A number of biotechnology companies have reached productdevelopment milestones this month, from filing (or amending)an application with the FDA to initiating clinical trials of a leadcompound to completing patient enrollment in a pivotal PhaseIII trial. Here is an update.
-- Cortech Inc. filed an amendment to its investigational newdrug (IND) application for Bradycor. The Denver company plansto test the drug in patients with multiple trauma, a conditionthat results in an inflammatory response that could lead toorgan dysfunction, organ failure or even patient death.
Because bradykinin is an inflammatory mediator generated inresponse to injury, a bradykinin antagonist such as Bradycorcould positively affect patients with multiple trauma.
Cortech (NASDAQ:CRTQ) is also testing Bradycor in patients withsystemic inflammatory response syndrome with presumedsepsis. In addition, Cortech has filed amendments to the IND toinvestigate Bradycor in patients with head injuries, moderateto severe burns and hantavirus infections.
-- Sphinx Pharmaceuticals Corp. has started Phase I clinicals ofits protein kinase C inhibitor Kynacyte in cancer patients. Thetrial will determine the safety and efficacy of the compoundwhen administered intravenously, either alone or incombination with doxorubicin. The Phase I dose-escalatingtrial, to be conducted at New York's Memorial Sloan-KetteringCancer Center, will enroll 20-30 cancer patients.
Sphinx (NASDAQ:SPHX) of Durham, N.C., said it anticipatesbeginning a second Phase I trial of Kynacyte in combinationwith doxorubicin at the Royal Marsden Hospital in the UnitedKingdom in early 1994.
-- The last patient has been enrolled in a multicenter Phase IIIclinical trial of Matrix Pharmaceutical Inc.'s AccuSite Injectionproduct for treating genital warts. The 390 patients accrued forthe trials are being evaluated for complete and partialtreatment responses to high, localized concentrations of thetherapeutic, which consists of a biodegradable protein matrix,5-fluorouracil and the vasoconstrictor epinephrine. Patients arealso being monitored for an extended period following AccuSiteInjection treatment, the Menlo Park, Calif., company(NASDAQ:MATX) said.
-- Preliminary Phase I/II clinical trial results of Gilead SciencesInc.'s potential HIV therapeutic GS 393 were presented at theFirst National Conference of Human Retroviruses and RelatedInfections in Washington, D.C., in mid-December. The data,presented by Robert Walker of the National Institutes of Healthand Ann Collier of the University of Washington, indicated thatadministration of GS 393 is associated with decreased p24antigenemia and transient increases in CD4 counts in selectedAIDS patients. Both measures are used as surrogate markers ofHIV infection. Gilead of Foster City, Calif., said it will also testlower doses of the nucleotide drug via subcutaneousadministration, as well as test GS 393 in patients who arereceiving AZT.
In addition, researchers at Gilead (NASDAQ:GILD) aredeveloping a prodrug of GS 393 to be administered orally.
-- The ethical review board at London's Southampton Hospitalhas approved Arris Pharmaceutical Corp.'s clinical trial protocolon APC 366 for treating asthma. Arris of South San Francisco,Calif., said it intends to begin the trials in January.
The compound is a small-molecule therapeutic for mast cell-mediated inflammation. It's intended to relieve late-stageinflammation triggered by mast cells hours after exposure toan antigen. Arris (NASDAQ:ARRS) created the compound, acytokine mimetic, through a rational drug-design technologythat relies on artificial intelligence strategies.
-- Anthra Pharmaceuticals Inc., a privately held companybased in Princeton, N.J., has completed a Phase I clinical trial ofits drug candidate AD 32 for treating superficial bladdercancer. The company announced preliminary results of thestudy at the Seventh International Symposium of UrologyUpdate 1993 meeting in Portugal. Phase II trials in superficialbladder cancer are under way.
Anthra's AD 32 is a lipophilic anthracycline analog; thecompany is also investigating its use in treating ovarian cancer.
Sepracor Inc. has filed an investigational new drug (IND)application with the FDA to begin clinical trials of its patenteddrug S-ketoprofen. Sepracor of Marlborough, Mass., intends totest the drug's ability to prevent and treat gingivitis andperiodontal disease. S-ketoprofen is a single-isomer form ofketoprofen, a non-steroidal anti-inflammatory drug developedby Wyeth-Ayerst (a division of American Home Products).
Sepracor (NASDAQ:SEPR) has demonstrated that the compoundcauses anti-inflammatory activity in vitro and in vivo,apparently resulting from the drug's ability to blockarachidonic acid metabolism by inhibiting the synthesis of bothleukotrienes and prostaglandins (which mediate inflammatoryprocesses).
-- The antisense drug that Isis Pharmaceuticals Inc. isdeveloping for treating cytomegalovirus (CMV) retinitis inpatients with AIDS has entered the clinic. The drug, ISIS 2922,is the second antisense drug that Isis of Carlsbad, Calif., hasbrought into clinicals. It prevents the production of a proteinnecessary for CMV to replicate.
Isis (NASDAQ:ISIP) initially will conduct a small Phase I studyto examine the safety of ocular injection of ISIS 2922. This anda subsequent trial will focus on patients who have failed withcurrent therapies and have a CMV retinitis that is progressing.
-- Repligen Corp. has initiated a Phase I clinical trial with itssmall-molecule drug AM285. The study is being conducted inpatients with cancers that have not responded to prior therapyor for which there is no standard therapy.
AM285, which was developed by Repligen's wholly ownedsubsidiary, Amira Inc., has been shown to modulate theactivity of creatine kinase, an enzyme that is involved in theproduction of intracellular energy. The compound has beenshown to inhibit the growth of a variety of tumor cell lines andalso inhibit solid tumor growth in animal models.
Repligen (NASDAQ:RGEN) of Cambridge, Mass., also plans toinitiate additional Phase I trials to evaluate AM285's safetyusing different dosing schedules.
-- The monoclonal antibody-based therapeutic that MedarexInc. has developed for treating acute myeloid leukemia (AML)is now in Phase II clinical trials. Approximately 30 patientswith relapsed AML will be enrolled in the multicenter trial ofthe companyUs (NASDAQ:MEDX) compound MDX-11. Thepatients will undergo a standard chemotherapy regimenfollowed by a dose of MDX-11 in an attempt to eliminate anyresidual leukemic cells. Medarex of Princeton, N.J., designed thetrial to determine the optimal dosage, safety and preliminaryefficacy of MDX-11. "We are targeting minimal residual diseaseand plan to evaluate MDX-11's ability to mobilize the body'simmune system and trigger the killing of leukemic cells," saidKathy Selvaggi, who is supervising the trial at the University ofPittsburgh Medical Center.
-- Jennifer Van Brunt Senior Editor
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