CURx Pharmaceuticals Announces New Topiramate Injection Data Presented at 9th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures Conference
Captisol-enabled™ Topiramate Injection shown to be a substitute for an oral dose on a one-to-one basis
LONDON, April 8, 2024 – CURx Pharmaceuticals Incorporated today announced that its partners at the University of Minnesota (UMN) and Ligand Pharmaceuticals, Inc. presented new data on Captisol-enabled™ Topiramate Injection (IV topiramate), a potential
replacement therapy for the treatment of certain emergent neurological conditions, including epilepsy, when oral administration is not feasible.
The poster was featured at the 9th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures Conference in London, England. The authors presented modeling and simulations of IV topiramate dosing based on previous studies conducted by UMN faculty in healthy research participants and patients. In addition, preliminary pharmacokinetic data was presented from 25 healthy participants in a CURx ongoing randomized, single-center, open-label, cross-over clinical study for an investigational intravenous (IV) formulation of topiramate, an antiseizure and anti-migraine medication.
“The IV formulation of topiramate can be used as replacement therapy; but additionally, small studies in neonates and patients with prolonged seizures indicate it may have a role in treating these conditions if future studies demonstrate benefit,” said James Cloyd, Pharm.D., Director of the Center for Orphan Drug Research at the University of Minnesota College of Pharmacy, co-author of the poster, and a principal investigator on several IV topiramate studies. “Based on our research, we believe clinicians can now properly dose IV topiramate in a variety of clinical situations, including the use of loading doses to rapidly attain targeted plasma drug concentrations in patients when there is a delay in initiating replacement therapy, in patients who are getting topiramate for the first time, and in those taking a co-medication that increases the elimination of topiramate.”
“This poster incorporates preliminary pharmacokinetic data from our recent study in healthy research subjects in which an intravenous dose of topiramate was compared to a dose of oral topiramate to assess safety and the dose of the IV topiramate needed to replicate the plasma concentrations following oral administration,” commented Bernard King, M.D., Chief Medical Officer of CURx and co-author of the poster. “Our findings confirm that IV topiramate can be substituted for an oral dose on a one-to-one basis, thus simplifying replacement therapy.”
IV topiramate is an investigational formulation of topiramate designed for the treatment of partial onset or primary generalized tonic-clonic seizures in hospitalized epilepsy patients and treatment of epilepsy patients in an emergency care setting who are unable to take oral topiramate. Ligand licensed the rights to the IV formulation of topiramate from UMN and entered into a global license agreement with CURx Pharmaceuticals to further develop and commercialize the product. IV topiramate has been granted Orphan Drug Designation by the U.S. Food and Drug Administration and Ligand is entitled to net milestone payments and a mid-single-digit royalty on global sales.
“Our longtime partners are making much-needed progress for people managing epilepsy, and it is exciting to see that,” said James Pipkin, Ph.D., Vice President of New Product Development at Ligand. “The availability of an injectable topiramate formulation will make it possible to ensure continuity of therapy. Captisol is what enables this and other new formulations, which give patients more options and flexibility when it comes to maintaining their medication regimens.”
Abstract 305 “A Comparison of IV and Oral Topiramate Pharmacokinetics in Healthy Participants, Patients with Migraines, and Patients with Epilepsy with or without Concomitant Enzyme-Inducing Drugs” was presented by the poster co-authors at the University of Minnesota College of Pharmacy.
April 2024
CURx has completed the Phase 1 Pivotal Trial for the first and only IV formulations of Anti-Epileptic Drug Topiramate. The results have been analyzed and we anticipate NDA submission to the FDA in the 4th Quarter of 2024 and marketing approval in the US in late 2025. The product uses Captisol (Cydex Pharma/ Ligand) to solubilize topiramate. Captisol has been successfully used to solubilize several products including products marketed by Merck, Pfizer and Gilead.
Pivotal Trial was initiated in January 2024; last subject last dose was administered in April 2024, trials being performed by Medpace, CRO in their Phase 1 Unit in Cincinnati, OH.
Epilepsy is the fourth most common neurological disorder in the United States (after Alzheimer disease, migraine, and stroke). It affects 3.4 million individuals (approximately 3 million adults and 400,000 children). The annual incidence (new cases) of epilepsy in the US is approximately 68 per 100,000 population or approximately 250,000.
On those occasions when the patient with epilepsy is unable to continue their usual oral regimen, intravenous formulations of the patient’s AEDs provide a smooth bridging transition through that period back to oral therapy. There is no approved IV formulation of topiramate currently available.
At present, topiramate is indicated:
· As initial monotherapy for the treatment of partial-onset or primary generalized tonic-clonic seizures in patients 2 years of age and older,
· As adjunctive therapy for the treatment of partial-onset seizures, primary generalized tonic-clonic seizures, and seizures associated with Lennox-Gastaut syndrome in patients 2 years of age and older and
· For the preventive treatment of migraine in patients 12 years of age and older.
The current recommended dose for individuals with epilepsy is 200-400 mg per day in two divided doses and for migraine prophylaxis is 100 mg per day in two divided doses. Of the approved AED’s Topiramate has one of the widest labels with no black box warning.
09/09/14: CURx Pharmaceuticals, Inc. licenses Captisol enable Lamotrigine from Ligand Pharmaceuticals
SAN DIEGO–(BUSINESS WIRE)– Ligand Pharmaceuticals Incorporated (NASDAQ: LGND) announced it has expanded its global license agreement with CURx Pharmaceuticals, Inc. to also include the development and commercialization of Ligand’s Captisol-enabled™ Lamotrigine program. Under the terms of the expanded license, Ligand will be eligible to receive $22 million in potential milestone payments, revenue from the sales of Captisol, and tiered royalties on future net sales in the range of 4% to 7% for Captisol-enabled™ Lamotrigine. CURx will be responsible for all costs related to the program.
“This is Ligand’s second program licensed to CURx and is another example of the importance of our Captisol® formulation technology to enable new and highly differentiated programs. We are pleased that our relationship with CURx has expanded with the licensing of Captisol-enabled™ Lamotrigine, a product candidate targeting hospital-based seizures,” commented John Higgins
, President and Chief Executive Officer of Ligand. “Captisol-enabled™ Lamotrigine adds to our growing pipeline of over 100 partnerships.”
Dinu Sen
, CEO and founder of CURx, commented, “We are delighted to report expansion of our portfolio of development products to three, including our second Captisol-enabled™ anti-epileptic drug. Consistent with our development plans for Captisol-enabled Topiramate, our goal is to develop this IV formulation of lamotrigine as a bridging therapy for patients with epilepsy who are temporarily unable to take oral lamotrigine.”
About Captisol-Enabled™ Lamotrigine
Captisol-enabled™ Lamotrigine was specifically formulated by Ligand to provide an intravenous or intramuscular option for hospitalized patients unable to use oral lamotrigine. Lamictal® (lamotrigine) is approved as adjunctive therapy in patients with partial seizures, adjunctive treatment of generalized seizures of Lennox-Gastuat syndrome and maintenance treatment of Bipolar I disorder. Captisol-enabled™ Lamotrigine is currently in pre-clinical development. Lamictal® and Lamictal® XR™ are marketed by GlaxoSmithKline. Lamictal® lost patent exclusivity in 2009.
About Captisol®
Captisol is a patent-protected, chemically modified cyclodextrin with a structure designed to optimize the solubility and stability of drugs. Captisol was invented and initially developed by scientists in the laboratories of Dr. Valentino Stella
at the University of Kansas’ Higuchi Biosciences Center for specific use in drug development and formulation. This unique technology has enabled six FDA-approved products, including Onyx Pharmaceuticals’ Kyprolis®
, Baxter International’s Nexterone®
and Merck’s Noxafil®
IV. There are currently more than 50 Captisol-enabled products in development, including Lundbeck’s Carbella™, Spectrum Pharmaceuticals’ Captisol-enabled Melphalan and Melinta Therapeutics’ delafloxacin IV program.
About CURx Pharmaceuticals, Inc.
CURx Pharmaceuticals develops therapeutics to provide effective solutions to currently unmet needs of patients with chronic diseases. CURX has licensed three mid- to late-stage molecules that fulfill our criteria for further development. These criteria include sound scientific rationale, strong preclinical and clinical study results, defined regulatory pathway to approval and robust IP protection. CURx Pharmaceuticals’ lead clinical asset is Fosfomycin Tobramycin for Inhalation (FTI), which is being developed as a treatment for patients with Cystic Fibrosis. CURx is committed to serving patients with innovative and differentiated therapeutics that will improve their quality of life and clinical outcome.
About Ligand Pharmaceuticals
Ligand is a biopharmaceutical company with a business model that is based upon the concept of developing or acquiring royalty revenue generating assets and coupling them to a lean corporate cost structure. Ligand’s goal is to produce a bottom line that supports a sustainably profitable business. By diversifying our portfolio of assets across numerous technology types, therapeutic areas, drug targets and industry partners, we offer investors an opportunity to invest in the increasingly complicated and unpredictable pharmaceutical industry. In comparison to its peers, we believe Ligand has assembled one of the largest and most diversified asset portfolios in the industry with the potential to generate revenue in the future. These therapies address the unmet medical needs of patients for a broad spectrum of diseases including diabetes, hepatitis, muscle wasting, Alzheimer’s disease, dyslipidemia, anemia, asthma and osteoporosis. Ligand’s Captisol platform technology is a patent protected, chemically modified cyclodextrin with a structure designed to optimize the solubility and stability of drugs. Ligand has established multiple alliances with the world’s leading pharmaceutical companies including GlaxoSmithKline, Onyx Pharmaceuticals (a subsidiary of Amgen Inc.), Merck, Pfizer, Baxter International, Eli Lilly & Co., Spectrum Pharmaceuticals and AstraZeneca. Please visit www.captisol.com for more information on Captisol. For more information on Ligand, please visit www.ligand.com. Follow Ligand on Twitter @Ligand_LGND.
Forward-Looking Statements
This news release contains forward-looking statements by Ligand that involve risks and uncertainties and reflect Ligand’s judgment as of the date of this release. These include statements regarding clinical development of Captisol-enabled Lamotrigine, possibility of commercial success, efficacy, potency, competitiveness and the strength of Ligand’s product portfolio. Actual events or results may differ from our expectations. For example, there can be no assurance that Captisol-enabled Lamotrigine will progress through clinical development or receive required regulatory approvals within the expected timelines or at all, that further clinical trials will confirm any safety or other characteristics or profile, that there will be a market of any size for Captisol-enabled Lamotrigine or that Captisol-enabled Lamotrigine will be beneficial to patients or successfully marketed. The failure to meet expectations with respect to any of the foregoing matters may have a negative effect on Ligand’s stock price. Additional information concerning these and other risk factors affecting Ligand’s business can be found in prior press releases available via www.ligand.com as well as in Ligand’s public periodic filings with the Securities and Exchange Commission at www.sec.gov. Ligand disclaims any intent or obligation to update these forward-looking statements beyond the date of this release. This caution is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995.
Source: Ligand Pharmaceuticals Incorporated
Ligand Pharmaceuticals Incorporated
John Higgins, President and CEO
(858) 550-7500
@Ligand_LGND
08/14/13: Ligand Enters Global License Agreement with CURx Pharmaceuticals, Inc. for Captisol-EnabledTM Topiramate Injection
SAN DIEGO–(BUSINESS WIRE)– Ligand Pharmaceuticals Incorporated (NASDAQ: LGND) announces it has entered a global license agreement with CURx Pharmaceuticals, Inc. for the development and commercialization of Ligand’s Captisol-enabled™ Topiramate Injection for the treatment of partial onset or primary generalized tonic-clonic seizures in hospitalized epilepsy patients who are unable to take oral topiramate. Under the terms of the agreement, Ligand will be eligible to receive more than $21 million in potential net milestone payments and net royalties on future sales of 6.0% to 7.5%.
“This is another great deal for Ligand and our Captisol technology, pairing our proven formulation agent with an approved medicine to create a potentially novel, important and highly differentiated drug,” commented John Higgins, President and Chief Executive Officer of Ligand. “We are very pleased to be entering this agreement. CURx is highly motivated to advance development with current plans calling for a Phase II trial to commence in 2014. This deal represents our latest addition to our growing pipeline of partnerships and another potentially lucrative shot-on-goal.”
Dinu Sen, Chief Executive Officer and founder of CURx, said of this transaction, “We are delighted to sign a licensing agreement with Ligand and plan to bring Captisol-enabled Topiramate Injection to our patients as soon as possible. In Phase I trials in healthy volunteers and patients at the University of Minnesota, the product demonstrated a faster onset of action than the orally administered drug. Our market research indicates there to be a tremendous need for a product with these characteristics.”
07/26/13: Ligand Receives Orphan Designation for Captisol-EnabledTM Topiramate Injection
SAN DIEGO–(BUSINESS WIRE)– Ligand Pharmaceuticals Incorporated (NASDAQ: LGND) announced that the U.S. Food and Drug Administration (FDA) has granted orphan-drug designation for its proprietary Captisol-enabled™ Topiramate Injection for the treatment of partial onset or primary generalized tonic-clonic seizures in hospitalized epilepsy patients who are unable to take oral topiramate.
“The granting of orphan designation for Ligand’s Captisol-enabled Topiramate program is an important step in the future of this potentially life-saving therapeutic, and should provide an additional layer of market exclusivity for the program,” commented Matthew W. Foehr, Executive Vice President and Chief Operating Officer of Ligand. “In Phase 1 trials in healthy volunteers and patients at theUniversity of Minnesota, this product demonstrated a faster onset of action than the orally administered drug. Our goal is to find a committed partner to further progress the clinical development of this asset and add to our portfolio of fully-funded programs.”
“An injectable formulation of Topiramate will provide patients and clinicians with an important new product that ensures continuity of therapy and offers the potential for use in acute management of several neurological disorders,” declared Jim Cloyd, Pharm.D., Lawrence C. Weaver Endowed Chair in Orphan Drug Development, Professor of Experimental and Clinical Pharmacology and Director of the Center for Orphan Drug Research at the University of Minnesota-College of Pharmacy.
Orphan-drug designation is granted to drugs and biologics defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases/disorders that affect fewer than 200,000 people in the U.S., or that affect more than 200,000 persons but are not expected to recover the costs of developing and marketing a treatment drug.