How One Biotech Is Using FDA 505(b)(2) To Get Drugs To Patients Quicker And Cheaper
A conversation with Terran Biosciences CEO Sam Clark, MD, Ph.D.
Terran Biosciences has been patiently awaiting the FDA approval of Bristol Meyers Squibb’s Cobnefy (xanomeline and trospium chloride), the first new drug to treat schizophrenia in more than 30 years . And when the FDA gave it the OK, Terran was one of the first to celebrate.
It might sound strange that a biotech would applaud the approval of a lead asset by Big Pharma, but the approval means Terran can now forge ahead with a 505(b)(2) for its own therapy, TerXT.
Terran CEO Sam Clark, MD, Ph.D. explains how his team is leveraging this particular regulatory pathway to get its own therapy to patients quickly and affordably.
Tell us about the 505(b)(2) pathway and how Terran is using it to get drugs to patients quicker and cheaper.
With the 505(b)(2) pathway, after a company gets a drug approved, the FDA allows others to reference that data to get new drugs approved through inexpensive “bridging” toxicology and pharmacology studies. This saves a significant amount of time and cost, as it eliminates the need to repeat the large and expensive Phase 2 and Phase 3 efficacy trials conducted with the first drug to get approval.
The 505(b)(2) pathway has been widely utilized with antipsychotics to bring longer-acting forms of these drugs to market. Notable examples include the long-acting injectables (LAIs) Aristada and Asimtufii as well as several long-acting forms of risperidone. The 505(b)(2) pathway is very important for patients because having multiple drugs on the market increases the number of options available for patients and contributes to more affordable pricing. Improving the patient experience by providing new and improved treatment options and increasing access to affordable medications is incredibly important to us at Terran.
One example where we have been actively preparing for 505(b)(2) applications is in the development of psychedelic therapeutics for mental illnesses, including depression and anxiety. Here we've created new forms of psilocybin and MDMA, and we were recently awarded U.S. patents confirming they are the first novel forms of these drugs. We intend to pursue the 505(b)(2) approval path for both MDMA and psilocybin after these drugs are first approved in the US, which we believe will lead to additional cost-effective treatments on the market to benefit patients.
So, it allows you to piggyback on a drug that already exists?
All scientific research involves building on the work of other researchers. We believe that the ability to use data generated by other companies to accelerate drug development is a very positive outcome for patients and our healthcare system. Patients need access to improved medications at affordable prices and the 505(b)(2) pathway was designed to eliminate wasteful spending and incentivize innovation to accelerate the drug development process.
Are you in good company or are you rogue with that approach?
The 505(b)(2) pathway is not new and has been widely used across all therapeutic areas including neuroscience, notable examples include the antipsychotics Aristada and Asimtufii which referenced the data generated by the original drug, Abilify. Similarly, the antipsychotics Uzedy, Rykindo, and Risvan all used Risperdal as the original drug of reference.
In particular, you’re using this approach to take on Bristol Meyer Squibb’s Cobenfy (formerly KarXT) with TerXT. What’s unique about this situation?
TerXT is our lead program and it takes into account expertise gained from all of our other programs. Cobenfy is composed of two old molecules, xanomeline invented in the 1990s, and trospium chloride invented in the 1960s. This combination showed great efficacy and safety in Phase 3 trials in patients with schizophrenia and was recently approved, making it the first drug with a new mechanism to treat schizophrenia in at least 50 years. However, some of the limitations with Cobenfy are that it has to be taken twice daily, it can’t be taken with food, and there is no long-acting injectable (LAI) version. This is in contrast to other antipsychotics on the market which are typically taken once daily and have LAI versions that, in some cases, only need to be dosed once every 3-6 months.
At Terran, we are experts in fixing drugs with pharmacological issues. For example, we've previously turned a three-times-a-day antipsychotic drug, idazoxan, into a once-daily drug. Similarly, we noticed some of the issues faced by Cobenfy’s active ingredients xanomeline and trospium, and saw an opportunity to develop a once-daily oral dose and also an LAI with a multi-month duration using a novel prodrug approach.
A prodrug is an inactive molecule that becomes active after it is absorbed into the body. This involves modifying the original molecule with an inert side chain that helps it absorb into the body where the side chain is then metabolized by enzymes in the blood releasing the original molecule to act on the brain. The FDA views prodrugs as potential 505(b)(2) candidates, so we designed an extensive prodrug development program to enable the once-daily oral dose and the long-acting injectable prodrug forms of xanomeline and trospium, which we call “TerXT.” This strategy has shown great success across the antipsychotic landscape, and some of the leading antipsychotics on the market (such as Invega and Abilify) have been improved into LAIs through prodrugs.
How long will it take for TerXT to reach the market?
In the examples of other approved antipsychotics previously mentioned, the prodrugs were brought to market over a decade after the first drug was approved. At Terran, we believe that patients shouldn't have to wait for the newest technology so we moved quickly to make TerXT. Now that Cobenfy is approved, we are moving rapidly toward clinical trials and plan to submit our 505(b)(2) application for approval as soon as the typical five-year exclusivity period expires.
About The Expert:
Sam Clark, MD, Ph.D., founder and CEO of Terran Biosciences, is a multi-published neuroscientist and innovator with over 200 patent applications. With MD and Ph.D. degrees from Columbia University and a BS in neuroscience from MIT, he founded Terran Biosciences to create a platform biotech company to transform the approach to therapeutics in neuropsychiatry. At Terran, he has created one of the largest psychedelic development programs in the industry and has become a leader in medicinal and synthetic chemistry and novel approaches to the improvement and optimization of therapeutic compounds for patient use. You can connect with Sam on LinkedIn and X.