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Progenics Pharmaceuticals Announces Positive Topline Results from Registrational Phase 2b Trial of AZEDRA®

On March 30, 2017 Progenics Pharmaceuticals, Inc. (Nasdaq:PGNX), an oncology company developing innovative medicines and other products for targeting and treating cancer, reported that the Company’s registrational Phase 2b trial of its novel radiotherapeutic candidate, AZEDRA (iobenguane I 131) Injection, has achieved its primary endpoint (Press release, Progenics Pharmaceuticals, MAR 30, 2017, View Source [SID1234518338]). The open-label, multi-center study was conducted under a Special Protocol Assessment (SPA) agreement with the Food and Drug Administration (FDA). The trial was designed to evaluate the efficacy and safety of AZEDRA in patients with malignant and/or recurrent pheochromocytoma or paraganglioma, which are rare neuroendocrine tumors. There are currently no approved therapeutics in the U.S. for the treatment of malignant and/or recurrent pheochromocytoma or paraganglioma. AZEDRA has received Breakthrough Therapy, Orphan Drug and Fast Track designations from the FDA.

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The study met the primary endpoint evaluating the proportion of patients who achieved a 50% or greater reduction of all antihypertensive medication for at least six months. Under the study protocol, the primary endpoint is achieved if the lower limit of the two-sided 95% confidence interval was above 10%.

In the trial, 17 (25%) of the 68 evaluable patients experienced a 50% or greater reduction of all antihypertensive medication for at least 6 months. The lower limit of the 95% confidence interval was 16.15%, thus meeting the primary endpoint. The upper limit of the 95% confidence interval was 36.52%.

Progenics also reported favorable data from a key secondary endpoint, the proportion of patients with overall tumor response as measured by Response Evaluation Criteria In Solid Tumors (RECIST) criteria. In this highly pre-treated patient population, 92.2% of patients who received at least one AZEDRA therapeutic dose achieved partial response or stable disease.

"The positive data from this trial are clinically meaningful and provide compelling evidence for the use of AZEDRA to treat malignant and/or recurrent pheochromocytoma and paraganglioma," said Dr. Daniel Pryma, Associate Professor of Radiology & Radiation Oncology and Chief, Division of Nuclear Medicine & Clinical Molecular Imaging at the Perelman School of Medicine at the University of Pennsylvania, the trial’s lead investigator. "Without any approved therapeutics in the U.S. for these rare and devastating life-threatening tumors, patients face a poor prognosis and few options. The tumor response data, in particular for the patients that received two doses, along with the adverse event profile from this trial, suggest that AZEDRA has the potential to be a true breakthrough in addressing these difficult-to-treat patients."

Phase 2b Trial Topline Results
The Phase 2b open-label trial was designed to evaluate the efficacy and safety of two therapeutic doses of AZEDRA administered three months apart to patients with malignant relapsed/refractory pheochromocytoma or paraganglioma.

Primary Endpoint: Reduction in Antihypertensive Medications
Under the study protocol, the primary endpoint is achieved if the lower limit of the two-sided 95% confidence interval was above 10%. In order to achieve this primary endpoint, a minimum of 12 of the total 68 evaluable patients must have a 50% or greater reduction of all antihypertensive medication for at least 6 months. As shown in the table below, 17 patients responded, giving a lower limit of the 95% confidence interval of 16.15%, thus meeting the primary endpoint.

Responders (%) Lower bound of
Confidence Interval Upper bound of
Confidence Interval
Overall
(n=68) 17 (25%)

16.15

%

36.52

%

Two Doses
(n=50) 16 (32%)

20.70

%

45.87

%

One Dose
(n=18) 1 (5.6%)

0.0

%

27.65

%

Secondary Endpoint: Overall Tumor Response Assessment per RECIST Criteria
Best response over 12 months after first therapeutic dose

Complete
Response Partial
Response Stable Disease

Progressive
Disease Unable to
Evaluate
Overall
(n=64*) 0

%

23.4

%

68.8

%

4.7

%

3.1

%

2 doses
(n=50) 0

%

30.0

%

68.0

%

2.0

%

0

%

1 dose
(n=14) 0

%

0

%

71.4

%

14.3

%

14.3

%

*4 patients did not have follow-up scans

AZEDRA was generally well tolerated. The most common treatment emergent adverse events were nausea, thrombocytopenia, anemia, fatigue, leukopenia, and neutropenia. These events are consistent with those observed in prior AZEDRA studies.

"We intend to move quickly to complete our New Drug Application submission by mid-2017, as these topline results underscore the potential of AZEDRA in this ultra-orphan indication," said Mark Baker, Chief Executive Officer of Progenics. "We are grateful to the patients and investigators who participated in this trial, and are committed to bringing a new treatment option to this rare cancer population."

Progenics plans to present additional data from this trial at a medical meeting in the second half of 2017.

Merrimack Stockholders Approve Sale of ONIVYDE® and Generic Version of DOXIL® to Ipsen for Up to $1.025 Billion

On March 30, 2017 Merrimack Pharmaceuticals, Inc. (NASDAQ: MACK) ("Merrimack") reported that, at its Special Meeting of Stockholders held today, its stockholders voted to approve the asset sale with Ipsen S.A (Press release, Merrimack, MAR 30, 2017, View Source [SID1234518337]).

Merrimack will:
Sell to Ipsen its first commercial product ONIVYDE, including U.S. commercialization rights and its licensing agreement with Shire plc; and

Sell to Ipsen its generic version of doxorubicin hydrochloride (HCI) liposome injection ("generic DOXIL") marketed in the United States as DOXIL and advanced under a development, license and supply agreement with Actavis LLC.

Richard Peters, M.D., Ph.D., Merrimack’s President and Chief Executive Officer, said, "I would like to thank our stockholders for their strong support. This compelling transaction will deliver significant and immediate cash value for stockholders while also providing them with the opportunity to participate in the significant potential upside of Merrimack. We are excited to move forward as a more focused, well-funded research and development company targeting three highly promising clinical stage assets, MM-121, MM-141 and MM-310. We will continue to work closely with Ipsen to complete the transaction and achieve a smooth transition."

Merrimack expects the transaction to be completed in the coming days.

Halozyme Provides Update On SWOG Collaborative Group Clinical Study

On March 30, 2017 Halozyme Therapeutics, Inc. (NASDAQ: HALO) reported it has been informed by SWOG, an independent network of researchers that design and conduct cancer clinical trials, that the SWOG Phase 1b/2 trial evaluating PEGPH20 plus modified FOLFIRINOX chemotherapy versus modified FOLFIRINOX alone in patients with previously untreated metastatic pancreas cancer has been temporarily closed to enrollment (Press release, Halozyme, MAR 30, 2017, View Source [SID1234518336]).

During a planned early futility analysis, the independent Data Monitoring Committee found, based on preliminary data in an all comer population, that the addition of PEGPH20 given every two weeks to modified FOLFIRINOX would be unlikely to demonstrate a statistically significant improvement in the primary endpoint of overall survival compared to modified FOLFIRINOX alone. Halozyme is working with SWOG to verify and analyze the initial data set, including a planned analysis by hyaluronan (HA) level, following completion of retrospective determination of tumor HA levels.

"We see every clinical trial involving PEGPH20 as a possibility to advance the study and understanding of how to treat patients with some of the most difficult cancers," said Dr. Helen Torley, president and CEO. "We will work with SWOG to better understand these data and the patients who may best benefit from the addition of PEGPH20."

Halozyme and its collaboration partners have ongoing studies to evaluate PEGPH20 in combination with chemotherapies and immunotherapies in pancreatic, gastric, lung and breast cancers, with plans to initiate additional combination studies in pancreatic, gastric, gall bladder and bile duct cancers later this year.

After Much Anticipation, Cellectar Biosciences Initiates NCI-Supported Phase II Trial of CLR 131 in Multiple Myeloma and Other Blood Cancers

On March 30, 2017 Cellectar Biosciences, Inc. (Nasdaq: CLRB), an oncology-focused clinical stage biotechnology company, reported the initiation of a Phase II clinical study of its lead phospholipid drug conjugate (PDC) CLR 131 in patients with multiple myeloma and other hematologic malignancies (Press release, Cellectar Biosciences, MAR 30, 2017, View Source [SID1234518332]).

The study will be conducted in up to 15 centers in the United States for patients with a variety of orphan-designated relapse or refractory hematologic cancers. The study’s primary endpoint is objective response rate (ORR), with additional endpoints of progression free survival (PFS), median overall survival (OS) and other markers of efficacy following a single 25.0 mCi/m2 dose of CLR 131, with the option for a second 25.0 mCi/m2 dose approximately 75-180 days later. Cellectar will receive approximately $2 million in a non-dilutive grant to help fund the trial from the National Cancer Institute and initial efficacy data are expected as early as the second half of 2017.

"I would like to thank the entire team at Cellectar whose diligent efforts enabled the company to initiate the Phase II trial a full quarter ahead of our original guidance. The prospect of extending patient survival with a one or two-dose treatment continues to drive a high sense of urgency for all involved in this study as we continue to focus on providing clinical benefit to patients who suffer from these difficult to treat conditions," said Jim Caruso, president and CEO of Cellectar Biosciences. "Given the results from our Phase I trial of CLR 131 in multiple myeloma, we are enthusiastic about the potential outcomes of this Phase II trial, and look forward to reporting results as they become available."

The hematologic cancers to be studied include multiple myeloma (MM), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), lymphoplasmacytic lymphoma (LPL), marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), and potentially diffuse large B-cell lymphoma (DLBCL).

In addition to the CLR 131 infusion(s), MM patients will receive 40 mg oral dexamethasone weekly for up to 12 weeks. Efficacy responses will be determined by the latest International Multiple Myeloma Working Group criteria. Efficacy for all lymphoma patients will be determined according to Lugano criteria. More information about the trial, including eligibility requirements, can be found at www.clinicaltrials.gov, reference NCT02952508.

About CLR 131
CLR 131 is an investigational compound under development for a range of hematologic malignancies. It is currently being evaluated as a single-dose treatment in a Phase I clinical trial in patients with relapse or refractory (R/R) multiple myeloma as well as in a Phase II clinical trial for R/R MM and select R/R lymphomas with either a one- or two-dose treatment. Based upon preclinical and interim Phase I study data, treatment with CLR 131 provides a novel approach to treating hematological diseases and may provide patients with therapeutic benefits, including overall survival, an improvement in progression-free survival, surrogate efficacy marker response rate, and overall quality of life. CLR 131 utilizes the company’s patented PDC tumor targeting delivery platform to deliver a cytotoxic radioisotope, iodine-131, directly to tumor cells. The FDA has granted Cellectar an orphan drug designation for CLR 131 in the treatment of multiple myeloma.

About Phospholipid Drug Conjugates (PDCs)
Cellectar’s product candidates are built upon its patented cancer cell-targeting delivery and retention platform of optimized phospholipid ether-drug conjugates (PDCs). The company deliberately designed its phospholipid ether (PLE) carrier platform to be coupled with a variety of payloads to facilitate both therapeutic and diagnostic applications. The basis for selective tumor targeting of our PDC compounds lies in the differences between the plasma membranes of cancer cells compared to those of normal cells. Cancer cell membranes are highly enriched in lipid rafts, which are glycolipoprotein microdomains of the plasma membrane of cells that contain high concentrations of cholesterol and sphingolipids, and serve to organize cell surface and intracellular signaling molecules. PDCs have been tested in more than 80 different xenograft models of cancer.

Bristol-Myers Squibb Enters Collaboration to Leverage Foundation Medicine’s Molecular Information Platform to Identify Predictive Biomarkers Across Multiple Tumor Types and Immunotherapy Agents

On March 30, 2017 Bristol-Myers Squibb Company (NYSE:BMY) and Foundation Medicine (NASDAQ:FMI) reported a collaboration that leverages Foundation Medicine’s comprehensive genomic profiling and molecular information solutions to identify predictive biomarkers such as Tumor Mutational Burden (TMB) and Microsatellite Instability (MSI) in patients enrolled across clinical trials investigating Bristol-Myers Squibb’s cancer immunotherapies (Press release, Bristol-Myers Squibb, MAR 30, 2017, View Source [SID1234518330]). Biomarkers can be used to characterize a tumor and the tumor microenvironment, which may reveal immune-related mechanisms predictive of how a patient may respond to immunotherapy.

Cancer immunotherapy works by helping the immune system mount an anti-cancer response, a process that depends in part on the recognition of cancer-specific proteins called neoantigens. Higher levels of tumor mutations have been shown to correlate to the number of neoantigens, and therefore may help identify patients more likely to respond to cancer immunotherapies. Foundation Medicine’s approach utilizing its FoundationOne assay combines comprehensive genomic profiling with its advanced and proprietary algorithms to measure biomarkers, including TMB and MSI, without the need for whole exome sequencing.

"Translational medicine research is critical to further our understanding of cancer biology and to identify which patient populations are most likely to derive benefit from our Immuno-Oncology agents," said Fouad Namouni, M.D., head of Development, Oncology, Bristol-Myers Squibb. "We believe this collaboration with Foundation Medicine will help us better understand the relation of genomic approaches to immunotherapy efficacy across a number of different tumor types and immunotherapy agents."

"Cancer immuno-therapy is evolving rapidly, and biopharmaceutical companies and practicing oncologists alike may benefit from a reliable, validated, comprehensive view of mutational burden and genomic alterations to make the most informed care decisions," said Melanie Nallicheri, chief business officer and head, Biopharma for Foundation Medicine. "Our collaboration with Bristol-Myers Squibb highlights the potential value of our molecular information platform to the biopharma industry for its ability to inform, to reduce risk and to accelerate clinical development in this high growth and highly competitive oncology field."