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The FDA has yet to approve Bristol-Myers Squibb and Karuna Therapeutic A long-awaited treatment for schizophrenia But KarXT is already facing potential competitive threats as its decision date nears.
KarXT, a combination of xanomeline and trospium, is taken twice a day, so New York-based Terran Biosciences hopes to gain an edge by improving the dosing schedule. Once-daily tablet “TerXT” and long-acting injectable “TerXT LAI”.
But that’s not the only differentiator.
“This is not a new formulation of KarXT, it’s an entirely new drug. Prodrug “It’s a combination of xanomeline and trospium,” said Dr. Sam Clark, founder and CEO of Terran.
Theran’s drugs are new prodrugs that become effective once inside the body, and because xanomeline and trospium are decades old and off patent, Theran also hopes to circumvent the traditional patent period.
“Prodrugs can block it if the original ingredient is still there, but it’s no longer there,” Clark said.
Although the FDA typically considers prodrugs to be new chemical entities, Terran could use data from testing it conducted on the parent molecule to gain fast track approval. However, it would have to wait five years of marketing exclusivity from BMS before it could deliver the product to consumers. Still, Terran could potentially take some of KarXT’s share of the schizophrenia market. $7.11 billion by 2028 — five years before the patent expires, which could be a boon for people suffering from this highly debilitating disease. Better treatments are desperately needed.
Potential blockbuster for schizophrenia
KarXT has high hopes for the drug, which could be the first new type of drug available to people with schizophrenia in decades.
Bristol-Myers Squibb acquired KarXT as part of its $14 billion deal with Karuna. December 2023Analysts predict the drug will: Reach $10 billion Peak sales are potential Bright spot As the September 26 PDUFA deadline approaches, new momentum is emerging in the company’s portfolio growth plans.
Muscarinic agonists have generated a lot of excitement because they appear to help treat a wide range of schizophrenia symptoms without the debilitating side effects of traditional antipsychotics. 70% Many people with schizophrenia abandon treatment, which can result in side effects such as weight gain, metabolic syndrome, or tardive dyskinesia, an involuntary movement disorder.
If successful, Theran’s once-a-day pill, or a single injection over several months, could provide similar benefits to patient populations who struggle with adherence, and the company’s prodrug could also help lower the cost of treatment.
“We don’t know exactly what KarXT will cost, but when there’s only one antipsychotic drug or one product on the market, it’s typically more expensive than if there are multiple different versions of that original molecule,” Clark said.
Scientific Challenges
Developing prodrugs of zanomeline and trospium was no easy task for Teran, and experts were initially skeptical, Clark said.
“When we brought this to our scientific team, we had to develop some new strategies,” he said. “It took two years and at one point we had 200 full-time chemists. We made 700 prodrugs.”
The large-scale effort comes as the company works to develop drugs in mid-stage development. Idazoxaneplivanserin and vorinanserin, selective serotonin 2A receptor antagonists licensed from French pharmaceutical company Pierre Fabre Médicament for the treatment of schizophrenia and Alzheimer’s disease; Licensed from Sanofi To treat a variety of neuropsychiatric disorders.
“We want to ensure patients have rapid access to the latest technology.”
Dr. Sam Clark
CEO and Founder of Terran Biosciences
Improved versions of drugs typically don’t reach the market until 10 to 15 years after they were first introduced, often as an attempt by companies to maintain market share as patents expire, Clark said.
“We saw this with Otsuka Pharmaceutical’s new long-acting injectable Abilify. When the patent expired, the company switched from a once-monthly prescription to a new version taken once every two months. The company expected to lose a lot of revenue, so it upgraded to the new version to keep its branded product in the market,” he said.
Teran aims to get ahead of BMS by bringing potentially improved options to patients sooner.
“We want to give patients immediate access to the latest technology, and in the past with antipsychotics this has sometimes been delayed,” Clark said.
Clark said company executives are confident in their plans, but questions remain, the biggest being whether the prodrug formulation, still in preclinical development, will work as expected.
“We haven’t administered it to humans, so we can’t say our product is automatically better,” Clark says, “but our goal is to improve, and so far in the animal models we’ve seen improvements over the original xanomeline and trospium studies.”
Company officials also need to meet with the FDA to determine the feasibility of using an expedited approval process so they can act if KarXT is approved.
“The FDA’s 505(b)(2) pathway allows drug developers to reference trial data from an approved parent molecule. This approach still requires a pharmacokinetic bridging study (phase 1), but may not require large-scale efficacy studies (phase 2/3) for approval,” Clark said in an emailed statement. “Teran plans to initiate a PK bridging study comparing the PK of TerXT to KarXT shortly after BMS receives FDA approval of KarXT.”
