FDA grants orphan status to Rafael Pharmaceuticals cancer drug

By Jenni Spinner

- Last updated on GMT

(rightdx/iStock via Getty Images Plus)
(rightdx/iStock via Getty Images Plus)

Related tags Cancer Oncology Rare disease Orphan drug Fda FDA approval

The company’s cancer drug, devimistat, has received orphan status from the agency for treating clear-cell sarcoma, pancreatic cancer, and other diseases.

Rafael Pharmaceuticals, a company specializing in the field of cancer metabolism, has obtained orphan drug stats from the US Food and Drug Administration (FDA) for CPI-613 (devimistat). Outsourcing-Pharma (OSP) recently chatted with president and CEO Sanjeev Luther about the development, its work on rare cancers, and other achievements.

OSP: Please tell us about relapsed/refractory clear-cell sarcoma—how rare is this condition, and what types of therapeutic options have historically been available for patients diagnosed with it? 

SL: Clear cell sarcoma is a type of rare soft tissue sarcoma which often affects young adults between the ages of 20 and 40, in the limbs of a person's body from legs to arms. Clear cell sarcoma makes up 1% of sarcoma cases.

Treatment options typically include chemotherapy and surgical resection. Rafael’s Phase 2 clinical trial is now bringing cancer metabolism into the fold, using devimistat in combination with hydroxychloroquine to treat patients with clear cell sarcoma of soft tissue.

OSP: Why is exploration of treatment options for rare/orphan diseases important? 

SL: Orphan diseases have a patient population of less than 200,000 nationwide. Due to the rarity of the disease it is more difficult for clinical trials to be conducted, which is partially why there is a significant lack of treatment options available.

We have a saying: to save a life is to save a universe. This is one of the many reasons we partnered with Sara’s Cure, an organization founded by Lennie Woods to help her daughter Sara after she was diagnosed. There are people like Sara across the world, looking for a treatment that will work for them. In conjunction with Sara’s cure and the Sarcoma Alliance for Research through Collaboration (SARC) we hope to bring further treatment options to this population.

OSP: Could you please tell us about CPI-613/devimistat?

Sanjeev Luther, president and CEO, Rafael Pharmaceuticals

SL: Devimistat was discovered at Stony Brook University, designed to target the mitochondrial tricarboxylic acid (TCA) cycle, an indispensable process essential to tumor cell multiplication and survival, selectively in cancer cells. Devimistat targets two enzymes that are indispensable to the altered metabolism of tumor cell mitochondria and because the drug has two targets, efficacy is increased and the likelihood that cancer cells will become resistant is reduced, making devimistat the strongest metabolic drug now under development. In layman's terms, devimistat targets the reproduction of cancer cells and staves them.

The FDA has given Rafael approval to initiate pivotal Phase 3 clinical trials in pancreatic cancer (AVENGER 500) and acute myeloid leukemia (ARMADA 2000), and has designated devimistat as an orphan drug for the treatment of pancreatic cancer, acute myeloid leukemia, myelodysplastic syndrome, peripheral T-cell lymphoma, Burkitt’s lymphoma and soft tissue sarcoma. The European Medicines Agency has granted orphan drug designation to devimistat for pancreatic cancer and acute myeloid leukemia.

OSP: What can you tell us about the decision to explore the possibilities of combining devimistat with hydroxychloroquine? 

SL: In a preclinical setting, it was found that devimistat, which targets tumorous mitochondrial energy metabolism, induced autophagosome formation followed by lysosome fusion in HS-MM CCS cells in vitro. Interestingly, devimistat along with chloroquine, which inhibits the fusion of autophagosomes with lysosomes, significantly induced necrosis of HS-MM CCS cell growth in vitro.

Subsequently, we established a murine orthotopic metastatic model of CCS and evaluated the putative suppressive effect of a combination of CPI613 and chloroquine on CCS progression. Injection of HS-MM into the aponeuroses of the thigh, the most frequently affected site in CCS, resulted in massive metastasis in SCIDbeige mice.

By contrast, intraperitoneal administration of devimistat (25 mg/kg) and chloroquine (50 mg/kg), two days a week for two weeks, significantly decreased tumor growth at the injection site and abolished metastasis. The present results imply the inhibitory effects of a combination of devimistat and chloroquine on the progression of CCS

OSP: What kinds of unique challenges has the COVID-19 pandemic created in your work, on this and other projects? 

SL: The COVID-19 pandemic has created unique challenges when conducting clinical trials, in fact, 1,099 clinical trials were suspended, discontinued or withdrawn due to the pandemic. Because our patients do not have time to wait for the virus to subside, we immediately established a COVID-19 task force to closely monitor our clinical trials and make changes as needed in order to support our clinical trial sites and enrolled patients. This means keeping close with every single clinical trial site to preempt and promptly address any potential challenges. Each clinical trial site has implemented their own safety measures based on guidelines from local authorities.

Overall, these processors have allowed us not only to keep the trial running but hit milestones such as our enrollment of 500 patients in our Phase 3 pancreatic cancer clinical trial, launching a Phase 1 pancreatic clinical trial in Japan and achieving milestone enrollment of 100 patients in our Phase 3 acute myeloid leukemia clinical trial.

OSP: What else would you like to add that we didn’t touch upon above?

SL: One in three people will be diagnosed with cancer in their lifetime. Immunotherapies and chemotherapy have done phenomenal work to the prolongment of life and the treatment of many cancers and now it’s time to turn to other options, like cancer metabolism.

We have continued to pull in lead principal investigators and physicians from top institutions across the globe, to provide patients the best clinical trial treatment options possible. We are deeply appreciative of these clinicians and our partners like Sara’s Cure, SARC and the FDA for helping us get to where we are today.

We also appreciate our patients who are true pioneers in helping us develop this treatment. For those who are looking for a clinical trial near them, they can visit our trial page​.

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