Ash 2021 preview – small increases and big falls

The early movers could point to a disappointing meeting.

Yesterday’s release of this year’s crop of Ash abstracts seems to have prompted more fallers than risers in terms of share price activity. Sanofi’s fitusiran, one of the projects that the French group admitted last week would be set back 18 months or so, should draw attention with data from one of its suite of phase 3 haemophilia studies.

More dramatic moves – and not in the right direction – occurred for ALX Oncology and Syndax Pharmaceuticals. Perhaps the situation for these groups will improve with the actual presentations, which will be given in just over a month’s time. 

Sanofi scored a plenary session with new data from the Atlas-INH study, which tests the ability of the siRNA agent fitusiran, licensed from Alnylam, to prevent bleeds in patients with haemophilia A or B who have inhibitors.

Efficacy does not seem to be a problem; the study hit statistical significance for the primary and secondary endpoints, fitusiran reducing the annualised rate of all bleeds, spontaneous bleeds and joint bleeds versus on-demand bypassing agents, the therapies used to treat haemophilia patients with high levels of inhibitors.

25 patients in the fitusiran cohort – 65.8% – had no treated bleeding events, and patients with both the A and B forms of the disease benefited.

Bleeding events in Atlas-INH 
  Fitusiran 80mg prophylaxis (n=38) BPA on demand (n=19)
All treated bleeds
Estimated ABR 1.67 18.07
P value <0.0001  
Treated spontaneous bleeds
Estimated ABR 0.87 15.68
P value <0.0001  
Treated joint bleeds
Estimated ABR  1.35 13.76
P value <0.0001  
ABR = annualised bleeding rate. BPA = bypassing agents. Efficacy period is from day 29 to day 246 or the last day of bleeding follow-up, whichever is the earliest. Source: Ash abstract #4.

But it is safety that is the big question with fitusiran, and here the picture is murky, though not disastrous.

Almost all the patients in the fitusiran arm had at least one treatment-emergent adverse event, with 92.7% having side-effects versus 57.9% in the bypassing agent arm. 13 treatment-emergent serious adverse events (TESAEs) were reported in seven patients (17.1%) in the fitusiran arm, versus eight TESAEs in five control patients (26.3%). 

TESAEs in the treatment arm included thrombosis, and one patient in the fitusiran arm exited the trial owing to non-serious side effects – spinal vascular disorder and thrombosis.

Still, these data come from fitusiran’s original dosing regimen of 80mg once a month. Sanofi is now investigating a lower dose and less frequent administration, and this is what prompted the delay in filing, from next year to 2024 (Delays hit Sanofi, October 28, 2021). 

Elsewhere an abstract on Keros Therapeutics’ a modified activin receptor type IIA inhibitor KER-050 in myelodysplastic syndromes helped the group’s stock climb 28%. In 10 evaluable participants overall erythroid response rate was 60%, and four of seven achieved transfusion independence.


Last year IGM Biosciences’ anti-CD20 bispecific IGM-2323 was the subject of a limp abstract detailing just two partial responses, but the company ultimately managed to escape a bloodbath (IGM averts disaster, but competition looms, December 7, 2020). Yesterday an Ash abstract detailing the trial's update caused an initial 16% fall, before IGM closed down just 2%.

The abstract shows eight of 23 evaluable patients responding – a surely uncompetitive 35% overall response rate versus prior data on other anti-CD20 bispecifics in non-Hodgkin lymphoma. Still, the very early April data cutoff will have investors hoping for much more to be unveiled at Ash in December, 

Global Blood also fell and then recovered, its initial slide of 9% turning into a 2% loss at close. Its next-generation sickle haemoglobin polymerisation inhibitor GBT021601 showed haemoglobin occupancy of up to 25%, versus a previously hoped for haemoglobin modification of 30-40%; occupancy has been shown to correlate with modification.

However, the abstract only concerns volunteer single-dose data; the conference itself will have multi-dose data in actual patients, so the hope is that the data will improve.

ALX Oncology tanked 15% on data in myelodysplastic syndrome that put its CD47 inhibitor evorpacept (ALX148) some way behind magrolimab, the rival asset Gilead acquired via Forty Seven. In the phase 1/2 Aspen-02 trial evorpacept plus azacytidine mustered ORRs of 60% in all-comers and TP53-mutated disease, behind magrolimab's corresponding 91% and 75% respective ORRs on a cross-trial basis.

And Syndax dropped 16% on data from the phase I/II Augment-101 study of the menin inhibitor SNDX-5613 in patients with mutant relapsed/refractory acute leukaemia with MLL-rearrangements (MLLr) or NPM1 mutations. The composite complete response rate was 44%. The data are important for investors in Kura, whose rival menin inhibitor KO-539 does not feature at Ash.

The Ash conference is due to take place virtually, and in person, on December 11-14 in Atlanta, Georgia.

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