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Studies Show bioTheranostics’ Breast Cancer Index Identifies Breast Cancer Patients at Risk for Early and Late Recurrence, and Predicts Benefit from Extended Endocrine Therapy

bioTheranostics, developer of innovative molecular diagnostics, reported results from two new studies evaluating the performance of its Breast Cancer Index (BCI) biomarker assay in estrogen-receptor positive (ER+), early stage breast cancer. Study results showed that BCI predicts which women with early stage ER+ breast cancer are at risk for early and late distant recurrence, and which are most likely to benefit from continuing treatment with endocrine therapy after completing five years of tamoxifen.

BCI is a combinatorial biomarker with a novel mechanism of action composed of Molecular Grade Index (MGI) and the two-gene expression ratio HOXB13/IL17BR (H/I).

In a study published online in the Journal of the National Cancer Institute, tumor samples from 83 patients with breast cancer recurrence were matched to 166 patients without disease recurrence from the MA.17 trial, a landmark randomized clinical study that demonstrated improved disease-free survival with extended letrozole therapy in postmenopausal patients with ER+ breast cancer who were recurrence-free following an initial five years of tamoxifen therapy. In patients receiving extended endocrine therapy, a high H/I gene expression ratio, as measured by the BCI assay, remained significantly associated with benefit from extended endocrine therapy (p=0.0061), representing a 16.5 percent reduction in the risk of recurrence with extended letrozole treatment compared with placebo. Patients with low H/I did not benefit from extended letrozole treatment. The study authors concluded that the BCI assay identifies a subgroup of breast cancer patients disease-free after five years of tamoxifen therapy who are at risk for late recurrence, and that high H/I predicts benefit from extended endocrine therapy. The study was conducted by researchers from leading institutions, including Massachusetts General Hospital.

A second study, published online in the journal Clinical Cancer Research, examined the ability of the BCI test to predict early (0-5 years) and late (>5 years) distant recurrence in ER+, lymph node-negative breast cancer patients. The study was a retrospective analysis of tumor samples from tamoxifen-treated patients from the randomized, prospective Stockholm trial (n=317) and a multi-institutional cohort from two academic medical centers (n=358). Within the Stockholm trial cohort, BCI stratified the majority (~65 percent) of patients as low risk, with <3 percent distant recurrence rate for 0-5 years and 5-10 years. In the multi-institutional cohort, which had larger tumors, 55 percent of patients were classified by BCI as low risk, with a <5 percent distant recurrence rate for 0-5 and 5-10 years. For both groups, the BCI assay was the most significant prognostic factor beyond standard clinicopathological factors for 0-5 and >5 years. The authors concluded that the ability of the BCI test to assess risk of both early and late distant recurrence has clinical utility for decisions of chemotherapy at diagnosis and for decisions about extended endocrine therapy beyond five years.

Richard Ding, president and CEO of bioTheranostics, said there is a growing need for novel biomarkers in ER+ early stage breast cancer that guide disease management beyond the initial 5-year window. “Breast Cancer Index is the only biomarker test that has been shown in prospective trials to predict the benefit of extended endocrine therapy,” Ding said. “The results of these key studies illustrate the importance of the BCI test in identifying which patients are at risk for early and late breast cancer recurrence, and who among them will benefit from extended endocrine therapy, which is of significant clinical value. This critical information should allow many women to avoid unnecessary treatment and for the clinical focus to be on those in most need of therapy.”

Study: Prediction of Late Disease Recurrence and Extended Adjuvant Letrozole Benefit by the HOXB13/IL17BR Biomarker

Study: Breast Cancer Index Identifies Early-Stage Estrogen Receptor–Positive Breast Cancer Patients at Risk for Early- and Late-Distant Recurrence

Source: Business Wire

The Medicines Company and Alnylam Form Strategic Alliance to Develop and Commercialize RNAi Therapeutics Targeting PCSK9 for the Treatment of Hypercholesterolemia

The Medicines Company (Nasdaq: MDCO) and Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, recently announced that they have formed an exclusive global alliance for the development and commercialization of Alnylam’s ALN-PCS RNAi therapeutic program for the treatment of hypercholesterolemia.

“This new alliance unites two organizations with a shared culture and commitment to innovation. In my view and past experience, there could be no stronger partner for our ALN-PCS program than The Medicines Company, which has demonstrated industry-wide leadership in the advancement of cardiovascular medicines to patients and remarkable success in its strategy of in-licensing, developing, and commercializing breakthrough products,” said John Maraganore, Ph.D., Chief Executive Officer of Alnylam. “For Alnylam, this new partnership enables the advancement of ALN-PCS, an important program within our ‘Alnylam 5×15’ product development and commercialization strategy focused on RNAi therapeutics directed toward genetically validated targets. We believe that the ALN-PCS program holds great promise for the development of a significant therapeutic option for patients with hypercholesterolemia, and that the unique mechanism of action for ALN-PCS could provide a differentiated and potentially best-in-class strategy for PCSK9 antagonism.”

“Our focus on acute and intensive care medicine has led us to a leadership position with Angiomax® (bivalirudin) and potentially with cangrelor in the management of patients in extreme risk as a consequence of the rupture of their vulnerable coronary artery plaque at and around the time of acute coronary syndromes. Meantime, we have made progress with MDCO-216 (ApoA-1 Milano), a turbocharged form of HDL-C (‘good cholesterol’) which has the potential to modify disease through reverse cholesterol transport,” said Clive Meanwell, M.D., Ph.D., Chairman and Chief Executive Officer of The Medicines Company. “Now, this exciting collaboration with Alnylam – leaders in their field of RNAi – adds a second potentially disease modifying approach and more cutting edge technology to our portfolio. We have seen that PCSK9 gene silencing can substantially reduce LDL-cholesterol in patients and has epidemiological and disease mechanisms studies suggest this can further reduce the risks of the world’s number one killer, coronary artery disease. Clearly we see the complementarity of approaches which increase ‘good cholesterol’ (HDL-C) and decrease ‘bad cholesterol’ (LDL-C). We look forward to working with our colleagues at Alnylam for whom we have the greatest respect and admiration based upon earlier collaborations particularly around Angiomax, which was invented by John Maraganore.”

PCSK9 (proprotein convertase subtilisin/kexin type 9) is a protein that regulates low-density lipoprotein (LDL) receptor levels on hepatocytes; gain-of-function human mutations in PCSK9 are associated with hypercholesterolemia while loss-of-function mutations are associated with lower levels of LDL cholesterol and a reduced risk of cardiovascular disease. ALN-PCS is a PCSK9 synthesis inhibitor that reduces intracellular and extracellular levels of PCSK9 resulting in lowered plasma levels of LDL-C. MDCO-216 is a naturally occurring variant of a protein found in high-density lipoprotein, or HDL. It is a reverse cholesterol transport agent designed to reduce atherosclerotic plaque burden development and thereby reduce the risk of adverse thrombotic events.

Under this alliance, The Medicines Company and Alnylam intend to collaborate on the advancement of the ALN-PCS program. Alnylam’s ALN-PCS program includes ALN-PCS02 – an intravenously administered RNAi therapeutic which has completed a Phase I trial, and ALN-PCSsc – a subcutaneously administered RNAi therapeutic currently in pre-clinical development. Alnylam will continue the program for an estimated one to two years to complete certain pre-clinical and Phase I clinical studies. The Medicines Company is responsible for leading and funding development from Phase II forward and commercializing the ALN-PCS program if successful. Under the terms of the agreement, The Medicines Company will make an upfront cash payment of $25 million to Alnylam. Alnylam may also receive potential development and commercial milestone payments of up to $180 million. Alnylam will be eligible to receive scaled double-digit royalties on global products sales of ALN-PCS products.

Alnylam has completed a Phase I trial of ALN-PCS02 in healthy volunteer subjects with elevated baseline LDL-C. Results showed that administration of a single intravenous dose of drug, in the absence of concomitant lipid-lowering agents such as statins, resulted in statistically significant and durable reductions of PCSK9 plasma levels of up to 84% and lowering of LDL-C of up to 50%. ALN-PCS02 was shown to be generally safe and well tolerated in this study and there were no serious adverse events related to study drug administration. Alnylam has also presented pre-clinical data from its ALN-PCSsc program demonstrating potent knockdown of the PCSK9 target gene with an ED50 of less than 0.3 mg/kg after a single subcutaneous dose.

“Cardiovascular disease remains the leading cause of mortality worldwide, with elevated LDL-C a major modifiable risk factor. New strategies are needed to dramatically and rapidly reduce LDL-C and prevent acute cardiovascular events that result from the rupture of cholesterol rich plaque when patients are at their most vulnerable,” said Daniel J. Rader, M.D., professor of Medicine and chief, Division of Translational Medicine and Human Genetics, at the Perelman School of Medicine at the University of Pennsylvania. “As a key regulator of the LDL receptor, liver-expressed PCSK9 is one of the most important and best validated new targets in molecular medicine for the treatment of hypercholesterolemia. The ALN-PCS data generated to date are very encouraging and I look forward to continued clinical studies that highlight the unique mechanistic approach of PCSK9 synthesis inhibitors.”

Dr. Rader serves as a member of Alnylam’s Scientific Advisory Board and as a consultant on Alnylam’s ALN-PCS program, and Alnylam and Dr. Rader collaborate on research for which Alnylam provides materials.

Source: The Medicines Company

EXINI and Active Biotech Initiate Collaboration, Aiming to Clinically Evaluate the Future of Cancer Treatment

EXINI Diagnostics AB (NASDAQ OMX First North: EXINI) and Active Biotech AB (NASDAQ OMX NORDIC: ACTI) start collaboration within clinical trials. The aim is to use the opportunity offered by EXINI Bone™ to monitor disease progression in advanced prostate cancer, using the BSI (Bone Scan Index) value, a new imaging biomarker. BSI is thought to be useful in studying the effect of tasquinimod in the treatment of patients with castrate-resistant prostate cancer (CRPC).

The Scientist Webinar: Tackling the Challenges Involved with Protein Biomarkers

Protein biomarkers have been hailed as vital stepping stones in the race to personalize medicine. But many hurdles remain to be cleared before their application becomes routine. Currently, protein biomarkers have proven useful in drug discovery and development, as tools for target discovery and evaluation of a drug’s mechanism of action, and in therapies for prevention, early detection, diagnosis, and treatment of disease. Although single markers are in use, more widespread adoption will probably require a multiplexed panel capable of detecting and measuring biomarkers accurately, inexpensively, and easily in biological samples that are highly complex.

Cleveland BioLabs Announces Publication of Studies Identifying Biomarkers of CBLB502’s Efficacy as a Radiation Countermeasure

Cleveland BioLabs, Inc. (Nasdaq:CBLI) recently announced the online publication of studies identifying biomarkers of CBLB502’s efficacy as a radiation countermeasure in the Journal of Pharmacology and Experimental Therapeutics, a leading peer-reviewed research journal in the field of pharmacology. The reported studies were conducted by scientists of Cleveland BioLabs in collaboration with researchers at the Armed Forces Radiobiology Research Institute and the F. Edward Hébert School of Medicine at the Uniformed Services University of the Health Sciences, and Roswell Park Cancer Institute.