(A) (D)ouble (C)onquest
Antibody-drug conjugates (ADCs) got the week started off with a bang on Monday morning when Roche and partners AstraZeneca and Daiichi Sankyo revealed successful pivotal readouts for their respective Polivy (polatuzumab vedotin) and Enhertu (trastuzumab deruxtecan) that should pave their way much earlier in treatment paradigms. (See ViewPoints: An ADC hat-trick.)
Polivy hit its primary endpoint of progression-free survival (PFS) in the Phase III POLARIX trial in front-line diffuse large B-cell lymphoma (DLBCL), making it the first therapy to beat the standard of care in almost two decades. That said, a key opinion leader who spoke with FirstWord this week said the CD79b-targeting ADC is not yet a shoo-in to dominate the space. More analysis here.
In addition, AstraZeneca’s big bet on Enhertu looks a lot closer to coming good after the Daiichi Sankyo-discovered product hit significance on PFS – also the primary endpoint – in the Phase III DESTINY-Breast03 study in second-line HER2-positive breast cancer. Stay tuned as FirstWord will be speaking to a leading oncologist about these findings early next week.
Seagen looks elsewhere
Staying in the ADC realm, Seagen coughed up $200 million to license ex-Asian rights to disitamab vedotin (also known as RC48) from China-based RemeGen. The HER2-targeting ADC is conditionally approved in the originator’s home country and ready to begin a Phase II trial in the US to treat metastatic urothelial cancer, for which it has breakthrough designation from the FDA.
The move was interesting not just because it was the latest example of a Western biopharma looking to the Far East for innovation, but the fact it was Seagen – one of the early leaders in ADC development – made all the more intriguing.
FDA zigs again
Investors hate uncertainty so this week’s news that the FDA had thrown an unexpected monkey wrench in Axsome Therapeutics’ operations undoubtedly raised some hackles, especially coming just days before the company’s PDUFA date for major depressive disorder (MDD) candidate AXS-05 set for August 22.
What exactly the problem is remains to be seen as Axsome was only able to disclose that it had received a letter from the agency citing “deficiencies” with the application for AXS-05 that precluded discussions about labeling and post-marketing commitments.
Dicerna’s PH plans look dicey
Nedosiran hit the mark in a Phase III trial to treat primary hyperoxaluria (PH) but Dicerna shares were punished after a closer look at the top-line results showed the small interfering RNA (siRNA) candidate only worked in type 1 (PH1) patients with almost no signs of activity in type 2 (PH2).
This is shaping up to be a commercial problem because Dicerna will be coming to market well after Alnylam Pharmaceuticals’ Oxlumo (lumasiran), which is only approved in PH1. The big selling point for nedosiran was thus expected to be its broader utility, and without that Dicerna will be forced to lean on more modest advantages such as more convenient dosing. More here.
Boost for COVID-19 vaccines
Late on Thursday night the FDA put to rest the ‘will it or won’t it?’ question by approving a third booster dose of COVID-19 vaccines from Pfizer/BioNTech and Moderna for use specifically in individuals with weakened immune systems.
The decision may have arrived a little sooner than expected as the US Centers for Disease Control and Prevention (CDC) is set to meet on August 13 to issue recommendations about administering booster shots this same population.
It is a boon for the aforementioned mRNA vaccine developers, who just reported eye-watering sales for the products in respective 2Q21 earnings, and this week’s approval will only accentuate this trend. Not everyone is ecstatic about the FDA’s decision, however, as the World Health Organisation (WHO) has been outspoken in its criticism of richer nations pushing for booster shots when so many people haven’t been given an initial dose throughout the developing world.
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