Biotech’s important clinical data readouts

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.

RNAi

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.

Collaboration

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.