Cangene closed on a potentially $300-plus million purchase of worldwide rights to IB1001, a recombinant factor IX (rFIX) for treatment and prevention of bleeding in patients with hemophilia B, and two preclinical drug candidates from the bankrupt Inspiration Biopharmaceuticals and its lead investor, French-owned Ipsen, the sellers said today.
As part of the deal, Cangene acquired commercialization rights from Inspiration and Ipsen to IB1001, now under review by U.S. and European regulators, as well as Inspiration’s rights to drug candidates IB1007 (recombinant FVIIa) and IB1008 (recombinant FVIII). Cangene agreed to pay Inspiration and Ipsen $5.9 million up-front, plus up to $50 million sales milestones totaling $50 million and annual net sales payments tiered up to a double-digit percentage of global net sales.
The deal is the second by Inspiration and Ipsen in as many months. On Jan. 24, the U.S. Bankruptcy Court in Boston approved Baxter International’s planned acquisition from the sellers of worldwide rights to OBI-1, a recombinant porcine factor VIII (rpFVIII) for congenital hemophilia A with inhibitors against human FVIII and acquired hemophilia A.
Baxter agreed to pay $50 million up-front, up to $135 million tied to undisclosed development and commercial milestones, as well as tiered net sales payments ranging from 12.5% to 17.5% of OBI-1 annual net sales. The Baxter deal is under review by the U.S. Federal Trade Commission under the Hart-Scott-Rodino Act. The total value of the Baxter deal for OBI-1 may exceed $700 million, Inspiration and Ipsen disclosed today in their statement on the Cangene deal.
OBI-1 and IB1001 were both lead candidates of Inspiration, which filed for Chapter 11 protection from creditors in October, nearly four months after the FDA placed two late-stage clinical trials for IB1001 under clinical hold. The clinical hold impacts a Phase III study of IB1001 in previously treated pediatric subjects with hemophilia B, designed to measure the drug candidate’s pharmacokinetics, safety, and efficacy over 50 exposure days; and a Phase II/Phase III IB1001 study whose primary endpoint is degree of hemorrhage control by treatment regimen.
According to Inspiration, FDA “recently” sent Inspiration a Complete Response Letter detailing why the company’s Biologics License Application for IB1001 cannot be approved in its current form. The company said the letter is consistent with previous discussions with FDA on the presence of host cell proteins (HCP) in IB1001 that were responsible for formation of anti-HCP antibodies in 26% of clinical trial subjects. In the statement, Inspiration said it implemented manufacturing process changes designed to “significantly” reduce HCP levels.
“Preliminary comparability data available to date on drug substance manufactured using the original and the modified processes suggest that the process changes have been successful with no observed deleterious effect on the factor IX protein itself,” Inspiration and Ipsen said in their statement.
With no additional clinical data requested by FDA, next steps for developing IB1001 will be determined by Cangene. In a separate statement, Cangene said the development program for the drug candidate included “a comprehensive set of pharmacokinetic, safety, and efficacy data from Phase [III] clinical trials in people affected by hemophilia B, including a surgery sub-study.”
In Europe, IB1001 is under regulatory review by the European Medicines Agency (EMA), which is studying a Marketing Authorization Application submitted by Cangene in August 2011.
"We will use our significant experience in developing and commercializing biological products to respond to the additional regulatory requirements as we seek to address a significant global need for hemophilia B patients," John A. Sedor, Cangene’s president and CEO, said in the company statement.
Cangene specializes in developing, manufacturing, and commercializing plasma-derived products for multiple therapeutic areas that include infectious disease, and related areas of hematology and transplantation.
The clinical hold froze action on a Phase III trial evaluating IB1001’s safety and efficacy in treating and preventing bleeding episodes in adults with hemophilia B, as well as a Phase III/IIIb study evaluating IB1001’s safety and efficacy to treat and prevent bleeding episodes in previously treated children with hemophilia B.
The hold came after Inspiration reported to the FDA that, during the course of routine laboratory evaluations, it found that a higher-than-expected proportion of individuals treated with IB1001 had developed antibodies to proteins from the Chinese hamster ovary, or CHO, host cells used to manufacture the therapy. At the time, a total of 86 people with hemophilia B had received IB1001 in clinical studies, with no adverse events related to the development of antibodies to CHO protein reported to that time.