Biotech’s important clinical data readouts

The second quarter brings updates for Scholar Rock, Alnylam and Dicerna, among others.

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.

Targeting myostatin

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)

Loncastuximab tesirine
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
Camidanlumab tesirine
(Cami, ADCT-301) 
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 &

Share This Article