Ligand Partners Spectrum Pharmaceuticals & Lundbeck Receive FDA Approvals

Ligand Pharmaceuticals Incorporated recently announced that partner Spectrum Pharmaceuticals, Inc., a biotechnology company with fully integrated commercial and drug development operations with a primary focus in hematology and oncology, received approval from the US FDA of EVOMELA™ (melphalan) for use in two indications: 1) as a high-dose conditioning treatment prior to hematopoietic progenitor (stem) cell transplantation (ASCT) in patients with MM, and 2) for the palliative treatment of patients with MM for whom oral therapy is not appropriate. This is the first product to be FDA approved for the high-dose conditioning indication in MM. Spectrum plans to launch EVOMELA with its existing sales force.

“We extend congratulations to our partner Spectrum Pharmaceuticals on achieving FDA approval for EVOMELA in these two indications and look forward to the commercial launch of this product,” said John Higgins, Chief Executive Officer of Ligand. “Through partnerships such as this one, Ligand is able to share in the economic success of important, innovative new drugs across a range of indications and patient populations.”

Spectrum Pharmaceuticals licensed global development and commercialization rights to EVOMELA from Ligand Pharmaceuticals in March 2013. Spectrum assumed responsibility for completing the pivotal Phase II clinical trial, and was responsible for filing the New Drug Application (NDA). Under the license agreement, Ligand received an upfront fee and earned a $6-million milestone payment on EVOMELA approval, as well as royalties on net sales.

Multiple myeloma is a systemic malignancy of plasma cells that accumulate in the bone marrow, usually associated with monoclonal antibody secretion, and results in bone marrow failure and bone destruction. It is the second most common hematologic disease with nearly 30,000 new cases projected in the US in 2016 and more than 11,000 deaths annually (American Cancer Society Stats, 2016). The rate of ASCT for patients with MM is growing by approximately 3.3% annually. Melphalan is the most commonly used IV agent for high-dose conditioning for patients undergoing ASCT for MM. The current IV melphalan market is approximately $100 million annually, with predominant use in ASCT; EVOMELA is the only intravenous melphalan product that is approved for use in the high-dose conditioning indication.

EVOMELA was approved by the FDA based on its bioequivalence to the standard melphalan formulation (Alkeran) in a Phase II clinical study (Aljitawi et al., Bone Marrow Transplant, 2014) via the 505(b)(2) regulatory pathway. EVOMELA has been granted Orphan Drug Designation by the FDA for its use as a high-dose conditioning regimen for patients with MM undergoing ASCT.

EVOMELA’s new melphalan formulation does not contain propylene glycol. The use of the Captisol^® technology to reformulate also contributes to the 4-hour admixture stability of EVOMELA at room temperature. This is in addition to the 1-hour stability of reconstituted EVOMELA drug product at room temperature and 24-hour stability at stability at refrigerated temperature (5°C). Please see the Important Safety Information below and the full prescribing information, including BOXED WARNINGS, for EVOMELA at www.evomela.com.

Ligand Pharmaceuticals Incorporated also recently announced that partner Lundbeck received US FDA approval for Carnexiv™ (carbamazepine) injection as a short-term replacement therapy for oral carbamazepine formulations in adults with certain seizure types when oral administration is temporarily not feasible. Carnexiv received orphan drug designation for this indication and will be the first available intravenous (IV) formulation of the antiepileptic drug (AED) carbamazepine. Lundbeck plans to make Carnexiv commercially available in the US in early 2017. With the approval, Ligand has earned a $1.25-million milestone payment. Ligand is also entitled to receive a royalty of 2.75% on net sales of Carnexiv.

Carnexiv is a short-term (≤7 days) intravenous replacement therapy for oral carbamazepine formulations that provides continuity of care for adult patients who are unable to take carbamazepine by mouth and have the following seizure types:

-Partial seizures with complex symptomatology

-Generalized tonic-clonic seizures

-Mixed seizure patterns which include the above, or other partial or generalized

seizures

As with the oral carbamazepine formulation, there is a risk of serious dermatologic reactions during treatment with Carnexiv, including toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS), as well as a risk of aplastic anemia and agranulocytosis. Partial seizures and generalized tonic-clonic seizures can often be difficult to control.¹ As a result, many patients with epilepsy are on a daily regimen of one or more AEDs that has been carefully adjusted to obtain a therapeutic response. Switching or an abrupt discontinuation of AEDs can lead to seizure recurrence or breakthrough seizures.^2,3

Researchers at the University of Minnesota College of Pharmacy helped conduct early clinical proof-of-concept studies, which were instrumental in developing the formulation of Carnexiv, making intravenous administration possible. James Cloyd, PharmD, Angela Birnbaum, PhD and Ilo E. Leppik, MD at the University of Minnesota partnered closely with Lundbeck during the clinical trial and approval process for Carnexiv.

Ligand’s previous outlook for third quarter 2016 revenue was approximately one-third of the projected total revenues for the second half of 2016 of $66 million to $70 million. The Carnexiv approval milestone had been anticipated for the third quarter and now will be recognized in the fourth quarter.

Carnexiv is an intravenous antiepileptic drug developed in the US by Lundbeck and approved for use in the US. Carnexiv is a short-term (≤7 days) replacement therapy for oral carbamazepine for patients who are unable to take medication by mouth. When switching from oral carbamazepine, the total daily dosage of Carnexiv should be 70% of the total daily dose of oral carbamazepine, divided equally into four separate 30-minute infusions separated by 6 hours. At the end of the intravenous replacement period, patients should be switched back to their previous oral carbamazepine total daily dose and frequency as soon as clinically appropriate.

Please see the full Prescribing Information, including Boxed Warning for serious dermatologic reactions and aplastic anemia and agranulocytosis, for complete details; or go to www.CARNEXIV-US.com for more information.

Sources

1. Mattson R, Cramer J, et al. A comparison of valproate with carbamazepine for the treatment of complex partial seizures and secondarily generalized tonic-clonic seizures in adults. N Engl J Med. 1992. 327(11):765-71.

2. Finamore JM, Sperling MR, et al. Seizure outcome after switching antiepileptic drugs: A matched, prospective study. Epilepsia. 2016 57(8):1294-300.

3. Wang SP, Mintzer ST, et al. Seizure recurrence and remission after switching antiepileptic drugs. Epilepsia 2013. 54:187-193

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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 8 FDA-approved products, including Amgen’s Kyprolis^®, Baxter International’s Nexterone^®, Spectrum Pharmaceuticals’ EVOMELA™, and Merck’s NOXAFIL IV. There are more than 30 Captisol-enabled products currently in clinical development. For more information, visit www.captisol.com.

About Ligand Pharmaceuticals

Ligand is a biopharmaceutical company focused on developing or acquiring technologies that help pharmaceutical companies discover and develop medicines. Our business model creates value for stockholders by providing a diversified portfolio of biotech and pharmaceutical product revenue streams that are supported by an efficient and low corporate cost structure. Our goal is to offer investors an opportunity to participate in the promise of the biotech industry in a profitable, diversified and lower-risk business than a typical biotech company. Our business model is based on doing what we do best: drug discovery, early-stage drug development, product reformulation and partnering. We partner with other pharmaceutical companies to leverage what they do best (late-stage development, regulatory management and commercialization) to ultimately generate our revenue. Ligand’s Captisol^® platform technology is a patent-protected, chemically modified cyclodextrin with a structure designed to optimize the solubility and stability of drugs. OmniAb^® is a patent-protected transgenic animal platform used in the discovery of fully human mono- and bispecific therapeutic antibodies. Ligand has established multiple alliances, licenses and other business relationships with the world’s leading pharmaceutical companies including Novartis, Amgen, Merck, Pfizer, Celgene, Gilead, Janssen, Baxter International and Eli Lilly. Follow Ligand on Twitter @Ligand_LGND.