2-94 (University of South Australia)

By 2030, Pfizer expects about two-thirds of its oncology revenue will be coming from new molecular entities and new indications from existing products. In what CEO Albert Bourla, Ph.D., called an update to a top priority at Pfizer, the company on Thursday systemically laid out its new oncology strategy following the $43 billion acquisition of antibody-drug conjugate specialist Seagen. The company aims to have at least eight blockbuster cancer drugs by 2030, Pfizer’s newly minted chief oncology officer, Chris Boshoff, Ph.D., said during an investor event Thursday as he unveiled the strategic priorities. By then, Pfizer hopes to double the number of patients treated with its innovative cancer medicines from about 2.3 million in 2023. The new plan also sees Pfizer focusing on four main cancer types—breast cancer, genitourinary cancer, blood cancer and thoracic cancers—all of which the company already has commercial products in. “Within these areas, we’re initiating parallel earlier-line trials where the addressable population is the greatest, aiming to both accelerate a new wave of breakthroughs and move approved medicines into earlier lines of treatment,” Boshoff said. Pfizer bought Seagen and devised a new oncology blueprint as top-selling cancer drug Ibrance declines, and as its collaboration revenue from Astellas-partnered Xtandi runs flat. Both drugs are expected to lose market exclusivity in 2027. And the addition of Seagen brings Pfizer to what Boshoff called an inflection point in its position in the oncology field. Pfizer on Thursday stopped short of providing a specific sales projection for the oncology franchise by 2030. The company anticipates “continued strong sales and profit growth in oncology through the end of this decade,” oncology commercial chief Suneet Varma said. By then, about two-thirds of the risk-adjusted oncology revenue will be coming from new molecular entities and new indications from existing products, he added. Before the Seagen deal, Pfizer’s top three cancer drugs—Ibrance, Xtandi and Inlyta—were all small molecules. Now, the New York pharma aims to increase the proportion of biologics in its revenue mix from 6% to 65% by 2030. Touting Pfizer’s ability to boost the former Seagen portfolio, Boshoff pointed to Pfizer’s 10 manufacturing sites that are churning out oncology drugs on three continents, versus one for Seagen, plus six times the capacity for vial volume for antibody-drug conjugate (ADC) production than Seagen alone. Pfizer has commercial presence in over 100 countries, and the combined customer-facing commercial team is triple the size of Seagen’s own, he noted. In breast cancer, Seagen brings over HER2-targeted ADC disitamab vedotin and the tyrosine kinase inhibitor Tukysa. And to carry on Ibrance’s legacy, Pfizer is working on a CDK4 inhibitor called aitrmociclib, which is already in phase 3 development in second-line HR-positive, HER2-negative breast cancer, with a first-line trial planned to start in the second half of this year. Despite growth potential from the new drugs, the Ibrance patent cliff will be so steep that Pfizer expects breast cancer’s contribution to total oncology sales will drop to about 10% by 2030 from about 40% in 2023, Varma told investors during Thursday’s event.  Instead, genitourinary cancer is expected to become Pfizer’s largest oncology franchise, with about 35% contribution. In this area, the combination of Pfizer’s Astellas-partnered Padcev and Merck’s Keytruda is becoming a new standard of care in front-line bladder cancer. And disitamab vedotin, which is already sold in China by RemeGen, is also being tested alongside Keytruda in a phase 3 trial in previously untreated, HER2-expressing bladder cancer. What’s more, Pfizer is also counting on a longer follow-up of overall survival data from the phase 3 TALAPRO-2 trial later this year to potentially expand the combination of its PARP inhibitor Talzenna and Xtandi to a broader prostate cancer population. Besides, the company is looking to launch two phase 3 trials this year in metastatic castration-resistant prostate cancer for mevrometostat. Pfizer recently started a push into blood cancers with the FDA’s approval for Elrexfio, a BCMA-targeted bispecific drug. Again, multiple phase 3 trials are ongoing for the multiple myeloma therapy, including two trials in newly diagnosed patients either as a post-transplant maintenance treatment or for transplant-ineligible patients. Plus, Seagen comes with Adcetris, an established blockbuster for classical Hodgkin lymphoma. As for thoracic cancer, Pfizer has a relatively small presence there today. In lung cancer, Pfizer is working to establish its third-generation ALK inhibitor Lorbrena as the new standard of care in the field. The integrin beta-6-directed ADC sigvotatug vedotin recently entered phase 3 testing in pretreated nonsquamous non-small cell lung cancer, and a readout is expected around 2026 or 2027. In 2023, Pfizer’s oncology sales dropped 3% at constant exchange rates to $11.6 billion, despite a small contribution from the Seagen products in the last few days of 2023. Declines from Ibrance and Xtandi collaboration revenue drove the overall decrease.

The annual San Antonio Breast Cancer meeting drew clinicians and researchers for a few days at the end of 2023 to discuss advances in the field. While the past several decades have seen progress in early detection, recent innovations in metastatic breast cancer—or cancer that has spread to distant parts of the body, including the bone, brain, or lungs—continues to cause excitement. In the US, around 40,000 women and 4,000 men are diagnosed annually with metastatic breast cancer, and around 200,000 Americans are living with advanced disease. But nearly 300,000 US citizens are diagnosed with breast cancer annually, and the specter of this non-metastatic disease converting to metastatic disease amplifies the weight of this issue. Two thirds of all breast cancer patients have a type of breast cancer called hormone receptor-positive (HR+). For these patients, a key part of treatment has been reducing the activity of hormones like estrogen, which fuel the growth of cancer cells. In 2017, the standard treatment approach changed to include the use of one of three drugs called CDK4/6 inhibitors – abemaciclib (brand name: Verzenio), ribociclib (brand name: Kisqali), or palbociclib (brand name: Ibrance). These drugs are used alongside other medications that modify hormone levels, such as letrozole or fulvestrant. These drugs have improved both PFS (progression free survival or the time until disease starts to grow again) as well as the overall survival of patients, although that is much more modest and the 5 year survival rate for this class hovers around 30%. Unfortunately, many patients appear to be intrinsically resistant to these therapies and gain no benefit at all, and most others acquire resistance with time, forcing the field to reckon what is next in the post CDK4/6 inhibitor space? While there have been advances in developing drugs that can adjust hormone levels, they haven’t led to significant improvements in how long people live with the disease. As a result, there’s still a need for new therapies that can make a bigger difference in improving survival rates. But the field is responding and several new medicines have entered clinical usage in the last few years, with the goal of providing additional choices to delay the use of chemotherapy and increase overall survival. The consensus now is that these CDK4/6 inhibitor resistant breast cancer patients should be screened for several genetic perturbations, which are now actionable in terms of novel therapies. Olaparib, capivasertib or everolimus are all new additions to the post CDK4/6 inhibitor arsenal. This use of precision oncology screening in the breast cancer space reinforces the observation that not all metastatic disease is the same and this heterogeneity requires understanding on a per-patient level and therapies may have to be administered sequentially as disease evolves. Even when a patient needs to move to chemotherapy, for many, a less toxic option may now be available. Enhertu is an antibody drug conjugate (ADC), or a chemotherapy linked to an antibody that recognizes the Her2 receptor. This therapy was approved with great fanfare as it helps target the chemotherapy to the Her2+ tumor cell and has been shown to reduce toxicity relative to the untethered chemotherapy. Many CDK4/6 inhibitor resistant patients have now been reclassified as eligible for this therapy with the advent of a new biomarker designation, Her2 low. Of course, all of these new therapies carry potential adverse effects with them, and that is part of the reason for the robust pipeline of new therapies in the phase one clinical trial or preclinical setting. The clinical resistance seen with the CDK4/6 inhibitors appears to be due at least in part to the activation of a previously undrugged target, CDK2. While the field has tried unsuccessfully for several decades to drug CDK2, new more specific CDK2 monotherapies have entered phase one (Ph1a) trials over the last year (Pfizer, Blueprint Medicine, Incyclix, Incyte). The CDK2 monotherapies may have more limited response due to observations that both CDK4/6 and CDK2 have to be inhibited simultaneously, so there is effort to combine them with either existing CDK4/6 inhibitors such as Ibrance or new, more untested CDK4 inhibitors: Pfizer is testing a new CDK2 and CDK4 inhibitor combination and Beigene will begin testing of their new monotherapy combinations. The incredible focus in the drug-resistant breast cancer space will likely drive the development of therapies that will ultimately cross over into usage in other tumor types. For example, the Destiny trial last year demonstrated that Enhertu, which was originally developed for and approved in a different form of breast cancer, Her+ BC, showed response in numerous other tumor types, including uterus, cervix, ovaries, bladder, which were Her2+ paving a way for its broader use. A second observation is the sequencing of these new therapies combined with biomarker analysis, or identifying additional actionable targets in each patient, will be important to continually add to the therapeutic pipeline for patients. Creating a repertoire of add-on possibilities should help reduce the stigma of metastatic breast cancer as a terminal disease. Public domain image by the National Cancer Institute