Oncology Optimist

Pharmaceutical Executive, Pharmaceutical Executive-12-01-2021, Volume 41, Issue 12

After two decades at the forefront of hematology and oncology drug development, AbbVie’s vice president and global head of oncology clinical development, Mohamed Zaki, MD, PhD, is more hopeful than ever about recent advances in the space.

After finishing medical school in Egypt, Mohamed Zaki came to the United States where he gained a PhD at the University of Pennsylvania, before becoming an assistant professor. Moving into the pharmaceutical industry in 2001, he spent the next 17 years in increasingly senior roles in hematology and oncology, first at a small company, Centocor (a Johnson & Johnson subsidiary), then at Sanofi-Aventis, and later Celgene. In September 2018, after nine years at Celgene, he joined AbbVie as global head of hematology clinical development. In July of last year, he became AbbVie’s vice president and global head of oncology clinical development.

Zaki was attracted to AbbVie because of the “amazing science being done here in hematology and oncology,” which he has helped to advance since joining. He points to venetoclax and ibrutinib as “perhaps the best evidence” of this science. Venetoclax (branded as Venclexta) was initially developed as a targeted agent for the B-cell lymphoma-2 (BCL-2) protein. In 2016, it was approved by FDA for the treatment of chronic lymphocytic leukemia (CLL) in previously treated patients with the 17p deletion genetic mutation. It has since been approved for people with CLL or small lymphocytic lymphoma (SLL), with or without 17p deletion. In combination with azacitidine or decitabine, it also was approved in 2020 for the treatment of newly diagnosed acute myeloid leukemia (AML) in adults who are age 75 years or older.

“I used to treat patients with AML and it was almost a death sentence,” explains Zaki. “It was a horrible disease and nothing had been advanced for many years to treat those patients. The chemotherapy ended up killing them. Getting approval for a therapy that targets the disease, that can actually transform the patient’s life, was an extremely proud moment for me.”

Ibrutinib (branded Imbruvica) was originally approved by FDA in 2013 for the treatment of mantle cell lymphoma; the approval was expanded soon after to include CLL and SLL. In August 2018, ibrutinib in combination with rituximab was approved for the treatment of adults with Waldenström’s macroglobulinemia, a rare and incurable type of non-Hodgkin’s lymphoma.

Zaki also has great faith in navitoclax, AbbVie’s investigational oral BCL-XL/BCL-2 inhibitor, for the treatment of myelofibrosis, a rare blood cancer that develops when a genetic mutation occurs in blood stem cells, resulting in excessive scar tissue formation in the bone marrow.

“We are investigating if navitoclax may be an option that offers myelofibrosis patients a new level of disease management, including improved symptom control and potentially better treatment outcomes,” Zaki said in an AbbVie media release recently. These “anti-fibrosis efforts build on the company’s history of transforming standards of care in blood cancers with significant unmet needs,” he added.

Zaki tells Pharm Exec, “With Venclexta, Imbruvica, and now navitoclax, we are touching almost every hematologic malignancy that you can face.” He adds, with a smile, “We’re starting to run out of hematologic indications. What is left, other than very chronic, almost cured diseases?”

He has good reason to feel confident, though, especially when contrasting these advances with the cancer landscape he knew at the start of his career. “It’s a whole different world now. What we had back then in terms of treatment was chemo, chemo, chemo. People dying from chemo, people dying from disease. Now we see people living for a very long time,” he says. “What we’re aiming for in cancer now is a functional cure, where we transform acute malignancies to chronic ones. People will die from natural causes, not from their cancer. Cancer will be like diabetes, something you can live with.”

Zaki is excited about the growth of immuno-oncology, which was the subject of his PhD back in the 1990s. “To be able to go back to your own immune system to avoid chemotherapy, that is just magic,” he says. “Do you know how many years we’ve been talking about that in cancer therapy? Now we are finally able to do it.” The rise of immuno-oncology means more precise medicine, “which means you can treat the people who actually benefit from the drug.” Zaki explains, “When you think about a 30% response rate approval, what happened to the 70%? They’re taking a drug that doesn’t work for them. With more precise treatments, that response rate would increase to 90% or 100%. It’s very hard to do, of course; you have to find the right marker. A biomarker-driven approach is the key to this precision medicine that we’re pursuing.”

Among Zaki’s priorities at AbbVie now is to maximize the pipeline to get new treatments quickly to patients in need. “It’s about providing patients with options. Options are the name of the game with cancer; people live from drug to drug.”

There is a special urgency since COVID-19, which has been particularly hard on cancer patients. Zaki talks about patients, already immuno-compromised, that were simply too afraid to go to the hospital for their therapy. But he is proud that, during the pandemic, AbbVie’s oncology team was able to provide guidance to healthcare professionals (HCPs) to help them continue looking after cancer patients. The team “worked around the clock to continue educating HCPs and patient organizations on the latest data and best practices,” he says. AbbVie’s patient access and patient support system also helped patients to obtain their drugs and offered them financial support. And the increasing availability of oral medication for these diseases now meant that patients didn’t need to make a trip to the hospital.

The experience of leading his team during the disruption of the last 21 months has been a good one for Zaki. “It was about listening,” he says. “Employees were stuck at home and they wanted to talk. You have to be able to listen to them and remind them of the vital importance of what they do and what they bring to patients.” He adds, “I’m the sort of person who wants to see people, to be physically there with them, but we adapted well to Zoom meetings and maintained a good level of interaction.”

An unexpected benefit of going virtual, says Zaki, was the boost to recruitment. “People became extremely available, and not just because of virtual communication,” he observes. “They started to want change. That’s one of the impacts of COVID. People are realizing that life is too short to put up with an unrewarding job. They want to do something more meaningful.” Where Zaki says he used to hope to get one or two CVs when trying to recruit high-caliber people, all of a sudden he was getting 15.

Zaki also credits the attraction—and, just as importantly, retention—of good candidates to AbbVie to the company’s culture of inclusiveness. “From the moment I had my interview, I felt welcomed and respected at AbbVie,” he says. “If you work here, you feel this. The company really cares about its employees. We’re reminded every day about the importance of professional development, behavior development, succession planning, etc. It is a scientific culture of inclusiveness, a culture of respect for people, their family life, and work-life balance.”

While Zaki can look back on his and AbbVie’s efforts during the pandemic with a measure of pride, he was frustrated about how COVID derailed one of his favorite pastimes—travel. Fortunately, he had his other great hobbies, reading and watching sports, to occupy him during his extra free time. Zaki is a fan of basketball—he used to play back in Egypt—and he closely follows soccer, particularly the UK’s Premier League, where his countryman Mo Salah plays for Liverpool FC. But with travel being Zaki’s great passion, he felt trapped and helpless during COVID, like many of us. He says this, however, with his recognizable cheerfulness, so it’s difficult to believe his energy and enthusiasm were dampened too much by the restrictions of this period. He is quick to add that now that the borders are being opened, he’s very happy to be traveling again. In life, as in his work, the challenges and obstacles that Zaki faces are met—and overcome—with this enduring spirit of optimism.

Julian Upton is Pharm Exec’s European and Online Editor. He can be reached at jupton@mjhlifesciences.com.