CD1A

Pfizer thinned its sickle cell pipeline 10 months after its buyout of Global Blood Therapeutics. Pfizer is ringing the changes as it exits the second quarter, tossing out a midstage pneumococcal vaccine candidate and a handful of phase 1 assets including a respiratory syncytial virus (RSV) prospect it picked up in last year’s ReViral takeover.  The quarterly pipeline update (PDF) features the removal of two phase 2 assets, including the previously disclosed defenestration of its oral obesity and diabetes candidate lotiglipron over safety concerns. The other phase 2 candidate to get the ax in the update is PF-06842433, a vaccine that was in development for the prevention of invasive and noninvasive pneumococcal infections in infants and children. Pfizer ran (PDF) a phase 1/2 clinical trial of the seven-valent pneumococcal conjugate vaccine from 2018 to 2020. The vaccine candidate was designed to complement the pneumococcal coverage provided by Prevnar 13, but, with Prevnar 20 now approved, Pfizer has moved on from the program. The update also covers the discontinuation of six phase 1 assets, including PF-07923567. The N-protein inhibitor, also known as RV-299, is one of the RSV candidates that Pfizer added to its pipeline in a deal to buy ReViral for $436 million upfront last year. Work on the most advanced program included in the deal, sisunatovir, continues, but Pfizer has decided it can do without PF-07923567. Pfizer is also jettisoning a pair of atopic dermatitis programs and another pair of solid tumor assets. In atopic dermatitis, the Big Pharma followed up the discontinuation of one topical “soft” JAK inhibitor last year by axing a similar molecule that it was studying in the same phase 1 trial. Alongside that, it has cut PF-07242813, a CD1a inhibitor, after wrapping up a phase 1 trial in healthy volunteers and atopic dermatitis patients. The solid tumor discontinuations fall on the AXL/MERTK inhibitor PF-07265807 and the IL15 activator PF-07209960. Pfizer acquired the AXL/MERTK inhibitor in the Array BioPharma buyout, but evidence the mechanism lowers the immune activation threshold and boosts anti-tumor immunity has failed to yield a clinical candidate the drugmaker thinks warrants further development. Finally, Pfizer has thinned its sickle cell pipeline 10 months after its buyout of Global Blood Therapeutics positioned it as a force in the indication. The discontinuation affects PF-07209326, an anti-E-selectin inhibitor that was in development at Pfizer prior to the Global Blood takeover. The confirmation follows the news last week that Pfizer is walking away from a sickle cell disease licensing deal with Syros Pharmaceuticals that it inherited from its takeover of Global Blood.

Headline results for the second quarter: Revenue: $12.7 billion (forecasts of $13.3 billion), down 54% Profit: $2.3 billion, down 77%Note: All changes are versus the prior-year period unless otherwise statedWhat the company said:Chief financial officer David Denton remarked "the second quarter…delivered solid 5% operational revenue growth, excluding our COVID-19 products, and our year-to-date results are in line with our expectations." However, Denton said that despite expected accelerated growth of non-COVID products in the second half, the company may have to launch a cost-cutting programme if sales of Comirnaty and Paxlovid continue to underperform.According to Pfizer, it anticipates more clarity for COVID revenue in the second half on a likely rise in infections in the fall season and the US switching to a commercial market for the products from government contracts. "To that end, if our COVID-19 revenues are less than what we assumed, we are prepared to launch an enterprise-wide cost improvement programme," Denton explained.Meanwhile, CEO Albert Bourla noted that Pfizer continues "to make progress toward" closing the proposed $43-billion acquisition of Seagen later this year or in early 2024. The executive added that the drugmaker is working to fulfil requests for further information on the transaction from the US Federal Trade Commission.Other results: Primary care sales: $5.8 billion, down 72% Eliquis alliance revenue and direct sales: $1.8 billion, up 1% Comirnaty: $1.5 billion, down 83%, but ahead of forecasts of $1.4 billion Prevnar/Prevenar 13 & 20: $1.4 billion, down 3% Nurtec ODT/Vydura: $247 million Paxlovid: $143 million, down 98%, missing estimates of nearly $1.1 billion Specialty care sales: $3.7 billion, up 9% Vyndaqel/Vyndamax: $782 million, up 42% Xeljanz: $469 million, up 9% Enbrel (outside the US and Canada): $219 million, down 15% Sulperazon: $177 million, down 15% Oxbryta: $77 million Oncology product sales: $3 billion, down 4% Ibrance: $1.2 billion, down 6% Xtandi alliance revenue: $305 million, up 5% Inlyta: $262 million, down 4% Looking ahead:Pfizer now expects revenue for 2023 to be between $67 billion and $70 billion, with the top end lowered by $1 billion from prior guidance. The company reaffirmed that revenue from Comirnaty is seen reaching approximately $13.5 billion, down 64% from 2022, while Paxlovid sales are set to fall 58% to around $8 billion.Meanwhile, Pfizer reiterated that earnings per share for this year are still predicted to be between $3.25 and $3.45, which represents roughly a 50% drop from 2022.Commenting on the recent tornado damage to its manufacturing plant in Rocky Mount, North Carolina, the company said "there does not appear to be major damage to the production areas," with the majority of issues restricted to the warehouse facility. Pfizer indicated that it is working to move finished medicines – which include sterile injectables – to other nearby sites for storage, while it is also exploring alternative manufacturing locations.Pipeline updates:Pfizer disclosed a number of recently-discontinued programmes, led by the mid-stage vaccine PF-06842433 for invasive and non-invasive Pneumococcal infections in infants and children. The cull comprises six Phase I assets, including the topical soft JAK inhibitor PF-07295324 and the CD1a inhibitor PF-07242813, which were both under development for atopic dermatitis.Also on the chopping block were the AXL/MERTK inhibitor PF-07265807 and the IL-15 activator PF-07209960 in oncology, as well as the anti-E-selectin inhibitor PF-07209326 in sickle cell disease and the N-protein inhibitor PF-07923567/RV-299 for respiratory syncytial virus infection.