Pressure on Abbvie's pipeline grows

Abbvie will need more than Skyrizi and upadacitinib to fill a Humira-shaped hole, and there are a few early-stage candidates it reckons could fit the bill.

Abbvie’s first quarter was surprisingly healthy, with sales of Humira holding up in the face of biosimilar competition.

But Humira erosion is set to worsen next quarter, and Abbvie will need new products to pick up the slack. In the near term investors will  track launches of the newly approved psoriasis therapy Skyrizi and the rheumatoid arthritis contender upadacitinib; in the longer term the group’s early-stage pipeline will also have to deliver. 

On yesterday’s earnings call, Abbvie execs highlighted several projects that could have promise. Some of them, however, look like long shots.

Abbvie's pipeline highlights
Project Description Indication Status Trial ID
Depatuxizumab mafodotin Anti-EGFR ADC Glioblastoma  Phase II/III  NCT02573324
Navitoclax/ABT-263 Bcl-2 & Bcl-XL inhibitor Myelofibrosis Phase II  NCT03222609
ABBV-323 Anti-CD40 MAb Ulcerative colitis Phase II NCT03695185
ABBV-599 Jak1/BTK combo Rheumatoid arthritis Phase II NCT03682705
ABBV-8E12 Anti-tau MAb Alzheimer's, progressive supranuclear palsy Phase II NCT02880956, NCT02985879
ABBV-621/APG880* Trail agonist Solid tumours Phase I NCT03082209
ABBV-151/ARGX-115** Anti-Garp MAb Solid tumours Phase I +/- ABBV-181 (anti-PD-1) NCT03821935
ABBV-3373 Anti-TNF steroid ADC Rheumatoid arthritis Phase I  NCT03823391
AL002*** Trem2 inhibitor Alzheimer's  Phase I NCT03635047
AL003*** Anti-CD33 MAb Alzheimer's  Phase I NCT03822208
*Licensed from Apogenix; **Licensed from Argenx; ***Developing in partnership with Alector
Source: Company website, EvaluatePharma.

The most advanced, and one of the more precarious, is depatuxizumab mafodotin, which is in a phase II/III trial in patients with first-line glioblastoma and due to complete next year.

Abbvie’s president, Mike Severino, said this project did not get a lot of attention, but there could be a reason for that: glioblastoma is notoriously difficult to treat, so hopes for the asset are presumably low.

Abbvie has also put several bets on another tricky area, Alzheimer’s disease, with an anti-Tau antibody, ABBV-8E12, plus two earlier-stage projects being developed in partnership with Alector. Still, at least these are not targeting beta-amyloid, a strategy that should have been killed off by the failure of Biogen’s aducanumab. Biogen, too, is increasingly looking at Tau.

Meanwhile, navitoclax and ABBV-599 merely look like extensions of existing franchises, with the former a Venclexta follow-on and the latter a combination of upadacitinib and the BTK inhibitor ABBV-105.

Mind the Garp

The most interesting asset on this list is probably the anti-Garp antibody ABBV-151, which is now known to be the Argenx-originated compound ARGX-115. The project recently went into a phase I trial testing it alone or in combination with Abbvie’s PD-1 inhibitor ABBV-181 in solid tumours.

ABBV-151 is thought to work by inactivating TGF-β and T regulatory cells, thus reversing the immune system suppression seen in cancer. This is a hot area, with plenty of other companies also attempting to inhibit TGF-β (Scholar thinks Glaxo made a wise move to back Merck, March 13, 2019).

Even if this approach works and Abbvie can fight off competition, it will be some time before the company can reap the rewards. In the meantime, it is bullish about the chances of its new product Skyrizi, forecasting 2019 sales of $150m, with most of these coming in the second half. This is well above EvaluatePharma’s sellside consensus of $63m for this year.

Another recent launch, that of the endometriosis pain therapy Orilissa, has been slow, although Abbvie’s chief executive, Rick Gonzalez, said this was to be expected as the company has had to build the market. Despite the sluggish start, Abbvie is maintaining its guidance for 2019 Orilissa sales of $200m.

Hopes are also high for the Jak inhibitor upadacitinib, which is due an approval decision in rheumatoid arthritis in the third quarter. This is expected to get the go-ahead, but investors will want to see it avoid the black box warning over toxicity that has scuppered some other Jaks.

Perhaps tellingly, Abbvie is only seeking approval for a lower 15mg dose of upadacitinib, and with Galapagos’s filgotinib – which looks like a safer Jak – waiting in the wings, there are reasons to be cautious about the former’s chances.

Mr Gonzalez yesterday brushed off questions about potential acquisitions, saying only that Abbvie would consider deals for the right assets. 

With Humira biosimilars set to enter the US in 2023 the importance of the group’s new products and pipeline will only increase. Any slip-ups could lead to louder calls for a big buy, something Abbvie would no doubt prefer to avoid, as desperate buyers often make bad decisions.

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