellis||PNH||Ph3 Prince||445||Treatment-naive study, Pdufa in May|
|Nedosiran||Dicerna||Primary hyperoxaluria||Pivotal ph2 Phyox2 (PH1 and PH2 patients), topline Phyox4 (PH3) mid year||376||See text|
|RP-L102||Rocket||Fanconi anaemia||Further updates from ph1 Process B||332||Gene therapy, early data at Ash 2020 (Ash 2020 preview – late-breaker puts Uniqure in pole position)|
|SER-287||Seres||Ulcerative colitis||Ph2b Eco-Reset mid year||310||Could serve as one of two required pivotal trials supporting a filing|
|Macrogenics||1L Her2+ gastric cancer||Ph2/3 Mahogany first 40 patients in Module A (+ anti-PD-1 retifanlimab) at Asco||120||Enrolment of Module B (+ retifanlimab and chemotherapy) ongoing|
|ADC Therapeutics||Relapsed or refractory Hodgkin lymphoma||Pivotal ph2 interim H1||111||Trial resumed in Jun 2020 after a clinical hold was lifted; two patients had been diagnosed with Guillain–Barré syndrome|
|MGC018||Macrogenics||Advanced solid tumours||Updated ph1 dose escalation & expansion at Asco (mCRPC and NSCLC cohorts)||88||B7-H3-targeting antibody drug conjugate|
|RP-L201||Rocket||Leukocyte adhesion deficiency-I||Ph2||66||Gene therapy, early data at Ash 2020 (Ash 2020 preview – late-breaker puts Uniqure in pole position)|
|Cytokinetics||Hypertrophic cardiomyopathy||Ph2 Redwood-HCM (data from both cohorts)||43||Positive interim data in Dec; cardiac myosin inhibitor like Myokardia's mavacamtem; Bristol bought Myokardia for $13.1bn|
|VX-864||Vertex||Alpha-1 antitrypsin deficiency||Ph2 H1||-||Z-AAT corrector said to be structurally distinct from discontinued VX-814|
|Rexulti||Lundbeck/ Otsuka||Agitation associated with Alzheimer's||Ph3 interim||-||Already on the market for major depressive disorder and schizophrenia|
|Ionis-GHR-LRx||Ionis||Acromegaly||Ph2||-||Growth hormone receptor antisense to decrease the circulating level of insulin-like growth factor-1|
|Ionis-PKK-LRx||Ionis||Hereditary angioedema||Ph2||-||Prekallikrein antisense|
|Ionis-ENAC-2.5Rx||Ionis||Cystic fibrosis||Ph2a data expected at ATS (May 14-19)||-||Inhaled epithelial sodium channel antisense; Translate Bio's inhaled mRNA recently failed in CF, Arrowhead's ARO-ENaC will report early data mid year (Translate’s investment case shifts fully to Covid-19)|
|GLPG3970||Galapagos||Ulcerative colitis, RA, psoriasis||Ph2 Ladybug (RA), Sea Turtle (US), ph1 Calasoma (psoriasis)||-||Part of Toledo programme (Gilead’s Galapagos hopes now rest on Toledo)|
|Lemzoparlimab||I-Mab Biopharma /Abbvie||AML/MDS||Ph1 China trial||-||Abbvie licensed the project last year for $200m up front (Abbvie looks east for CD47)|
|KarXT||Karuna Therapeutics||Dementia-related psychosis||Cohort 3 ph1b elderly healthy data||-||Encouraging preliminary data with first two cohorts released in Feb|
|CLN-081||Cullinan Oncology/ Zai Lab||NSCLC (EGFR exon 20 insertion mut)||Ph1/2 potentially at Asco||-||CLN-081 needs to show competitive efficacy and better tolerability vs Takeda's mobocertinib & J&J's amivantamab|
|NGM Bio||Nash with stage 2 (F2) or F3 liver fibrosis||Ph2b Alpine 2/3||-||Once-daily FGF19 regulator; ph2 biopsy data showed 22% of treated subjects had fibrosis improvement and Nash resolution|
|RP2||Replimune||Solid tumours||Ph1 combination with Opdivo likely at Asco||-||Encouraging earlier results with monotherapy (SITC 2020 – embargo snafu triggers the first movers)|
|KER-050||Keros Therapeutics||Anaemia & thrombocytopenia in MDS||Ph2 data due mid year (RS+ and RS- patients)||-||$110m IPO Apr 2020, potential differentiation vs Bristol's Reblozyl that is only approved in ring sideroblast-positive patients|
|PBGM01||Passage Bio||GM1 gangliosidosis||Ph1/2 Imagine-1 biomarker and safety data mid year||-||Gene therapy (A three-way battle beckons in GM1 gangliosidosis)|
|*Already on the market in the indication (at different treatment line). Sources: EvaluatePharma, company releases, analyst notes & clinicaltrials.gov.|