“The challenges for cancer drug development are late-stage failures and limited clinical efficacy. This will not be different for this company,” said Dr Beijersbergen. “The major costs for drug development are in the late phases of clinical trials with large numbers of patients. Again, this will not be different from [the pharmaceutical industry].”

This isn’t the first time a research team has approached drug development from a me-too angle, but what does potentially make EQRx’s goal noteworthy is actually its lack of specificity. Rather than match up 1 existing compound with 1 new biological target — like using NSAIDs to treat head and neck cancer or statins to stymie metastatic breast cancer — its target is oncology at large, not, say, lung cancer (it also plans to target immuno-inflammation and rare diseases). Focusing on repurposing non-oncology drugs for oncological targets could be a boon in that regard, based on recent findings.

A January 2020, Nature Cancer found that dozens of non-oncology drugs are effective at killing cancer cells,1 and sometimes in unexpected ways, showing that this type of repurposing has vast potential beyond a case-by-case basis, where it has already been successfully applied.

“We thought we’d be lucky if we found even a single compound with anticancer properties, but we were surprised to find so many,” said Todd Golub, MD, chief scientific officer and director of the Broad Institute’s Cancer Program, Massachusetts, in a statement.2

Dr Beijersbergen, too, espoused this concept. “The identification of non-oncology drugs as potential new strategies to treat cancer open up the possibility to explore novel cellular pathways and mechanisms as cancer vulnerabilities,” he wrote in an editorial.3 “The use of non-oncology drugs can also be valuable in the identification of novel effective combinations with existing cancer drugs to enhance their effects or to prevent or revert resistance.”

This promising area of so-called drug development, which would shift the focus toward looking more closely at what we already have and how it might serve multiple purposes — rather than reinventing the wheel for each new disease — is a familiar concept to David Fajgenbaum, MD.

Dr Fajgenbaum, who is an assistant professor at the Perelman School of Medicine of the University of Pennsylvania, was diagnosed with idiopathic multicentric Castleman disease — which he calls “a strange chimera of lymphoma and autoimmunity” — and it was initially quelled by chemotherapy. The disease came back in 4 subsequent relapses over 3 years while he was on the only drug clinically indicated for his condition.

So Dr Fajgenbaum, who is also a cofounder and the executive director of the Castleman Disease Collaborative Network, turned to self-experimentation. He found that a key signaling pathway that regulates the cell cycle was hyperactive in his body, a complication also shared with some people who have undergone kidney transplantation. Thus, an effective drug developed for this problem as it presents in the latter population might inhibit similar cellular behavior caused by his disease, he thought. It’s now been over 6 years since his last relapse.

A key message from Dr Fajgenbaum’s story is not just about the science behind the medication he selected for himself, though. It’s also about the pipeline issues — some of which are the result of the existing regulatory processes inherent to the US Food and Drug Administration (FDA) — that caused him to turn to drug repurposing in the first place. 

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“Developing a new FDA-approved drug takes 10-15 years and over $1 billion. Clearly, I didn’t have that kind of time or money,” he said. “Fortunately, there are more than 1500 drugs that are already FDA-approved for at least 1 condition. Many diseases share similar dysfunctional cell types, genes, communication lines, and proteins, so I understood that many drugs could theoretically be used ‘off label’ to effectively treat diseases with no other options.”

If EQRx finds success, it will likely be through the codifying and streamlining of this side-door option. Perhaps the most innovative thing it could do would be to not make anything new at all.

It’s the pathway itself — to getting the best medicine into the right hands at the lowest cost — that has the most potential for success, according to Dr Fajgenbaum.

“New oncology drugs are priced at very expensive levels, but if a drug is already FDA-approved for a non-oncology condition, then the drug is likely to be much less than what it would have cost if it were originally approved for an oncologic disease,” he said.

References

  1. Corsello SM, Nagari RT, Spangler RD, et al. Discovering the anticancer potential of non-oncology drugs by systematic viability profiling. Nat Cancer. 2020;1(2):235-248.
  2. Dozens of non-oncology drugs can kill cancer cells. Broad Institute. https://www.broadinstitute.org/news/dozens-non-oncology-drugs-can-kill-cancer-cells. Published January 20, 2020.
  3. Beijersbergen RL. Old drugs with new tricks. Nat Cancer. 2020;1(2):153-155.