CAR-Ts May Be Closer Competitors To Lilly’s Jaypirca Than Fellow BTK Inhibitors
Executive Summary
The Loxo@Lilly drug got FDA accelerated approval in mantle cell lymphoma as the first non-covalent BTK inhibitor, enabling its use in post-BTKi disease.
Eli Lilly and Company's newly approved, Jaypirca (pirtobrutinib), may have the same target as BTK inhibitors already on the market, but it belongs to a different class in terms of how it will fit into the mantle cell lymphoma (MCL) treatment paradigm, and that is key to the company's commercial strategy around the drug.
Lilly's Loxo subsidiary announced 27 January that the US Food and Drug Administration granted accelerated approval of Jaypirca for patients with MCL who have received at least two prior therapies that include a BTK inhibitor. Jaypirca marks the first approval of a non-covalent BTK inhibitor, meaning that it can be used even after patients have developed resistance to approved covalent BTK inhibitors.
For the moment, the targeted population remains one that is underserved, but still very small. Lilly is also pursuing development of Jaypirca in a larger patient population, chronic lymphocytic leukemia (CLL).
“I think there’s a reasonably high degree of awareness of the medicine, sort of right out of the gate, which is great,” Loxo@Lilly CEO Jacob Van Naarden told Scrip. He said the population amounts to around 1,000 people in the US, “but it’s a rare population, and so commercially, I think our expectations are fairly measured here in the near term.”
Drug Won’t Compete Against Other BTKis Just Yet
The approval stemmed from results for a subset of patients from the Phase I/II BRUIN trial that included 120 patients who received Jaypirca until disease progression or unacceptable toxicity. The results showed an overall response rate (ORR) of 50%, including a complete response (CR) rate of 13%. The median duration of response (DoR) was 8.3 months, while the DoR rate at six months was 65.3%.
BRUIN also included cohorts in other non-Hodgkin lymphoma subtypes, including follicular lymphoma (FL), marginal zone lymphoma (MZL), diffuse large B-cell lymphoma (DLBCL), Waldenström’s macroglobulinemia (WM) and also chronic lymphocytic leukemia (CLL), which is another major area of development for Jaypirca apart from MCL.
Data presented to date, such as at the American Society of Hematology’s 2020 meeting, have shown the drug to be highly effective in patients who have received a covalent BTK inhibitor. (Also see "LOXO-305 Comes Out Swinging In Battle Of BTK Inhibitors" - Scrip, 5 Dec, 2020.) Covalent BTK inhibitors include AbbVie Inc./Johnson & Johnson’s Imbruvica (ibrutinib), AstraZeneca PLC’s Calquence (acalabrutinib) and BeiGene, Ltd.’s Brukinsa (zanubrutinib). Another non-covalent BTK inhibitor in development is Merck & Co., Inc.’s MRK-1026.
Jaypirca is in head-to-head studies against the covalent BTK inhibitors, but Van Naarden said it would be a long time before those read out. For the time being, it is not really in competition with those drugs despite having the same target, and if it beats out the other BTK inhibitors in those studies, the question of how to use it in relation to them would come down to sequencing by physicians.
“You can have the same target and still bind and act differently, so those three medicines are all covalent BTK inhibitors – they’re all competing with each other, sort of in the same turf battles of these various diseases,” he said. “Jaypirca is a non-covalent, or reversible BTK inhibitor, which isn’t just sort of a moniker – that’s the reason it works in patients who failed those drugs.”
In that sense, Jaypirca is competing more closely with chimeric antigen receptor T-cell (CAR-T) therapies, such as Gilead Sciences, Inc.’s Tecartus (brexucabtagene autoleucel), which are approved as later-line treatments. Although Loxo@Lilly didn’t price Jaypirca to compete against CAR-T, Van Naarden said its $21,000 per month wholesale acquisition cost (WAC) was also not based on the pricing of covalent BTK inhibitors and was instead based on what the company calculated as its value to the health care system.
The WAC is significantly higher than the list prices of its covalent counterparts, however. Morgan Stanley analyst Terence Flynn pointed out in a 27 January note that Imbruvica's WAC is $15,883 per month, while Calquence is $14,920 per months and Brukinsa is $14,487 per month, all before rebates and other discounts.
Van Naarden suggested Jaypirca might compete more directly with the other BTK inhibitors in the future, but it is a way off before the company thinks in those terms.
In the near-term, Jaypirca could serve as a bridge to CAR-T therapy, he added, which he said some physicians had brought up as a potential use case for the drug, particularly given some of the challenges around CAR-T despite its high degree of efficacy, such as patients unable to get CAR-T in time due to their disease being proliferative, along with financial issues or logistical issues getting into one of the cancer centers that offers it. However, that remains to be seen given that the company has not yet commercially launched the drug, which it plans to do in the coming weeks.
“I don’t know yet if that’s a use case that will emerge from the clinical community,” Van Naarden said. “But it’s possible.”
The Jaypirca approval in its initial small market population was an expected positive for Lilly, Morgan Stanley’s Flynn noted, pointing out that the larger market opportunity for the drug is in CLL, where Phase III trials are ongoing with results expected in the first quarter of 2024. “We model 2023 Jaypirca sales of $41m vs. consensus of $47m and project 2025/2030 unadjusted sales of $726bn/$3.5bn vs. consensus of $572mn/$2.5bn (unadjusted sales),” he said.