Big pharma’s key catalysts in the second quarter

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.

Chasing Waterfalls

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.

Amcenestrant has demonstrated activity in heavily pretreated patients: last year, the phase 1/2 Ameera-1 study found an objective response rate of 8.5%.

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.