Photo by Esther Dyson
Preparing drug for a trial
The US Food and Drug Administration (FDA) has granted orphan drug and fast track designations to tenalisib (RP6530) for the treatment of peripheral T-cell lymphoma (PTCL).
Tenalisib is a dual PI3K delta/gamma inhibitor being developed by Rhizen Pharmaceuticals.
Research has shown that tenalisib inhibits the growth of immortalized cancerous cell lines and primary leukemia/lymphoma cells.
In preclinical studies, tenalisib reprogrammed macrophages from an immunosuppressive M2-like phenotype (pro-tumor) to an inflammatory M1-like state (anti-tumor).
Researchers are currently conducting a phase 1 study of tenalisib in patients with relapsed/refractory PTCL. Results from this study were presented at the 2017 ASH Annual Meeting (abstract 2791*).
The presentation included data on 50 patients—24 with PTCL and 26 with cutaneous T-cell lymphoma (CTCL).
For the PTCL patients, the median age was 63 (range, 40-89), and 67% were male. The median number of prior therapies was 3 (range, 1-7). All patients had an ECOG status of 0 (n=14) or 1 (n=10). More patients had relapsed disease (n=17, 58%) than refractory disease (n=10, 42%).
For the CTCL patients, the median age was 67 (range, 37-84), and 46% were male. The median number of prior therapies was 5.5 (range, 2-15). All patients had an ECOG status of 0 (n=23) or 1 (n=3). More patients had refractory disease (n=15, 58%) than relapsed disease (n=11, 42%).
In the dose-escalation portion of the study, patients received tenalisib at 200 mg twice daily (BID), 400 mg BID, 800 mg BID fasting, or 800 mg BID fed. The maximum tolerated dose was 800 mg BID fasting, so this dose is being used in the expansion cohort.
Twelve PTCL patients were evaluable for efficacy. The overall response rate in these patients was 58% (7/12), with a 25% complete response rate (3/12).
Sixteen CTCL patients were evaluable for efficacy. The overall response rate was 56% (9/16). All responders had partial responses.
In both PTCL and CTCL patients, treatment-related grade 3 or higher adverse events (AEs) included transaminitis (22%), rash (6%), neutropenia (6%), hypophosphatemia (2%), increased international normalized ratio (2%), diplopia secondary to neuropathy (2%), and sepsis (2%).
Treatment-related serious AEs included sepsis, increased international normalized ratio, diplopia secondary to neuropathy, and pyrexia. Five patients discontinued treatment due to AEs.
About orphan and fast track designations
The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
The FDA’s fast track drug development program is designed to expedite clinical development and submission of new drug applications for medicines with the potential to treat serious or life-threatening conditions and address unmet medical needs.
Fast track designation facilitates frequent interactions with the FDA review team, including meetings to discuss all aspects of development to support a drug’s approval, and also provides the opportunity to submit sections of a new drug application on a rolling basis as data become available.
*Data in the abstract differ from the presentation.