FDA Grants Orphan Drug Designation to OTX-2002 in HCC


OTX-2002 has received an orphan drug designation by the FDA for patients with hepatocellular carcinoma. The agent will further be evaluated in the phase 1/2 MYCHELANGELO trial.

The FDA has granted an orphan drug designation to OTX-2002, a first-in-class epigenomic controller, for the treatment of patients with hepatocellular carcinoma (HCC).1

OTX-2002 is an mRNA therapeutic given to patients via lipid nanoparticles. The agent downregulates MYC expression pre-transcriptionally through epigenetic modulation while working to overcome MYC autoregulation. MYC is a master transcription factor which works to regulate cell proliferation, differentiation, and apoptosis. Further, MYC plays a significant role in more than 50% of all human cancers.

Currently, OTX-2002 is being evaluated both as a single agent and in combination with a TKI or PD-(L)1 inhibitor in the phase 1/2 MYCHELANGELO I trial (NCT05497453) of patients with relapsed or refractory HCC and other solid tumor types known for association with the MYC oncogene.2

“HCC is a devastating illness that often develops resistance to current standard of care therapeutics. The FDA’s decision to grant orphan drug designation for OTX-2002 underscores the need for novel therapies to address HCC and the potential of epigenetic programming to transform the treatment landscape,” said Mahesh Karande, president, and chief executive officer of Omega Therapeutics, in a press release.

Recently, the company announced that the first patient had been dosed in the trial. In the study, patients aged 18 years and older with metastatic, advanced, or recurrent solid tumors that progressed on, relapsed after, became refractory to, or developed intolerance to standard of care therapy will be enrolled.

Patients must also have an ECOG performance status of 0 or 1, BCLC stage B or C, Child-Pugh A HCC whichis not amenable to locoregional therapy, refractory to locoregional therapy, or not amenable to curative treatment approach, have progressed on, have relapsed after, be refractory to, or be intolerant of at least 1 prior systemic therapy, and be without available subsequent standard of care treatment in order to be included in the trial. Moreover, patients with chronic hepatitis B are required to have received antiviral therapy for hepatitis B virus (HBV) for12 weeks or more. These patients must also have an HBV viral load below 500 IU/mL before the first dose of the study drug.

Those enrolled will receive treatment in 1 of 4 cohorts and OTX-2002 will be administered via intravenous infusion over 80 to 120 minutes every 2 weeks. Part 1 of the trial will include OTX-2002 monotherapy and part 2 will evaluate OTX-2002 combined with standard of care in patients with HCC.

The design of part 1 of the trial is a dose-escalation and -expansion, and part 2 consists of safety run-in and expansion. The primary end points being investigated in the study are to determine the maximum tolerated dose of treatment, dose-limiting toxicities, incidence of treatment-emergent adverse events, overall response rate, and duration of response.

“We look forward to continuing to work with clinical investigators, patients and the FDA as we advance our MYCHELANGELO clinical program and evaluate the potential of OTX-2002 to bring a new treatment option to the liver cancer patient community,” concluded Karande.

  1. Omega Therapeutics receives orphan drug designation for OTX-2002 for the treatment of hepatocellular carcinoma. News release. Omega Therapeutics, Inc. November 2, 2022. Accessed November 2, 2022. https://prn.to/3NwgygD
  2. A phase 1/2 study to evaluate OTX-2022 in patients with hepatocellular carcinoma and other solid tumor types known for association with the MYC oncogene (MYCHELANGELO I). ClinicalTrials.gov. Updated August 24, 2022. Accessed November 2, 2022. https://www.clinicaltrials.gov/ct2/show/NCT05497453?term=omega&cond=Hepatocellular+Carcinoma&draw=2&rank=1
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