Companies seek game-changer for CKD

ABBOTT PARK, Ill.—Abbott Laboratories has agreed to payReata Pharmaceuticals Inc. $450 million in upfront and near-term cash paymentsin exchange for the exclusive rights to develop and commercialize Reata'spivotal-stage chronic kidney disease (CKD) candidate, bardoxolone methyl,worldwide, excluding the U.S. and certain Asian markets.

Under the agreement, announced Sept. 23, Irving, Texas-basedbiotech firm Reata will retain exclusive rights to bardoxolone in the UnitedStates, the largest CKD market in the world. Reata is also eligible formilestones totaling $350 million, plus sales royalties.

If successful, bardoxolone methyl could be considered theelixir for 20 million Americans diagnosed with moderate to serious CKD, alife-threatening illness expected to increase alongside the rising numbers ofobesity cases forecast over the next four decades. Half of CKD patients alsohave diabetes, the leading cause of CKD, with as many as 30 to 40 percent oftype 2 diabetics developing the disease.

The market for CKD therapeutics is $13billion annually, and is expected to grow to $20 billion by 2016.

Reata partnered on bardoxolone with Kirin last December for$272 million plus royalties for marketing rights in certain Asian markets.Bardoxolone is an oral antioxidant inflammation modulator (AIM) that activatesthe transcription factor Nrf2, which Reata says leads ultimately to a decreasein the level of oxidative stress and suppresses a number of inflammatorymediators. The potentially life-changing drug is currently in late Phase IItrials for the treatment of CKD.

The partnership "allows us to meet our strategic goal ofestablishing our own commercial presence in the U.S. and building asustainable, fully integrated pharmaceutical company," says Reata CEO WarrenHuff.

Current available therapies slow the progression of CKD, butpatients ultimately progress to dialysis. Not only have clinical studies shownearly promise, but this is the first time a drug has shown this level ofsustained improvement in CKD patients, Huff says.

"We've been working on this for years," Huff tells ddn. "When we had compelling clinical data, Abbott wasinterested in the partnership—especially offshore."

Abbott, for its part, now adds to its pipeline a late-stagedrug for diabetes-associated kidney disease. Bardoxolone has the potential tocover Abbot's bill, which can increase to as much as $900 million, healthcareexperts estimate. The deal also gives Abbott rights to certain other Reatacompounds for CKD, cardiovascular and metabolic indications in the sameterritories.

Tracy L. Sorrentino, a spokeswoman for Abbott, tells ddn that the partnership "provides Abbott with alate-stage clinical asset, consistent with our strategy to augment ourpharmaceutical pipeline with external compounds and expertise."

"Reata has a very promising compound that has the potentialto be the first the first disease-modifying treatment option for CKD, whileAbbott brings decades of expertise in renal care, plus clinical development andregulatory expertise—particularly outside the U.S.—and we have a commercialpresence in renal with Zemplar," Sorrentino says.

Abbott claims the Reata drug represents a promising newaddition to its late-stage pipeline and will build on its existing expertise inrenal care. Phase II studies with the drug in patients with stage 3b and 4 CKSand type 2 diabetes have shown that treatment results in statisticallysignificant increases in estimated glomerular filtration rate and improvementsin other key markers of renal function, the company reports.

"Early clinical studies suggest that bardoxolone could be asignificant improvement to the current standard of care for chronic kidneydisease and possibly prevent patients from progressing to the later stages ofthe disease and dialysis," says Dr. John Leonard, senior vice president ofpharmaceuticals R&D at Abbott.

Both companies will work together on the clinicaldevelopment plan, including regulatory filings, while commercialization costswill be covered by the territory owner. Reata is responsible for fundingR&D expenses.

"It's too soon to say what the commercial potential mightbe, but we feel sales could be significant, given the patient need and the datawe have seen in the clinical trials," Sorrentino says.