Merrimack Pharmaceuticals, Inc announced that it has reached an agreement with Sanofi to regain worldwide rights to develop and commercialise MM-121, a monoclonal antibody designed to block ErbB3 (HER3) activation in patients with heregulin-positive tumours and improve response to standard of care treatments.
In partnership with Sanofi, Merrimack completed an extensive Phase 2 programme 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 tumours 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) Annual Meeting. To view the clinical posters presented at ASCO 2014.
“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 capitalise on our leadership position among the other oncology companies that are pursuing ErbB3,” said Robert Mulroy, President and chief executive officer 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 tumour 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 programme 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 randomised (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 per cent of the pretreatment biopsies suggests a link between heregulin levels and pCR rates.
For the TNBC cohort, rates for serious adverse events were 28.1per cent vs. 15.6 per cent and rates for grade 3 or higher adverse events were 50.0 per cent vs. 31.3 per cent 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 55.2per cent on treatment arm versus 53.1per cent on control arm.
MM-121 is a fully human monoclonal antibody that targets ErbB3, a cell surface receptor that is activated by the ligand heregulin. Heregulin-driven ErbB3 signaling has been implicated as a mechanism of tumour growth and resistance to targeted, cytotoxic and anti-endocrine therapies. When used in the combination setting, MM-121 is designed to block ErbB3 signaling in order to restore or enhance the anti-tumour effect of a combination therapy partner.
MM-121 has been investigated in four Phase 2 and six Phase 1 clinical studies covering a broad spectrum of patient populations and drug combinations. An extensive translational component of the MM-121 clinical programme was designed to establish clinically useful biomarkers that were initially identified using Merrimack’s systems biology approach and confirmed in preclinical studies.
Vials of breast cancer drug Herceptin, thought to have been stolen in Italy, and falsified, tampered and re-introduced into the EU supply chain, according to the European Medicines Agency (EMA).
This is currently being investigated by Member State authorities and updates will be provided as more information becomes available. Italian law enforcement authorities are currently investigating the theft and are looking at whether other medicines may also be affected. At present, no affected product has so far been identified at hospital level and there are no reports that any harm has come to patients in relation to the falsified medicine and authorities are working to avoid this.
Healthcare professionals across the EU are being alerted to the falsified Herceptin vials and are being provided with information on signs seen so far that may indicate a vial is not genuine. These include: the batch numbers and expiry dates on most vials do not match those on the outer package; there is liquid present in some vials of Herceptin powder for solution (Herceptin is a white to yellow powder); evidence of tampering with the rubber stoppers, crimping caps or lids; the falsified vials are labelled as Italian Herceptin 150 mg.
This is based on the information available at present. If healthcare professionals notice anything else that looks suspicious in relation to Herceptin vials they should alert their national competent authority. Falsified medicines must not be used. Appropriate measures to protect public health are being taken by Member States.
The numbers of the Herceptin batches known to be affected are H4311B07, H4329B01, H4284B04, H4319B02, H4324B03, H4196B01, H4271B01, H4301B09 and H4303B01.
Although only a small number of vials is thought to be affected, the marketing authorization holder for Herceptin, as a precautionary measure, is recalling vials suspected of having being falsified. In addition, parallel distributors across the EU are being alerted with the above information.
The EMA is coordinating the response by the appropriate health authorities in the Member States. Although all information is not yet available, it is not expected that this will result in shortage of medicines for cancer patients. The EMA is monitoring the situation closely and will provide updates as appropriate.
Dr. L H Hiranandani Hospital and International Oncology Services organized ‘The Pink Meet – 2014’, a comprehensive conference to discuss new medical insights on breast cancer, in Mumbai on February 1 and 2 in which over 150 doctors from across the country assembled to share their latest experiences and knowledge for breast cancer care and treatment.
The social impact of breast cancer was also discussed in this two-day comprehensive breast cancer care conference with topics such as “Fertility beyond breast cancer.” Niranjan Hiranandani, Chief Managing Trustee of Dr. L H Hiranandani Hospital inaugurated the conference.
Leading cancer specialists including Dr. Rajendra Badwe, Dr. Suresh Advani, Dr. Rajiv Sarin, IVF specialist, Dr. Anirudhha Malpani and nuclear medicine expert Dr. Vikram Lele shared their insights and experiences on the new practices in diagnoses, treatment and care for breast cancer including genetics of the disease, breast reconstruction post treatment, role of nuclear medicine in early diagnosis, etc.
Oncology experts from Dr. L H Hiranandani Hospital, including Dr. Namita Pandey, Dr. Prasad Raj Dandekar and Dr. Wasim Phoplunkar were also present at the event this year.
Dr. Sujit Chatterjee, CEO, Dr. L H Hiranandani hospital and also the Chief coordinator of ‘The Pink Meet – 2014’ stated, “Realizing the need for medical community’s engagement in the fight against breast cancer, Dr. L H Hiranandani Hospital along with International Oncology started ‘The Pink Meet’: a medical conference with social relevance. The conference today has moved beyond deliberating the scientific aspects of breast cancer and also discusses the social impact; such as issues of fertility after cancer treatment. We are proud to provide the experts in the field a platform yet again to interact with the fraternity and discuss their experiences.”
The coordinator for the event, Dr. Neeraj Mehta, & Regional Head – International Oncology Services Pvt. Ltd., said, “With ‘The Pink Meet,’ we are trying to provide tremendous support and hope and information to help the patients (women). On such a wide platform doctors can come and share knowledge about the medical advances made in the field of breast oncology and their experiences. This would help them render the best possible treatment to their patients.”
Source : PharmaBiz
AVEO Oncology and Astellas Pharma Inc. have jointly decided to discontinue the BATON (Biomarker Assessment of Tivozanib in ONcology) breast cancer clinical trial, a phase II study in patients with locally recurrent or metastatic triple negative breast cancer (TNBC), due to insufficient enrollment. AVEO previously announced that enrollment in this study had been slower than anticipated, and enrollment rates did not improve substantially following additional patient recruitment efforts.
“While we believe in the potential benefits of tivozanib for patients with triple negative breast cancer, we have decided to discontinue the trial because of low patient accrual,” stated William Slichenmyer, MD, Sc.M., chief medical officer at AVEO. “We want to thank the study investigators and their patients who participated in the trial for their support.”
The BATON-BC study initiated patient enrollment in December 2012 in a randomized, double-blind, multicenter phase II clinical trial, evaluating the efficacy of tivozanib in combination with paclitaxel compared to placebo in combination with paclitaxel in patients with locally recurrent or metastatic triple negative breast cancer who have received no more than one systemic therapy for advanced or metastatic breast cancer. All committed expenses related to the BATON-BC study are shared equally between AVEO and Astellas.
Separately, as announced in December 2013, data from a planned interim analysis of the phase II study of tivozanib in patients with colorectal cancer indicate that the study is unlikely to meet the primary endpoint in the intent-to-treat patient population. Interim data are being evaluated, and AVEO and Astellas are in discussions regarding next steps.
AVEO Oncology is a cancer therapeutics company committed to discovering and developing targeted therapies designed to provide substantial impact in patients’ lives by addressing unmet medical needs.
Source : PharamaBiz