A Q&A with Kantar’s Stephanie Hawthorne, Vice President of Oncology and Specialty Therapeutics
Oncology is one of the most exciting areas in healthcare today, as novel therapies continue to emerge that move forward our molecular understanding of the disease and offer effective treatment advances. In 2019, there were a variety of key developments and trends that emerged, as well as several important clinical trials that Kantar believes are critical to patients and the industry.
1. What therapeutic areas are “hot” for potential new, exciting treatments?
In pancreatic cancer, AstraZeneca and Merck & Co reported new data for Lynparza (olaparib) that provides new hope for a small subset of patients with pancreatic cancer. The data from the POLO trial demonstrated that Lynparza improved outcomes for pancreatic cancer patients whose disease has a BRCA mutation when used as maintenance therapy following response to initial chemotherapy. The benefit offered by Lynparza has been highly debated since it produced a 3.6-month progression-free survival (PFS) benefit but without impact on overall survival (OS); indeed, the FDA’s ODAC committee was also uncertain about the importance of its efficacy, issuing a 7-to-5 split decision in favor of approval, leading to FDA approval in December 2019. Lynparza’s approval now represents the first time a biomarker-selected targeted therapy has been approved in pancreatic cancer and also establishes maintenance therapy as a new treatment setting in this disease. Despite the moderate benefit offered by Lynparza in this setting, it offers a benefit nonetheless. This is especially appreciated in this disease, which is notoriously difficult to treat (three other agents failed in their pivotal trial efforts in this disease this year alone), and where a pressing need exists for more efficacious treatment options.
Astellas and Seattle Genetics have earned FDA approval for Padcev (enfortumab vedotin) for treatment of metastatic urothelial cancer (mUC) patients who have failed prior platinum and a PD-(L)1 inhibitor. Seattle Genetics has been making its name with antibody-drug conjugates (ADCs), and Padcev is the latest to impress. Approval was based on impressive data from a mid-stage trial; in the EV-201 trial, Padcev produced a 44% overall response rate with a duration of response of 7.6 months. The rationale behind ADCs is to use an antibody to target cancerous cells, delivering a toxic payload that destroys tumor cells but has minimal effect on healthy cells. Not only is Padcev an exciting new option because of the limited treatment options available for relapsed/refractory mUC, but also, in-part, because it’s the first therapy to be approved in a post-checkpoint inhibitor setting – something that’s increasingly being recognized as a new niche indication given the expansive presence of checkpoint inhibitors nowadays.
In breast cancer, there has been a plethora of exciting activities. In the HER2+ space, the field is now poised to have 2-3 new entrants in the post-trastuzumab metastatic setting. Daiichi Sankyo and AstraZeneca’s antibody drug conjugate Enhertu (trastuzumab deruxtecan) received FDA accelerated approval in third-line or later mBC based on a single-arm Phase 2 trial that produced a 60 percent response rate and 22-month PFS. Seattle Genetics’s tucatinib reported a 34 percent improvement in PFS and a 4.5-month OS benefit when combined with trastuzumab and capecitabine; tucatinib has now been filed for approval with the FDA and EMA, with approval expected in mid- and late-2020, respectively. Other agents also seeking approval in this same setting are MacroGenics’s margetuximab and Puma’s Nerlynx. Certainly the competition will be fierce in this setting! Meanwhile, in HR+/HER2- breast cancer, the biggest news of the year has been the OS benefits that were demonstrated after long-term follow-up of several pivotal trials for Novartis’s Kisqali (ribociclib) and Lilly’s Verzenio (abemaciclib). These are the first times CDK inhibitors have demonstrated survival benefits in this setting, and with both of these drugs being able to promote to their OS benefit they will provide a stiff challenge to Pfizer’s incumbent, Ibrance (palbociclib), which is unable to make such a claim.
It’s always exciting to observe novel therapeutics demonstrate exquisitely strong clinical benefits in molecularly targeted patient types. That has been a trend over the years and one that continues to excite. Right now, RET+ cancers are hot, with Eli Lilly’s selpercatinib seeking approval (with priority review) in RET+ NSCLC and thyroid cancers and Blueprint Medicine’s pralsetinib seeking approval in RET+ NSCLC. Blueprint Medicine also gained the first ever approval in PDGFRA mutant GIST with Ayvakit (avapritinib). And, of course, who can forget the tumor agnostic approvals of Roche’s Rozlytrek and Loxo/Lilly’s Vitrakvi for NTRK+ solid tumors. These are just a handful of the recent approvals in novel biomarker-selected indications in oncology. And while these indications usually represent a small number of eligible patients, the drugs tend to produce very high response rates with long durations of response due to their impact on molecular markers that are driving the tumor’s proliferation and/or survival. This is what makes these drugs so exciting for patients and pharma.
2. What are some of the most notable molecules in early-stage clinical development?
It’s not just the big late-stage trials showing promise. Molecules at the early stage of clinical development are also generating strong interest. One such example is KRAS inhibitors in NSCLC and other solid tumors. Amgen made a splash at AACR and ASCO 2019 with the promising activity of AMG-510, and similar excitement was generated at ESMO 2019 for Mirati Therapeutics’s MRTX849. Scientists have known for years about the role mutant KRAS can play in cancer but have never been able to make a drug that interacts with the dysfunctional protein. These drugs have captured the imagination of many oncologists because they work in a completely new way, by covalently bonding to the mutant protein and holding it in the inactive form. AMG-510 and MRTX849 have both showed promise in advanced solid tumors with the mutation known as KRASG12C, found in around 13 percent of lung adenocarcinomas and 1-3 percent of other solid tumors. While the last few years have been dominated by the rise of immunotherapies, there still remain many other promising mechanisms of action in development.
3. What are some of the new drug molecules in late-stage studies with blockbuster sales potential?
Daiichi Sankyo and AstraZeneca’s antibody drug conjugate Enhertu (trastuzumab deruxtecan), discussed above, is one such potential blockbuster. In March 2019, AstraZeneca entered into a nearly $7 billion commercialization and development agreement with Daiichi Sankyo regarding Enhertu, which looks on-track to payoff after the drug registered $29 million in revenue during its first week of sales (based on approval December 23, 2019, and Daiichi-reported sales for their fiscal Q3 2019 (Oct-Dec 2019), reported January 31, 2020). Analysts also predict that Immunomedics’ sacituzumab govitecan could reach blockbuster status based on its pivotal development in triple-negative breast cancer and metastatic bladder cancer. Meanwhile, Janssen’s FGFR inhibitor Balversa (erdafitinib) and BeiGene/GSK’s BTK inhibitor Brukinsa (zanubrutinib) also have blockbuster potential, stemming initially from their 2019 approvals in FGFR mutant bladder cancer and mantle cell lymphoma, respectively, as well as potential future approvals in other indications.
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