Author: [email protected]

Vernalis and Servier achieve Research Milestone as BCL-2 inhibitor drug candidate enters Phase I

On June 19, 2014 Vernalis and Servier reported the achievement of a milestone following the treatment of the first patient in a Servier sponsored Phase I trial with a promising new drug candidate, a selectiveBCL-2 inhibitor identified through their joint oncology drug discovery collaboration (Press release, Servier, JUN 19, 2014, View Source [SID:1234508825]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

This BCL-2 selective inhibitor is the first drug candidate stemming from an on-going collaboration between Vernalis and Servier aimed at discovering anticancer drug candidates selective for individual BCL-2 family members.

Ian Garland, CEO of Vernalis commented: "We are delighted that this new BCL-2 inhibitor candidate has now entered Phase I trials and look forward to further success from our broad, strategic collaboration with Servier."

Jean-Pierre Abastado, Director of the Center of Therapeutic Innovation in Oncology at Servier, said: "Our experience with Vernalis shows that small molecules tailored against specific targets can have very high therapeutic potential. This success was achieved through a comprehensive chemistry and biology research program with our teams identifying and characterizing this promising BCL-2 inhibitor. This new compound further extends Servier’s portfolio beyond kinase inhibitors, HDAC inhibitors and immunotherapeutic products."

About BCL-2 target:

Proteins of the BCL-2 family are crucial regulators of apoptosis. Deregulations of this protein family play a major role in the aberrant survival of tumour cells. Within this protein family, BCL-2 belongs to the pro-survival members and is often overexpressed in tumour cells. Pro-survival BCL-2 family members have been recognized as attractive therapeutic targets in oncology for more than twenty years but drug discovery research on this class of target is particularly challenging and requires innovative chemistry supported by structural biology.

Merrimack Pharmaceuticals to Regain Worldwide Rights to Develop and Commercialize MM-121

On June 19, 2014 Merrimack Pharmaceuticals reported that it has reached an agreement with Sanofi to regain worldwide rights to develop and commercialize MM-121, a monoclonal antibody designed to block ErbB3 (HER3) activation in patients with heregulin-positive tumors and improve response to standard of care treatments (Press release Merrimack, JUN 19, 2014, View Source [SID:1234500596]).

In partnership with Sanofi, Merrimack completed an extensive Phase 2 program for MM-121 which was designed to assess the role of ErbB3 in a number of cancer indications in both the metastatic and neoadjuvant settings. In advanced settings of ovarian cancer, ER/PR+ HER2 negative breast cancer and non-small cell lung cancer, Merrimack was able to identify that heregulin, the principal ligand that binds to and activates the ErbB3 receptor, is associated with poor response to standard of care therapy and that adding MM-121 may restore sensitivity in these most at-risk patients. Consistent across three metastatic cancer indications with three different standard of care therapies, patients in these trials with heregulin-positive tumors experienced a statistically significant reduction in their risk of progression when they received a combination with MM-121. Heregulin-driven drug resistance pathways were found to be active in approximately 30-50 percent of patients tested. Data from these studies were recently presented at the 2014 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

“We are grateful for Sanofi’s support over the last five years and believe that the data generated through this partnership validate the potential for MM-121 to help patients most at risk for progression on current therapies. Regaining MM-121 is an opportunity to capitalize on our leadership position among the other oncology companies that are pursuing ErbB3,” said Robert Mulroy, President and CEO at Merrimack. “With these data and the feedback we’ve received from our committed investigators, we believe MM-121 has the potential to be a foundational therapy for use across multiple solid tumor types and we plan to continue its development through subsequent strategic partnerships. Our next step is to discuss our Phase 2 data and potential registration paths with the FDA.”

Sanofi will continue to fund the existing MM-121 Phase 2 program for the next six months. The neoadjuvant cohort of a Phase 2 study testing MM-121 in combination with paclitaxel in patients with triple negative breast cancer is the final study to be completed through this collaboration. Top line results of that study are below.

Results from the Second Cohort of a Phase 2 Study of MM-121 in Combination with Paclitaxel in Neoadjuvant Breast Cancer

Merrimack and Sanofi completed a randomized (2:1), exploratory Phase 2 study testing MM-121 in combination with paclitaxel followed by doxorubicin and cyclophosphamide. The study was conducted in two populations of patients with either ER/PR positive (ER/PR+) HER2 negative breast cancer (n=101) or triple negative breast cancer (TNBC) (n=99). There was no formal quantitative endpoint specified for this study.

In November 2013, Merrimack released initial top line results from the ER/PR+ HER2 negative cohort. Those results demonstrated that patients who received the combination of MM-121 and paclitaxel achieved a pCR rate of 10.6% (95% CI [5.2; 20.3]) compared to 3.3% (95% CI [0.6; 16.7]) for the control arm. Top line results from this second cohort of patients with TNBC showed that patients who received the combination of MM-121 and paclitaxel achieved a pCR rate of 42.9% (95% CI 30.8; 55.9) compared to 51.7 (95% CI 34.4; 68.6) for the control arm. Translational analysis is ongoing for both cohorts and the full data set will be reported at a future medical conference. Preliminary analysis of approximately 50 percent of the pretreatment biopsies suggests a link between heregulin levels and pCR rates.

For the TNBC cohort, rates for serious adverse events were 28.1% vs. 15.6%, and rates for grade 3 or higher adverse events were 50.0% vs. 31.3% between the treatment and control arms, respectively. As reported previously, in the ER/PR+ HER2 negative cohort, similar frequencies were reported for adverse events of any grade between the treatment and control arms, with no unexpected toxicities experienced and no increase in serious adverse events. Grade 3 or worse adverse events in the ER/PR+ HER2 negative cohort were 55.2% on treatment arm versus 53.1% on control arm.

Johnson & Johnson Innovation Catalyzes New and Exciting Science and Technology in Pharmaceutical, Medical Device, Diagnostic and Consumer Healthcare Spaces

On June 19, 2014 Johnson & Johnson Innovation, LLC reported that Janssen Biotech, Inc. and Johnson & Johnson Innovation have formed a research collaboration with Weill Cornell Medical College aimed at developing compounds for targeting the function of a lymphoma causing protein (Press release Johnson & Johnson, JUN 19, 2014, View Source [SID:1234500594]). Through the collaboration, investigators at Weill Cornell and Janssen drug development researchers will collaborate to discover, validate and characterize inhibitors of the protein and further elucidate novel targeting methods.

Takeda Announces Termination of Orteronel (TAK-700) Development for Prostate Cancer in Japan, U.S.A. and Europe

On June 19, 2014 Takeda reported that it has voluntarily decided to end the development program for orteronel (TAK-700) for prostate cancer (Press release Takeda, JUN 19, 2014, View Source [SID:1234500592]). The decision follows the results of two Phase 3 clinical trials in metastatic, castration resistant prostate cancer (mCRPC). The studies found while orteronel plus prednisone could extend the time patients lived before their cancer progressed, it did not extend overall survival in these patients. After careful consideration of the data from these trials, the company has determined that the drug has not demonstrated a clinical profile sufficient to move forward in mCRPC, given the availability of other therapies.

On May 14, 2014, Takeda announced results from ELM-PC4, a pivotal, international, double blind, randomized Phase 3 trial in men with mCRPC who had not received chemotherapy, which showed that orteronel plus prednisone improved radiographic progression free survival (rPFS) compared to prednisone alone, one of the study’s two primary endpoints, but did not show a statistically significant improvement in the study’s second primary endpoint of overall survival (OS). A previously reported Phase 3 trial, ELM-PC5, in men with mCRPC that had progressed during or following chemotherapy, was unblinded in 2013 after a pre-specified interim analysis indicated that orteronel plus prednisone would likely not meet the primary endpoint of improved overall survival when compared to the control arm. The interim analysis did show an advantage for orteronel plus prednisone for the secondary endpoint, radiographic progression-free survival over the control arm. There were no significant safety concerns in either study.

Takeda is in communication with trial investigators and the relevant regulatory authorities, to provide them with updated and current information in compliance with local regulations. Takeda is working with trial investigators and local regulatory authorities to ensure that patients who participated in the orteronel (TAK-700) trials are transitioned to appropriate therapies so that trial participants receive appropriate care. Patients enrolled in the orteronel (TAK-700) clinical trials are urged to consult their study investigators to address any questions, and before making any changes to their medication.

Takeda remains committed to oncology and to the treatment of prostate cancer.

Analyst: GlaxoSmithKline’s Tykerb dead in the water after breast cancer failure

GlaxoSmithKline’s ($GSK) cancer treatment Tykerb took a blow last month when it failed a major late-stage trial in breast cancer. Now, at least one analyst figures the drug is crippled by that data–and that marketing it for breast cancer would be a waste of money (FierceBiotech, Analyst: GlaxoSmithKline’s Tykerb dead in the water after breast cancer failure, JUN 17, 2014, View Source [SID:1234510055]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The study that torpedoed Tykerb compared Roche’s Herceptin–the gold standard in HER2-positive breast cancer–against the combination of Herceptin and the GSK drug in patients who had undergone surgery. Obviously, the hope was that adding Tykerb to Herceptin would be a boost for those patients. But it wasn’t; the dual therapy failed to show statistical superiority over Herceptin alone at staving off the disease.

Based on response data from another study, hopes were high for Tykerb in post-surgery patients. Now, with the new trial failure on the one hand–and Roche’s new line-up of HER2-positive cancer therapies, Perjeta and Kadcyla, on the other–Tykerb’s chances look slim, GlobalData analyst Jamie Mallinson figures.

Adding to the uncertainty about Tykerb’s future is the fact that it will go to Novartis as part of Glaxo’s oncology portfolio sale to the Swiss drugmaker in a $16 billion deal. "Tykerb has failed to establish itself as a strong competitor in the HER2-positive market, and its use in the adjuvant setting was the only way it could gain a decent share of the breast cancer therapeutics market after Roche launched Perjeta and Kadcyla," Mallinson said in a recent report.

Coming on top of last year’s Tykerb failure in HER2-positive gastric cancer, the loss in breast cancer is a big disappointment. The upshot? GlobalData figures there is "little more to expect" from the drug. So, the firm says, neither Glaxo nor Novartis is likely to expend much effort–or money–marketing Tykerb.

But after Novartis inked its deal for the GSK cancer portfolio in April, analysts said that the Swiss drugmaker could easily add Tykerb to its marketing lineup. Sales reps working on the Novartis treatment Afinitor, which is approved for breast cancer as well as other forms of the disease, could also tout Tykerb with little additional effort or expense. Whether Novartis can prove the Tykerb naysayers wrong? We’ll have some time to wait and see.