title: MSI-78 Magainin Pharmaceuticals.
abstract: Magainin is developing MSI-78, a 22-amino acid peptide, based on compounds discovered in frog skin, as a topical anti-infective. It has broad-spectrum activity, covering Gram-positive and -negative bacteria, anaerobic bacteria and Candida albicans. The compound also has potential for the treatment of impetigo and healing wounds with various infections. In July 1998, Magainin filed an NDA with the US FDA for the treatment of infections in diabetic foot ulcers [292671]. It expects to launch the drug during the second quarter of 1999 [275844]. A completed pivotal, 584 patient, phase III trial demonstrated statistical equivalence between MSI-78 and orally-administered ofloxacin, for the treatment of infection in diabetic foot ulcers. MSI-78 was comparable to ofloxacin with respect to the primary endpoint of clinical response of infection at day ten of treatment, and at subsequent time points through to day 28, and at follow-up [220339]. These data were confirmed by the company's second phase III trial for the same indication, for which successful results were announced in March 1997 [239274]. Additional data from this second trial, presented at the 37th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), demonstrated that both drugs were comparable in terms of eradication rate of individual organisms and wound healing [264410]. Between 10% and 15% of wounds in patients treated with a combination of both drugs reached closure within four weeks. After six weeks, the closure rate increased to between 18% and 30%. This suggested that additional studies should be performed to evaluate the wound-healing effects further [275279]. The side-effects of both treatments were well-tolerated, although treatment with ofloxacin was associated with a significant excess of insomnia compared to MSI-78 [275844]. Further phase III trials are planned for treatment of surgical wounds, decubitus ulcers, venous stasis ulcers and infections associated with burns [173293]. The primary clinical endpoint is the cure of the infection and the secondary endpoint is the eradication of the organism. The first study has enrolled approximately 400 patients [195065]. The drug was also being developed for impetigo, but proved no better than placebo in phase III trials for the treatmentprimarily because 75% of controls showed clinical improvement as a result of better hygiene [293751]. Magainin is attempting to develop a recombinant process for commercial synthesis of MSI-78 to allow it to compete on price with conventional antibiotics [174944], [176153]. Magainin has a contract with Abbott for the manufacture of the drug [174944]. In February 1997, Magainin entered into a development, supply and distribution agreement in North America with SmithKline Beecham (SB) for Cytolex [234035]. Magainin has retained all rights to the drug outside of North America [275844], although it has also signed an agreement with Ambalal Sarabhai Enterprises (ASE) to commercialize MSI-78 (as Cytolex) in India [274544], [275556]. Analysts estimate the potential revenues of this compound, including off-label usage is between $200 and $250 million in the US and up to half as much again outside the US [191231].
authors.affiliation: Hoechst Marion Roussel, 102 Route de Noisy, 93235 Romainville Cedex, France. Khalid.Islam@hmrag.com
authors.forename: K
authors.initials: K
authors.lastname: Islam
authors.forename: S P
authors.initials: SP
authors.lastname: Hawser