Op-ed: What we’re watching closely as an unusual #ASH21 kicks off in Atlanta
Remember when medical meetings were live and in person?
Stepping off the plane from Austin into this year’s American Society of Hematology annual meeting in Atlanta, I can’t help but feel some of the excitement and sense of intellectual ferment we used to feel around the biggest conferences of the year — but it’s undeniable this year is different.
No longer restricted to a wonky Internet platform, #ASH21 has adopted a live-virtual hybrid model, and I embraced the chance to return to my first live meeting in roughly two years — vaxxed, boosted and masked, of course. It’s good to be back, but I, like the rest of the world, am still adjusting to the new normal.
Where before my weekend might be packed with sidebars with biopharma executives shared over lukewarm cups of coffee from the media room, quick meet-and-greets with fellow journos and PR flacks, and wolfing down a sandwich from the buffet bar, this year’s event already feels more muted and a little more somber.
The coffee and sandwiches still flow freely, and a couple of folks are still braving a short sitdown and introduction, but most of my calls have already happened this week on the now-familiar confines of Zoom and Microsoft Teams. So where some of the excitement is gone, this meeting has also given me some time ahead to reflect on what is still a fascinating time in hematology.
In conversation with more than a dozen biopharma execs and researchers, I’ve compiled a bit of a self-guide to some of the biggest trends and abstracts expected at this year’s #ASH21. Many of the biggest names in this space are certainly throwing their weight around, but there are still a few undertold stories floating around out there that are worth watching.
If you’re comfortable at home in your PJs or cramming yourself into suddenly too-small work clothes in Atlanta (paging: me), I hope you enjoy my list of what I’m watching this weekend.
As current-gen CAR-T scours for more patients, a spate of next-gen drugs vie for a breakthrough
Earlier today, Bristol Myers Squibb and Gilead’s Kite read out competing data for their current-gen CAR-Ts in second-line B cell lymphoma as head-to-head challenges to an ugly standard of care.
Those readouts are big news in that they represent a big advance for the current generation of CAR-Ts — with onerous safety profiles and the weight of the unknown on their shoulders — looking to break new ground in earlier lines of therapy. And this isn’t the end for those ambitions, either. Kite is also presenting more data for Yescarta in first-line, high-risk LBCL patients on Monday, which will be something to watch not only for intermediate efficacy markers but also whether physicians will be able to stomach a cell therapy so early in the treatment paradigm.
That battle may come down to safety, where Bristol Myers’ Breyanzi appears to show a safer profile over Kite’s rival. Time will tell on whether that gap holds up.
But as the established CAR-Ts duke it out over what could be a sizable slice of patients and sales, a growing menagerie of biotechs and pharmas looking for breakthroughs in next-gen cell therapy for cancer are also loudly shopping their wares this weekend.
This list runs long and includes some drugmakers that have recently made waves. The field has shown some early efficacy promise, but concerns over durability and a couple surprises in the clinic have churned out mixed results, so far. Take Allogene, for instance.
One of the premier names in crafting allogeneic — or “off-the-shelf” — cell therapies derived from donor cells rather than a patient’s own, Allogene was recently hit with a clinical hold for its ALLO-501 program after some patients reported chromosomal abnormalities. The company has an update on those Phase I trials Monday so at least we’ll know whether they were on the right track.
Meanwhile, you have a company like Fate, which is reading out data on its CAR-NK program FT596 — effectively strapping a CAR onto natural-killer cells derived from donor stem cells. Earlier this year, Fate turned out data questioning the durability of that drug despite some promising efficacy numbers.
All of these stories are part of a greater push into the future of cell therapy — particularly drugs that leverage the innate immune system. It will be interesting to watch how that develops.
New answers in hemophilia
An abstract to watch closely on Tuesday is Sanofi’s update on fitusiran, an siRNA therapy that silences the SERPINC1 gene leading to hemophilia A/B, could prove a game changer in treating that hematological disease.
Early data in the Phase III setting from this program showed a whopping 90% reduction in annualize bleeding rate, which would likely prove to be best-in-class efficacy if it holds up. Meanwhile, the safety profile for the drug has shown some hurdles, particularly on the clotting front.
Meanwhile, there are a range of potential gene therapies in the works for this program. Just this week, uniQure read out pivotal data for its gene therapy entranacogene dezaparvovec hitting its primary non-inferiority endpoint in annualized bleeding rate (ABR) after 18 months compared to baseline Factor IX prophylactic therapy. Factor IX is a protein that’s naturally produced in the body to help form blood clots and stop bleeding, and common treatments today are designed to replace the protein to achieve adequate clotting.
It’s worth noting that ASH isn’t just a blood cancer conference but a hematology conference as well, and this race will prove one to watch.
CD19/20 still dominates blood cancer drug development, but new targets are catching eyeballs
Another big late-breaking abstract on Tuesday is an update on Roche’s Polivy, an antibody-drug conjugate targeting the CD79b protein.
Polivy is one of a rare group of blood cancer meds approved to target anything but CD19 or CD20, two of the most highly validated targets in cancer care that have been the backbone for a range of approvals for decades. Roche, with a history driving three of the industry’s most successful cancer drugs in Avastin, Herceptin and Rituxan, knows that CD19/20 will play a big role in the future but is also willing to dabble in some interesting experiments.
One to watch is an update from Roche on combinations of Polivy with its investigational CD20xCD3 bispecific antibodies mosunetuzumab and glofitimab. There are lots of competing bispecifics working off those targets, and Roche is getting aggressive in pursuing combinations to get ahead.