NEW YORK – Novartis reported on Wednesday that its oncology business unit comprised more than half of its pharmaceutical product sales in the fourth quarter and full year in 2021, and the Swiss drugmaker expects the momentum to continue in this segment on the strength of several highly anticipated precision oncology programs, including a new radioligand therapy for metastatic prostate cancer.
The firm reported $13.23 billion in total revenues during the fourth quarter of 2021, including $6.8 billion in pharmaceutical sales, of which oncology drugs contributed $3.9 billion. For the full year, Novartis' total revenues were $51.63 billion, of which oncology drugs contributed $15.5 billion of the $26.5 billion netted by therapies. In 2020, the company recorded oncology drug sales of $3.8 billion in the fourth quarter and $14.7 billion during the full year.
In an earnings call, Novartis executives highlighted the strong performance in 2021 of the CDK4/6 inhibitor Kisqali (ribociclib) and the BRAF- and MEK-inhibiting agents Tafinlar (dabrafenib) and Mekinist (trametinib). Kisqali sales grew 36 percent to $937 million in 2021, while the Tafinlar-Mekinist combination grew 10 percent year over year to $1.69 billion. Meanwhile, the firm's autologous CD19-directed CAR T-cell therapy Kymriah (tisagenlecleucel), a relatively newer product marketed for relapsed or refractory diffuse large B-cell lymphoma and acute lymphoblastic lymphoma, also showed promising growth from 2020 to 2021, increasing 24 percent to $587 million.
The firm is eager to expand these products into new indications and grow their market share and revenues accordingly. For Kisqali, for instance, the firm recently initiated the Phase III HARMONIA trial to evaluate the agent against palbociclib (Pfizer's Ibrance) and is anticipating a readout from the Phase III NATALEE trial evaluating the agent in the adjuvant treatment setting by the end of this year.
For Tafinlar and Mekinist, Novartis expects future growth for the combination to come from the adjuvant melanoma and non-small cell lung cancer settings, as well as from increased uptake in China, Susanne Schaffert, head of Novartis' oncology business unit, said during the call.
In addition to growing the market for its existing products, Novartis is also advancing new programs that it believes could herald in a "paradigm shift" for large patient populations with an unmet need. Perhaps the most highly anticipated of these programs is the potential launch this year of the radioligand therapy 177Lu-PSMA-617 for metastatic castration-resistant prostate cancer.
Novartis and other experts in the field are optimistic that the US Food and Drug Administration will approve this treatment — most likely later this quarter — based on positive results from the Phase III VISION trial. That study showed an overall survival benefit with the targeted radioligand versus standard of care in prostate-specific membrane-antigen (PSMA)-positive mCRPC patients. Given the buzz around this product, Novartis is already gearing up for commercial launch.
As a starting point, the firm is planning to launch the therapy in roughly 225 treatment centers in the US and 200 centers in the EU. "We don't foresee any hospital capacity constraints for the launch in this … population," said Schaffert.
Still, some in the field have worried that if the radioligand therapy is approved, not all patients who could potentially benefit from it will be able to access it. The "unsealed" radiation therapy will require quite a bit of physical space to avoid contamination at treatment centers, as well as investment into special equipment and expertise. All this means that many patients will likely have to travel to major cancer centers to receive the therapy, and some could also face insurance barriers.
Even though Novartis has yet to bag its first approval for 177Lu-PSMA-617, the firm is already planning how to expand the therapy's patient population. Phase III trials are ongoing to move the treatment into other indications, including in prostate cancer patients who are hormone-sensitive as well as those not previously treated with taxane-based chemotherapy. These additional indications could quadruple the eligible patient population for 177Lu-PSMA-617, Schaffert said.
"In this [previously treated, mCRPC] patient population, there is basically no alternative, and 177Lu-PSMA-617 has demonstrated superiority versus the standard of care, so we expect there to be quite a big interest," she said. "We already see quite a high demand."
Beyond the radioligand space, Novartis is revamping its cell therapy program with a new platform for developing autologous therapies, dubbed T-Charge. While the data are still very early, the goal of T-Charge is to limit the amount that a cell therapy needs to be expanded ex vivo, which can exhaust cells. Instead, the idea is to produce the cells such that they expand once they're infused inside the body.
Other cell therapy-focused biotech firms have been trying variations of this in vivo expansion approach as well, in part because T-cell exhaustion is one of the main limitations seen with first-generation CAR T-cell therapies like Novartis' Kymriah. "What's unique about this platform is its ability to preserve T-cell stemness, [or] the ability of T cells to regenerate themselves and hopefully lead to more long and durable responses," Novartis CEO Vas Narasimhan said during the call, adding that it should also shorten the turnaround time for harvesting, modifying, and reinfusing patients' immune cells.
Novartis is using T-Charge to develop an autologous CD19-directed CAR T-cell therapy for certain lymphoma and leukemia patients, dubbed YTB323, and a BCMA-directed version for multiple myeloma patients, called PHE885. Both of those therapies are in Phase I trials, but response rates have been encouraging. For example, Novartis has reported a 73 percent complete response rate for 15 YTB323-treated DLBCL patients and a 100 percent overall response rates in six PHE885-treated multiple myeloma patients.
Narasimhan shared that Novartis plans to report out six-month data from these early trials over the coming months and begin a Phase III trial this summer for the DLBCL therapy. In time, the firm wants to bring additional targets onto the T-Charge platform, too.
Finally, following the FDA approval of its STAMP inhibitor Scemblix (asciminib) in October 2021, Novartis is enthusiastic about the treatment's launch in chronic myeloid leukemia patients, including those previously treated with at least two tyrosine kinase inhibitors and those with Philadelphia chromosome-positive cancers harboring a T315I mutation. The drugmaker is now evaluating the drug in the first-line CML setting and eyeing regulatory filing for 2025.