Pfizer applies COVID-19 vaccine lessons to boost evolving cancer pipeline

The speed with which Pfizer Inc. and German partner BioNTech SE developed and delivered their coronavirus vaccine has given the U.S. pharmaceutical giant a newly accelerated outlook on clinical trials in areas such as cancer, where Pfizer has an extensive pipeline.

The company has begun a mid-stage trial of its cancer treatment elranatamab in patients with multiple myeloma that, if successful, will ready the therapy for U.S. regulatory approval in June 2022. A number of practices used in the study were first applied in the race to be the first COVID-19 vaccine maker — when Pfizer was able to secure emergency authorization in the U.S. just eight months after signing the deal with BioNTech — Pfizer Oncology Chief Development Officer Chris Boshoff told S&P Global Market Intelligence in an interview.

"I think the COVID-19 vaccine delivery has changed the mindset of many, many colleagues within Pfizer and certainly our colleagues in clinical development of oncology," Boshoff said. "Internally, we are now applying learnings from this experience of accelerated development of elranatamab, and our ability to move at such extraordinary speed while maintaining focus on safety is really at the heart of what we want to do for this specific program."

Elranatamab is in a class of drugs called bispecific antibodies, which simultaneously bind to two different targets — Pfizer's version binds to B cell maturation agent, or BCMA, on the multiple myeloma cells and a CD3 receptor on cancer-fighting T cells. Several drugs in the same class from competitors including Regeneron Pharmaceuticals Inc., Johnson & Johnson, Amgen Inc. and Bristol Myers Squibb Co. are also in the works, so moving quickly through trials offers a competitive advantage.

Pfizer has incorporated more digital capabilities with virtual access to operations and data, Boshoff said. Trial site initiation, trial and safety data, side effect monitoring, blood tests and imaging have all been accessed through virtual systems in the elranatamab program.

"It is important to note that we are also doing certain things at risk to develop a commercial-ready product," Boshoff said. "Before, when we're in still in phase 1, that's not something we always did, especially for complex biologics, and now we are starting a very comprehensive program in parallel."

Two-pronged approach

The first indication for elranatamab that Pfizer is aiming for is in patients with multiple myeloma that has not responded to initial standards of care. In an early-stage study, the therapy was safe and showed an 83% clinical efficacy.

Elranatamab is also designed to be delivered to a patient underneath the skin, or subcutaneously, as opposed to a longer infusion.

"What we've learned is that subcutaneous delivery reduced the incidence and grade of cytokine release syndrome, which is a dose-limiting toxicity for any T cell-redirecting bispecific antibody," Boshoff said. "Subcutaneous dosing obviously has potential better safety, but can also be more convenient for patients and caregivers."

Pfizer has future plans for the molecule, as well, in what Boshoff calls a two-pronged approach to registrational trials for further indications as well as exploratory studies in combination with other drugs.

For multiple myeloma, Pfizer plans to bring elranatamab into earlier lines of therapy to treat a wider swath of patients. The company will announce a phase 3 study later in 2021, Boshoff said.

Pfizer is also moving ahead with elranatamab in combination with approved cancer medications like Revlimid and Pomalyst from Bristol Myers, as well as an investigational gamma secretase inhibitor from SpringWorks Therapeutics Inc.

"This is all to bring the medicine into the earlier line of therapy with potential with the right combination to truly cure some patients with multiple myeloma," Boshoff said.

Elranatamab will face competition from CAR-T cell therapies that have advanced to the market for many blood cancers, but Boshoff said the difficulties in manufacturing, cost of goods and global access for these cell therapies could allow biologics like bispecific antibodies to reach more patients.

"Apart from within highly specialized hematologic centers, in the short term we cannot see CAR-T cell therapies being a global accessible medicine like a subcutaneous-administered biologic," Boshoff said.

'The future is in combinations'

Oncology is a core franchise for Pfizer and the pharmaceutical giant has evolved to stay abreast of advances in the field, moving into more targeted therapies like elranatamab.

The company has 24 approved cancer medications, including small molecules, biologics, antibodies and biosimilars, and Boshoff said drug combinations are where the company is focusing its energy into the future.

Beyond blood cancers like multiple myeloma, the company's oncology outlook is spread across three distinct areas, Boshoff said — breast cancer; genitourinary cancers like bladder, renal and prostate; and colorectal cancer and melanoma, stemming from the 2019 acquisition of Array BioPharma.

These pillars stem from blockbuster drugs Bavencio, Xtandi and Ibrance, as well as newer drugs like Talzenna and the two treatments from Array called Braftovi and Mektovi.

Successful drug combinations for Pfizer in the past have included the dual therapy of Ibrance and endocrine treatment, which Boshoff said has more than just an additive effect on breast cancer. Braftovi and Eli Lilly and Co.'s Erbitux gained approval in colorectal cancer, while Inlyta and Merck & Co. Inc.'s Keytruda were approved for renal cell carcinoma.

"Our overall strategy is recognizing that we believe the future is in combinations," Boshoff said. "But it is very important for Pfizer and how we want to differentiate that we base our combinations on real, rational scientific insight or, even better, preclinical data that show a combination is more than additive."