AMAG Pharmaceuticals, Inc. announced Wednesday that it has entered into an agreement that grants AMAG an exclusive option to acquire the rights to an orphan drug candidate at the conclusion of a Phase 2b/3a clinical trial. Digoxin immune fab is a polyclonal antibody being developed for the treatment of severe preeclampsia in pregnant women. AMAG will make an upfront payment of $10 million from cash on hand to Velo Bio, LLC, a privately held life-sciences company, for the option to acquire global rights to the DIF program. Velo Bio, LLC, is a joint venture between Glenveigh Pharmaceuticals of Chattanooga and QuatroBio.
Preeclampsia is a serious multi-system disorder that presents in the second or third trimester of pregnancy, and is associated with new onset hypertension and in many cases excess protein in the urine and end organ dysfunction that may endanger both the mother and baby. Severe preeclampsia affects approximately 1 percent of pregnancies and is characterized by more difficult-to-control hypertension and the potential for end organ damage that is severe enough
to require immediate delivery of the baby in order to stop disease progression in the mother. It is one of the leading causes of maternal death in the United States and is responsible for approximately 20 percent of premature births in the nation each year.
"Despite the significant health consequences of severe preeclampsia to at-risk mothers and their babies, there are currently no FDA-approved treatment options available for these patients," said Julie Krop, M.D., AMAG's chief medical officer and senior vice president, clinical development and regulatory affairs. "The development and eventual approval of DIF for the treatment of severe preeclampsia could have a significant impact on the lives of these pregnant women and their babies and would nicely complement AMAG's growing portfolio of maternal health products."
Elevated levels of endogenous digitalis-like factor have been found in the placental and maternal circulation of the majority of patients with preeclampsia, and the degree of elevation is correlated with disease severity. DIF is thought to bind to these factors, causing a decrease in serum EDLF levels and inhibition of their activity. A prior placebo-controlled Phase 2 study in 51 pregnant women with severe preeclampsia validated DIF's mechanism of action and was suggestive of clinical benefit in both mothers and their babies. DIF has been granted both orphan drug and fast-track review designations by the U.S. Food and Drug Administration for the use in the treatment of severe preeclampsia. DIF has four issued patents, the longest of which provides protection through 2032.
"AMAG has built a strong maternal health business platform that has the ability to reach many at-risk pregnant women and their physicians, making them an ideal partner for our DIF program," said Stephen Butts, chief executive officer of Velo. "We believe the compound has demonstrated early potential to help address this very serious health complication of pregnancy."
Under the option agreement, Velo will complete a dose ranging study and a Phase 2b/3a clinical study. Following conclusion of the DIF Phase 2b/3a study, AMAG may exercise, extend or terminate the acquisition option. If AMAG exercises its option to acquire DIF, it would pay an option fee and a potential U.S. approval milestone, totaling up to $75 million. AMAG would also be responsible to pay any additional costs in pursuing FDA approval beyond the planned Phase 2b/3a clinical trial, as well as up to $250 million in sales milestone payments and single-digit royalties. The sales milestones are payable at annual product sales starting at $100 million up to $900 million. AMAG anticipates that results from the pivotal Phase 2b/3a study could be available as early as 2018.
"This is another example of our disciplined financial approach – in this case making measured investments at key value inflection points in an important development stage product like DIF, which will serve to expand our maternal health business and aid pregnant women in areas of high unmet need, such as severe preeclampsia," said William Heiden, chief executive officer of AMAG.
Glenveigh, a Chattanooga-based company formed by maternal fetal medicine specialist David Adair, M.D., is focused on developing treatments for complicated pregnancies and is the originator of the DIF program for preeclampsia. QuatroBio, located in Morrisville, N.C., is led by Moise Khayrallah, Ph.D. and Stephen Butts, entrepreneurs with a track record of drug development success. Most recently, Dr. Khayrallah and Mr. Butts founded Aerial BioPharma, where they successfully developed ADX-N05 (now JZP-110), which was acquired by Jazz Pharmaceuticals in 2014. Prior to Aerial, they founded Neuronex, acquired by Acorda in 2012, and Addrenex, acquired by Shionogi in 2009.