Buried deep in today’s fourth-quarter financials report from Sanofi is a slide detailing R&D pipeline changes, making it clear that the French group has been paying attention to recent trends in immuno-oncology, but also containing a few surprises.
Out go anti-Lag-3 and CTLA-4 approaches in oncology, and a pivotal combo study in first-line lung cancer has been canned, presumably as realisation dawned that competing against Keytruda was a non-starter. Among the surprises, an anti-BCMA bispecific enters phase I in multiple myeloma, just two days after Novartis and Gilead spelled out their reservations about competing in this crowded field.
On Tuesday Gilead took an extraordinary $820m charge to write off its anti-BCMA CAR KITE-585 in the face of fierce competition, while Novartis moved to strengthen its own asset, MTV273, by taking it forward in combination (Novartis and Gilead’s multiple myeloma CARs diverge, February 6, 2019).
Today Sanofi highlighted the recent start of recruitment into a phase I trial of REGN5458, a Regeneron-partnered anti-BCMA bispecific. This will have to contend with GSK2857916, an antibody-drug conjugate from Glaxosmithkline. Glaxo has vowed that ’7916 will be the first BCMA-targeting project to come to market.
If there is still space to compete in BCMA the same can apparently not be said about GIP/GLP1 mechanisms in diabetes. Lilly last year surged ahead in developing LY3298176, a novel GIP and GLP1 agonist, and Sanofi’s similarly acting offering, SAR438335, has been jettisoned from phase I.
In phase II discontinuations out goes SAR425899, a glucagon and GLP1 dual agonist for obesity and diabetes that had competed against Novo Nordisk’s NN9277. And, on the day that the Ablynx-derived Cablivi got US approval with a surprisingly benign label, Sanofi canned another Ablynx asset, the anti-RSV nanobody ALX0171.
There was good news this week for Sanofi when isatuximab scored a hit in the phase III Icaria-MM trial in multiple myeloma. While this anti-CD38 MAb faces the tall order of challenging Darzalex, Sanofi is moving forward with two phase II combo trials, one with Roche’s anti-PD-L1, Tecentriq, and the other with its own anti-PD-1 drug, Libtayo.
Lung cancer scrap
It is Libtayo, which posted sales of $15m in its first quarter on the market, that could attract most attention from investors today: Sanofi is scrapping its phase III trial in combination with Yervoy in first-line NSCLC patients expressing PD-L1 at 50% or above.
In this use Merck & Co’s Keytruda has a stranglehold, which will soon be broadened to include lower PD-L1 expressers. Similar PD-(L)1/CTLA-4 approaches from Astrazeneca and Bristol face a desperate battle for relevance (Bristol makes investors squirm a little more, January 24, 2019).
There is bad news for followers of Oxford Biomedica, whose myosin VIIA gene therapy UshStat Sanofi is discontinuing in phase II, and for Immutep, a major player in the Lag-3 mechanism. Sanofi’s Libtayo combination with REGN3767, an anti-Lag-3 MAb, is being scrapped in phase I; other anti-Lag-3s include Bristol’s relatlimab and Merck & Co’s MK-4280.
And, in addition to ending Libtayo’s Yervoy combination, the anti-PD-1 MAb’s combo with the in-house CTLA-4 inhibitor REGN4659 has bitten the dust, also in NSCLC. This will be taken as yet another vote of no-confidence in CTLA-4, and in the idea of trying to compete in lung cancer.
|Selected Q4 2018 pipeline changes for Sanofi|
|Isatuximab + Tecentriq||CD38 + PD-L1||Start of phase II in solid tumours||Darzalex, MOR202|
|Isatuximab + Libtayo||CD38 + PD-1||Start of phase II in lymphoma||Darzalex, MOR202|
|REGN5458||BCMA||Start of phase I in multiple myeloma||GSK2857916, MTV273, bb2121, JCARH125|
|BIVV003||Bcl 11A gene therapy||Start of phase I in sickle cell||Sangamo (partner)|
|SAR443060||RIP1 kinase||Start of phase I in ALS & Alzheimer's||GSK3145095 (oncology)|
|Libtayo + Yervoy||PD-1 + CTLA-4||Discontinuation of phase III in 1L NSCLC||Opdivo, Imfinzi, Bavencio|
|SAR425899||GLP1 + glucagon||Discontinuation of phase II in diabetes||NN9277|
|SAR438335||GLP1 + GIP||Discontinuation of phase I in diabetes||LY3298176, NN9423|
|SAR439794||TLR 4||Discontinuation of phase I in peanut allergy||Viaskin Peanut, AR101|
|REGN3767||Lag-3||Discontinuation of monotherapy & Libtayo combo||GSK2831781, IMP731, relatlimab, MK-4280|
|REGN4659||CTLA-4||Discontinuation of monotherapy & Libtayo combo||Yervoy, tremelimumab, AGEN1884, MK-1308|
|UshStat||Myosin VIIA gene therapy||Discontinuation of phase I in Usher syndrome 1b||Oxford Biomedica (former partner)|
|SAR228810||Protofibrillar amyloid-beta||Discontinuation of phase I in Alzheimer's||Gantenerumab, aducanumab, BAN2401|
|Source: company presentation.|