Round-up of clinical trial debutantes
other drugs for other infectious diseases feature strongly in
DrugResearcher's periodic round-up of new compounds entering the
clinic.
Switzerland's Basilea Pharmaceutica, a spin out of Roche, has presented initial clinical data on ceftobiprole, the first of a new class of broad-spectrum cephalosporin antibiotics that was specially designed to bind the mutated targets in methiciillin resistant Staphylococcus aureus with potent bactericidal activity towards both MRSA and penicillin-resistant Streptococcus pneumoniae. The data confirm that ceftobiprole is a potent anti-MRSA drug for patients with complicated skin and skin structure infections
Meanwhile, Basilea has also reported progress with BAL8557, a novel water-soluble azole suitable for both oral and intravenous administration for mucocutaneous and invasive fungal infections. The drug has now completed Phase I clinical development and is anticipated to start Phase II this year.
Microbia has started a Phase I clinical trial of MD-1100, a novel orally administered compound under investigation for the treatment of irritable bowel syndrome (IBS). MD-1100 is a potent superagonist of guanylate cyclase-C, a receptor found on the surface of intestinal cells. Preclinical studies show that MD-1100 acts on the key defining attributes of IBS, increasing gastrointestinal transit and secretion while decreasing gastrointestinal pain. The primary objectives of the Phase I studies are to evaluate the safety, pharmacokinetic, and pharmacodynamic properties of MD-1100 in healthy volunteers.
FibroGen has started human trials of FG-2216, an investigational therapy for anaemia that unlike current injectable therapies based on erythropoietin can be given orally. Initial results suggest the drug is safe and well tolerated and significantly increases production of endogenous EPO in healthy human subjects. FG-2216 given orally two or three times weekly and increased the number of circulating reticulocytes (young red blood cells) compared with placebo over the course of administration. It acts as an inhibitor of hypoxia-inducible factor-prolyl hydroxylase (HIF-PH).
Curagen will start a Phase I trial of CR002, a fully human monoclonal antibody that targets PDGF (platelet-derived growth factor)-D, which is being developed as a potential treatment for patients with IgA nephropathy, next month. PDGF-D is a mediator known to stimulate mesangial cell proliferation, which is believed to be an underlying cause in the progression of disease toward kidney failure. It is believed that patients with diabetes, lupus, and IgA nephropathies have chronic mesangial cell proliferation caused by excess PDGF-D that could be neutralised by CR002. The trial should be completed in the second half of 2005.
Inhibitex has reported positive results from preclinical studies and a Phase I clinical trial of Aurexis, a humanised monoclonal antibody that targets ClfA, a protein located on the surface of virtually all strains of S aureus. It is being developed as a first-line therapy, in combination with standard of care antibiotics for serious, life threatening S aureus infections. Data from preclinical animal studies demonstrated that Aurexis provided significant prophylactic and therapeutic activity against these infections, including those caused by MRSA. The clinical trial in healthy volunteers showed that Aurexis was generally safe and well tolerated. A Phase II study is ongoing.
Neurocrine Biosciences has started a clinical trial of its proprietary compound urocortin-2 in healthy volunteers, with a view to initiating a Phase II study in patients with mild to moderate congestive heart failure early next year. The study is being conducted in two parts: a pilot study which has been completed to refine dosing followed by a Phase I study in a group of healthy subjects. Based on pre-clinical data, Neurocrine believes urocortin-2 has positive hemodynamic effects on cardiac output and blood pressure, effects that may benefit congestive heart failure patients.
Genomics-based drug discovery firm Exelixis has initiated a Phase I clinical trial to evaluate the tolerability and pharmacokinetic profile of XL999, a novel proprietary anticancer compound that targets multiple receptor tyrosine kinases implicated in tumour cell proliferation and angiogenesis.
The phase I clinical trial of compound XL999, which will be administered by intravenous infusion, is a dose-finding safety study in patients with solid tumours for whom no standard treatment is available or current treatments are ineffective. XL999 is the second spectrum selective kinase inhibitor (SSKI) that the company has brought forward in clinical development. Each SSKI has a different spectrum of receptor tyrosine kinases (RTK) inhibition offering the potential to achieve efficacy through inhibition of multiple RTKs based on their established or potential involvement in cancer.
Pharmacyclics has presented interim data from a Phase I clinical trial of Xcytrin (motexafin gadolinium) Injection, the company's lead cancer therapeutic candidate, in combination with Taxotere (docetaxel) for the treatment of patients with advanced refractory tumours. The firm has also announced the initiation of a Phase I trial of Xcytrin in combination with Taxotere and cisplatin for treatment of patients with non-small cell lung cancer (NSCLC). Xcytrin has been shown in laboratory studies to inhibit thioredoxin reductase, a key enzyme in cellular metabolism.
Theratechnologies has started a two-part Phase I clinical trial of ThGLP-1 (TH0318), a glucagon-like peptide-1 (GLP-1) analogue in development as a treatment for diabetes. Plans call for results to be disclosed in the first quarter of 2005. ThGLP-1 is a stabilised analogue of human GLP-1, a endogenous hormone involved in glucose control.
