NEW YORK _ Genetics Institute Inc. Wednesdaylaunched Phase III trials of recombinant interleukin-11(IL-11) for platelet restoration in cancer chemotherapypatients.
The Cambridge, Mass.-based company also said the FDArecently granted approval for resumption of clinicalstudies involving recombinant interleukin-12 (IL-12).Phase II trials of the cytokine IL-12 _ a cytotoxic drugfor advanced kidney cancer _ were halted last summerafter patients experienced adverse reactions to the drug.As many as 12 patients were hospitalized and one died.
Tuan Ha-Ngoc, Genetics Institute's executive vicepresident, said the IL-12 development program willcontinue with Phase I/II studies for HIV and cancer.
In speaking to investors at Oppenheimer & Co.'s SixthAnnual Health Care Conference, Ha-Ngoc said results ofthe company's investigation of the discontinued Phase IItrials will be released Sunday at a meeting of the NewYork Academy of Sciences.
Although details of the findings were not discussedWednesday, Genetics Institute spokesman Dennis Harpdescribed the problem as "unprecedented" in drugdevelopment, adding that it involved "the dose and thetiming of dose administration."
The Phase III trials of IL-11 will involve 250 cancerchemotherapy patients at 40 medical centers. The patientswill receive either 50 micrograms per kilogram of IL-11or a placebo. The studies will test whether the drugreduces reliance on platelet transfusions, which is thestandard treatment for restoring platelets destroyed bychemotherapy.
All patients also will receive Neupogen, which is madeby Thousand Oaks, Calif.-based Amgen Inc., to boostwhite blood cells if they become neutropenic.
Data released in May 1995 from Phase II trials of IL-11showed the drug achieved statistical significance inreducing the overall number of platelet transfusions.Given in doses of 50 micrograms per kilogram, IL-11eliminated the need for transfusions in 30 percent of thetreated patients. All but 4 percent of the patients in theplacebo group required transfusions.
Reduction in platelets, which are involved in bloodclotting, can lead to excessive bleeding. IL-11 is an anti-inflammatory cytokine that stimulates production both ofmegakaryocytes, the precursors of platelets, and earlierstem cells.
Ha-Ngoc said the trials, with full patient accrual, areexpected to be complete in 12 to 18 months. An analysiswill be conducted about mid-way through the studies andif the results demonstrate success, Genetics Institutecould file for FDA approval based on the interim data.
Among the competitors for Genetics Institute in plateletrestoration are Amgen and Genentech Inc., of South SanFrancisco. Both Amgen and Genentech are evaluatingversions of thrombopoietin (TPO) in early clinical trials.
TPO, Harp said, is an end-stage differentiation factorinvolved in transforming megakaryocytes into platelets.IL-11, on the other hand, acts earlier in blood celldevelopment so that even if all megakaryocytes are killedby the chemotherapy, the drug still is expected tostimulate platelets.
In addition, Genetics Institute plans to evaluate IL-11 as atreatment for chemotherapy induced mucositis in PhaseI/II trials slated to begin by the end of this year. And thedrug is being tested in Phase II studies to restore bloodcells in combination with bone marrow and peripheralstem cell transplants.
Genetics Institute intends to market IL-11 in NorthAmerica. The company partnered with Schering-PloughCorp., of Madison, N.J., to market IL-11 in Europe andwith Yamanouchi Pharmaceutical Co. Ltd., of Tokyo, tosell the drug in Japan.
In other Asian countries, IL-11 will be marketed byGenetics Institute's majority shareholder, AmericanHome Products Inc., of Madison, N.J., which owns 63percent.
Last week, American Home Products moved to take overanother biotechnology company in which it holds amajority position. The pharmaceutical company, whichowns 54.6 percent of Immunex Corp., has offered $263million to buy-out the Seattle-based firm, which alsodevelops blood cell stimulating drugs.
Ha-Ngoc said he is not aware of any impact on GeneticsInstitute from American Home Products' acquisition ofImmunex. American Home products has an option topurchase the rest of Genetics Institute based on a pricethat escalates from a current $73.95 per share to $85 pershare in December 1996, when the option expires.
Genetics Institute's stock (NASDAQ:GENIZ) closeddown 50 cents Wednesday to $41.25 per share.
By the time IL-11 is ready for the market, GeneticsInstitute expects to use a sales force that already will be inplace for recombinant Factor IX, another blood-relatedproduct. Recombinant Factor IX is a clotting drug beingtested in Phase III trials for hemophilia B. Ha-Ngoc saidGenetics Institute plans to file an application for FDAapproval next year.
If approved, Factor IX would be the first GeneticsInstitute product marketed by the company. GeneticsInstitute's recombinant Factor VIII is sold worldwide byBaxter Healthcare Inc., of Deerfield, Ill., for hemophiliaA, the most common form of the disease. n
-- Charles Craig
(c) 1997 American Health Consultants. All rights reserved.