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pharmafile | October 18, 2007 | News story | Research and Development |Â Â Â
Advaxis cancer vaccine shows encouraging results
Biotechnology company Advaxis has announced positive results from a Phase I/II first-in-man trial of a live listeria vaccine, Lovaxin C, intended to treat patients with cancers that result from human papilloma virus, including cervical cancer and head and neck cancer.
In the safety study, Advaxis reported treatment of 15 patients in three dosage groups with 30 minute 250ml infusions of Lovaxin C at 3-week intervals. Patients were observed for a total of 111 days. All patients had either advanced, recurrent, or progressive cervical cancer, and with the exception of 2 women, all patients were stage IVb (end stage).
Every patient experienced a flu-like syndrome in the 3-12 hours after dosing comprised of fever, chills, nausea, and occasional vomiting, which is consistent with immune stimulation. In the lower 2 doses, symptoms were well tolerated and resolved with the use of over the counter analgesics and antihistamines.
The end point of the study, safety, was met as the assessments confirmed that Lovaxin C was safe to administer intravenously, that the pattern of adverse responses observed, as previously stated above, were consistent with immune stimulation, and that, for this population of patients, a dosage ceiling was determined.
Dr John Rothman, vice president of clinical development in assessing the trial data, said: "Our long held belief that live Listeria vaccines are safe, even in end stage cancer patients, has been confirmed by this study. We have just entered the age of safe bacterial therapies. This milestone has given us the direction for the continued development of Lovaxin C as well as future therapeutic agents."
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Ariad study outlines design of drug-resistant leukemia drugs
Scientists from Ariad Pharmaceuticals have outlined the high-resolution structure of the protein responsible for one of the major clinically relevant genetic variants of drug-resistant chronic myeloid leukemia. Their findings were used to guide the company's design of oral multi-targeted kinase inhibitor, for use in chronic myeloid leukemia and other cancers.
Through X-ray crystallographic studies, Ariad says its study shows in detail how inhibitors of the Bcr-Abl protein, such as AP24534, are able to overcome the structural changes induced by the T315I mutation and bind to the mutated form of the protein.
The data also explains why the first-generation Bcr-Abl inhibitor, imatinib, and second-generation Bcr-Abl inhibitors, such as dasatinib and nilotinib, are not able to inhibit this key genetic variant and thus are not effective against all forms of chronic myeloid leukemia (CML).
In contrast to these first and second generation Bcr-Abl inhibitors, AP24534 potently blocks all clinically relevant forms of the Bcr-Abl protein, including the unmutated protein (the target of imatinib), the commonly mutated proteins (the targets of dasatinib and nilotinib), and the T315I mutated protein.
Tim Clackson, chief scientific officer, said: "There is a growing unmet medical need for new treatment options for CML patients who no longer are responding to first and second generation targeted therapies or have become intolerant to these treatments. This detailed structural analysis of the T315I mutation was a critical step in our effort to design a new targeted therapy for leukemia. These data support our ongoing plans to develop AP24534 in various forms of leukemia and to file an investigational new drug application for AP24534 later this year."
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GlaxoSmithKline and Synta Pharmaceuticals collaborate on skin cancer drug
GlaxoSmithKline and Synta Pharmaceuticals have executed a global collaboration agreement for the joint development and commercialization of a first-in-class, small-molecule, oxidative stress inducer which is entering Phase III clinical development for the treatment of metastatic melanoma.
Under the terms of the agreement, the companies will share responsibility for development and commercialization of the oxidative stress inducer, STA-4783, in the US. GlaxoSmithKline (GSK) will have responsibility for development and commercialization of STA-4783 outside the US, while Synta will receive an upfront cash payment of $80 million.
Synta and GSK will jointly commercialize STA-4783 in the US with Synta receiving a tiered profit share based on levels of annual net sales. The parties will share development costs outside of the US and Synta will receive double-digit tiered royalties on net sales. Safi Bahcall, president and CEO, Synta, said: "GSK and Synta have a shared vision for the development and commercialization of STA-4783 in a range of potential indications, beginning with metastatic melanoma where a Phase IIb study with STA-4783 in combination with Paclitaxel has shown doubling of progression free survival compared to Paclitaxel alone."
Moncef Slaoui, chairman of R&D, GSK, said: "This agreement further strengthens our late-stage oncology pipeline, which currently includes ten Phase III programs, and also demonstrates our commitment to identifying compounds that have the potential to deliver real benefit to patients."
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MediciNova reports positive Phase II results for asthma
Biopharmaceutical company MediciNova has reported positive results from a Phase IIa clinical study of its novel intravenous product candidate for the treatment of acute severe asthma attack.
The randomized, double-blind, placebo controlled, dose-escalation study achieved statistical significance in its primary endpoint of mean change in FEV1 (forced expiratory volume in 1 second) from baseline at 15 minutes (the end of the infusion) at doses of 10, 16, 30 and 60 micrograms/min of novel intravenous asthma product, MN-221 compared to placebo. There were no clinically significant cardiovascular, electrocardiogram, or vital sign changes, nor were there any other safety concerns observed at any dose tested.
Yuichi Iwaki, president and CEO, said: "We are extremely pleased and encouraged by the Phase IIa clinical study results and believe that MN-221 has the potential to become a new standard of care for status asthmaticus.
"The improvements in FEV1 and favorable cardiac safety findings also suggest that MN-221 could be broadly useful in management of asthma and other obstructive lung diseases such as chronic obstructive pulmonary disease. We look forward to further progressing MN-221 through clinical development."
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Sciele completes enrollment in pivotal study for dyslipidemia treatment
Sciele Pharma has completed enrollment of patients in a Phase III trial using pravastatin and fenofibrate to treat mixed dyslipidemia.
Mixed dyslipidemia is the presence of elevated levels of bad cholesterol, low-density lipoproteins and triglycerides, and low levels of good cholesterol, high-density lipoproteins in the blood.
The Phase III clinical trial is being conducted at approximately 75 sites in the US. This study compares the combination of pravastatin and fenofibrate to pravastatin alone and fenofibrate alone.
Larry Dillaha, executive vice president and chief medical officer, Sciele Pharma, said: "We are excited about completing the patient enrollment of this Phase III trial using the combination of fenofibrate and pravastatin. Pravastatin is a well-recognized statin that has been used worldwide for the treatment of dyslipidemias.
"A growing number of patients suffer from mixed dyslipidemia, and many of these patients are being treated with the combination of a statin and a fenofibrate. We believe this new combination product is an excellent strategic fit for our cardio-metabolic product portfolio."
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