Merck gets a much-needed win
But can sotatercept go the (six-minute walk) distance?
Merck & Co believes that its pulmonary arterial hypertension project sotatercept is a potential blockbuster, albeit a slow burn in terms of sales. That smouldering could get started fairly soon: today the company top-lined the pivotal Stellar trial as a hit.
Sotatercept was the main reason behind Merck’s $11.5bn purchase of Acceleron last year, so the win has come as a huge relief, with the group’s stock ticking up 4% in early trade. But investors might be wise to wait for the actual figures from Stellar before popping the champagne.
Stellar tested sota on top of standard background therapy. It used improvements in six-minute walk distance as the primary endpoint, with Merck stating that the activin receptor type IIA-Fc fusion protein produced a statistically significant and clinically meaningful improvement over placebo.
In the phase 2 Pulsar study sotatercept produced marked improvements in six-minute walk distance, and investors will be hoping for similar signs of efficacy in Stellar.
| Pulsar (NCT03496207) results | |||
|---|---|---|---|
| Endpoint | Sotatercept 0.3mg/kg (N = 32) |
Sotatercept 0.7mg/kg (N = 42) |
Both sotatercept dose groups (N = 74) |
| Pulmonary vascular resistance (dyne-second per cm5)* | |||
| Least‑squares mean difference as compared with placebo | -145.8 | -239.5 | -198.9 |
| P value vs pbo | 0.003 | <0.001 | |
| 6‑minute walk distance (m) | |||
| Least‑squares mean difference as compared with placebo | 29.4 | 21.4 | 24.9 |
| *Primary endpoint. Source: NEJM. | |||
Pulsar’s primary endpoint, also hit, was pulmonary vascular resistance, the leading cause of pulmonary hypertension. Vascular resistance was also hit in Stellar, but more importantly so was another secondary, the time to death or the first occurrence of a clinical worsening event.
As a hard endpoint this is crucial in itself, but it is also a good sign for the other PAH sotatercept trials Merck is running. Hyperion, in newly-diagnosed patients, uses this as its primary outcome, and Zenith, in severely ill patients at high risk of mortality, uses a similar measure.
| Top-line Stellar results | |
|---|---|
| Endpoint | Result |
| 6‑minute walk distance* | Hit |
| Time to death or the first occurrence of a clinical worsening event (TTCW) | Hit |
| Multicomponent improvement from baseline** | Hit |
| Change from baseline in pulmonary vascular resistance | Hit |
| Change from baseline in NT-proBNP levels | Hit |
| Proportion of participants who maintained or achieved a low risk score using the simplified French risk score calculator | Hit |
| Change from baseline in the physical impacts domain score of PAH | Hit |
| Change from baseline in the cardiopulmonary symptoms domain score of PAH-Sympact | Hit |
| Change from baseline in the cognitive/emotional impacts domain score of PAH-Sympact | Missed |
| *Primary endpoint. **Defined as improvement in 6MWD, improvement in NT-proBNP level, and either improvement in WHO FC or maintenance of WHO FC II. Source: company release. | |
Safety was consistent with Pulsar, Merck said, which previously raised few serious concerns.
Oom-Pah-Pah
Merck says it is “moving with urgency” to get the drug filed with regulators. The question is what the data might mean for sota’s commercial prospects.
There are plenty of PAH products on the market but these simply act as vasodilators, failing to address the stiffening of the blood vessel walls that causes the hypertension in the first place. To hear Merck tell it, sotatercept is on course to be the first disease-modifying therapy.
Mizuho analysts estimate risk-adjusted sales of $700m five years after launch, rising to around $2bn in 2033 should the other studies come in positive and lead to subsequent approvals. Evaluate Pharma's sellside consensus sits at sales of $656m in 2028.
Sota will need to beat these numbers to help justify Merck’s move on Acceleron.
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