On December 7, 2016 Abbott (NYSE: ABT) reported it has filed a complaint to terminate its proposed acquisition of Alere based on the substantial loss in Alere’s value following the merger agreement (Press release, Abbott, DEC 7, 2016, View Source [SID1234517000]).

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In the 10 months following the Jan. 30, 2016, signing of the agreement, Alere has suffered a series of damaging business developments, including the government eliminating the billing privileges of a substantial Alere division, the permanent recall of an important product platform, multiple new government subpoenas, including two new criminal subpoenas, and a five-month delay in filing its 10K coupled with admissions of internal control failures requiring restatement of its 2013-2015 financials.

"Alere is no longer the company Abbott agreed to buy 10 months ago," said Scott Stoffel, divisional vice president of external communications, Abbott. "These numerous negative developments are unprecedented and are not isolated incidents brought on by chance. We have attempted to secure details and information to assess these issues for months, and Alere has blocked every attempt. This damage to Alere’s business can only be the result of a systemic failure of internal controls, which combined with the lack of transparency, led us to filing this complaint."

Under terms of the merger agreement, Abbott may terminate the transaction if adverse events materially change Alere’s long-term prospects. Abbott filed its complaint seeking termination in the Delaware Court of Chancery, citing these events among others as material adverse events.

On December 7, 2016 Panther Biotechnology, Inc. reported that it has received positive feedback from the submission presented to the U.S. Food and Drug Administration ("FDA") pursuant to a Pre-IND (Investigational New Drug) meeting with the Division of Oncology Products 1 (DOP1) of the Center for Drug Evaluation and Research (CDER) of the FDA (Press release, Panther Biotechnology, DEC 7, 2016, View Source [SID1234517402]). The purpose of the requested meeting was to obtain FDA’s input regarding Panther’s plans for the development of TRF-DOX, Panther’s novel transferrin-doxorubicin conjugate initially planned for the treatment of platinum-resistant ovarian cancer. In preparation for the meeting, Panther submitted a Pre-IND Package to FDA that described the information Panther intends on submitting in the TRF-DOX IND submission planned in 2017. The IND is the regulatory vehicle that will allow for the initiation of clinical trials with TRF-DOX initially for the treatment of ovarian cancer.

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Panther submitted the request to seek guidance on a Phase 2a Open Label Sequential Cohort, Ascending Dose, Blinded, DOXIL controlled Study to Evaluate the Safety, Pharmacokinetics and Preliminary Efficacy of Multiple Doses of TRF-DOX Administered Intravenously every 4 weeks for up to 12 months to patients with Advanced Platinum-refractory or -resistant Ovarian Cancer. The primary objective will be to evaluate the safety and tolerability of TRF-DOX administered intravenously to subjects with advanced platinum-refractory or resistant ovarian cancer for up to 12 months. Secondary objectives are tumor response rate (complete and partial responses) assessed every 3 months for 12 months following treatment according to Response Evaluation Criteria in Solid Tumors version 1.1. (RESIST) criteria, progression-free survival at 6 and 12 months following first injection of TRF-DOX and overall survival at 6 and 12 months following first injection of TRF-DOX.

FDA reviewed Panther’s manufacturing, preclinical pharmacology and toxicology, and clinical plans for TRF-DOX and provided specific feedback. In general, FDA agreed with Panther’s plans and offered further recommendations and comments. The manufacturing and nonclinical pharmacology and toxicology plans with TRF-DOX were deemed adequate pending review of actual data by FDA in the IND.

In addition, FDA had input into the design of the Phase 2b clinical trial with TRF-DOX which will be considered in the protocol submitted with the IND.

"This is a significant leap for Panther as we prepare to enter clinical trials in the US and we look forward to getting started," stated Evan Levine, Chief Executive Officer of Panther. "We are extremely pleased and thankful for not only the valuable feedback we received from FDA but also from the productive recommendations to manage TRF-DOX through the next stage of clinical development. Based on earlier encouraging clinical results, we believe we may have a greater opportunity for increasing clinical benefit for patients receiving treatment."
TRF-DOX binds to transferrin receptors on tumor cells, inhibits cancer cell proliferation and causes cell death. TRF-DOX has been shown to exhibit increased cytotoxicity relative to unconjugated doxorubicin toward a variety of cancer cell lines and reduced cytotoxicity to normal cells. In addition to improvements in cytotoxicity and selectivity, TRF-DOX exhibits cytotoxic effects in many multidrug-resistant cells in vitro. Tumor targeting of doxorubicin to transferrin receptors on the cell membranes of tumor cells is intended to improve the therapeutic index of doxorubicin and to reduce the development of doxorubicin resistance.

On December 7, 2016 Merck (NYSE:MRK), known as MSD outside the United States and Canada, reported positive health-related quality of life (HRQoL) findings from an exploratory analysis from the phase 3 KEYNOTE-024 study investigating the use of KEYTRUDA (pembrolizumab), the company’s anti-PD-1 therapy, compared to standard of care (SOC) platinum-containing chemotherapy for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express high levels of PD-L1 (tumor proportion score [TPS] of 50 percent or more) (Press release, Merck & Co, DEC 7, 2016, View Source [SID1234516980]). Specifically, patient-reported outcomes showed clinically meaningful improvement with KEYTRUDA compared to chemotherapy. Findings will be presented today at the 17th World Conference on Lung Cancer (WCLC) hosted by the International Association for the Study of Lung Cancer.

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"The patient-reported quality of life outcomes we are seeing in the KEYNOTE-024 study are very encouraging and, coupled with previously reported clinical data from this study, including a survival benefit, are important in understanding the robust clinical profile for KEYTRUDA compared to chemotherapy," said Dr. Roger Dansey, senior vice president and therapeutic area head, oncology late-stage development, Merck Research Laboratories.

Dr. Julie Brahmer of the Johns Hopkins Kimmel Cancer Center will present these findings as part of a plenary session at WCLC in Vienna, Austria at 8:45 a.m. CET (Abstract #PL04a.01).

"For people living with lung cancer, who often face serious health challenges brought on by the disease, quality of life is a major concern when determining treatment and the data presented today help us further understand the potential clinical benefit for KEYTRUDA in these patients," said Dr. Martin Reck, head of the thoracic oncology department, LungenClinic Grosshansdorf, Germany.

The KEYTRUDA (pembrolizumab) clinical development program includes more than 30 tumor types in nearly 400 clinical trials, including more than 200 trials that combine KEYTRUDA with other cancer treatments. Merck has an expansive research program in NSCLC and is currently advancing multiple registration-enabling studies with KEYTRUDA as monotherapy and in combination with other treatments.

Findings from KEYNOTE-024

KEYNOTE-024 is a randomized, open-label, phase 3 study investigating KEYTRUDA monotherapy compared to SOC platinum-containing chemotherapy for the first-line treatment of patients with metastatic NSCLC. The study enrolled 305 patients who had not received prior systemic chemotherapy for their metastatic disease and whose tumors had high PD-L1 expression (TPS of 50 percent or more) with no EGFR or ALK aberrations. Patients were randomized to receive a 200 mg fixed dose of KEYTRUDA every three weeks (n=154) or four to six cycles of investigator’s choice platinum-based chemotherapy (n=151). The primary outcome measure was progression-free survival. Key secondary outcomes were overall survival, overall response rate and safety; exploratory outcomes were duration of response and patient-reported outcomes.

The HRQoL data presented at WCLC were based on change from baseline to week 15 as assessed by two European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaires measuring global health status (such as physical, emotional, cognitive, and social functioning as well as fatigue and pain) (QLQ-C30) and time to deterioration (measuring symptoms such as cough, chest pain, alopecia, and dyspnea) (QLQ-LC13). Across treatment arms, patient-reported outcome compliance was greater than 90 percent at baseline and approximately 80 percent at week 15.

The findings showed that HRQoL and symptoms were improved or maintained to a greater degree with KEYTRUDA compared to chemotherapy (based on 299 patients who completed at least one questionnaire). Specifically, the improvement in global health status from baseline to week 15 (difference in least squares) for KEYTRUDA was 6.9 (95% CI, 3.3-10.6) compared to -0.9 (95% CI, -4.8-3.0) in the chemotherapy arm. Analysis based on specific functioning and symptoms showed more patients treated with KEYTRUDA (pembrolizumab) reporting an improvement in global health status and/or quality of life, fatigue, and pain compared to patients treated with chemotherapy. Fewer patients in the KEYTRUDA arm experienced deterioration compared to chemotherapy (30.5% and 39.2%, respectively), with a prolonged time to deterioration also observed in the KEYTRUDA arm (hazard ratio: 0.66 [95% CI, 0.44-0.97; p=0.029]).

About KEYTRUDA (pembrolizumab)

KEYTRUDA is a humanized monoclonal antibody that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

KEYTRUDA is administered as an intravenous infusion over 30 minutes every three weeks for the approved indications. KEYTRUDA for injection is supplied in a 100 mg single use vial.

KEYTRUDA Indications and Dosing

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma at a dose of 2 mg/kg every three weeks until disease progression or unacceptable toxicity.

Lung Cancer

KEYTRUDA is indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have high PD-L1 expression [tumor proportion score (TPS) ≥50%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA is also indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.

In metastatic NSCLC, KEYTRUDA (pembrolizumab) is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.

Head and Neck Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. In HNSCC, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.

Selected Important Safety Information for KEYTRUDA (pembrolizumab)

KEYTRUDA can cause immune-mediated pneumonitis, including fatal cases. Pneumonitis occurred in 94 (3.4%) of 2799 patients receiving KEYTRUDA, including Grade 1 (0.8%), 2 (1.3%), 3 (0.9%), 4 (0.3%), and 5 (0.1%) pneumonitis, and occurred more frequently in patients with a history of prior thoracic radiation (6.9%) compared to those without (2.9%). Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 or recurrent Grade 2 pneumonitis.

KEYTRUDA can cause immune-mediated colitis. Colitis occurred in 48 (1.7%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.4%), 3 (1.1%), and 4 (<0.1%) colitis. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4 colitis.

KEYTRUDA can cause immune-mediated hepatitis. Hepatitis occurred in 19 (0.7%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.4%), and 4 (<0.1%) hepatitis. Monitor patients for changes in liver function. Administer corticosteroids for Grade 2 or greater hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA.

KEYTRUDA can cause hypophysitis. Hypophysitis occurred in 17 (0.6%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.2%), 3 (0.3%), and 4 (<0.1%) hypophysitis. Monitor patients for signs and symptoms of hypophysitis (including hypopituitarism and adrenal insufficiency). Administer corticosteroids and hormone replacement as clinically indicated. Withhold KEYTRUDA (pembrolizumab) for Grade 2; withhold or discontinue for Grade 3 or 4 hypophysitis.

KEYTRUDA can cause thyroid disorders, including hyperthyroidism, hypothyroidism, and thyroiditis. Hyperthyroidism occurred in 96 (3.4%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.8%) and 3 (0.1%) hyperthyroidism. Hypothyroidism occurred in 237 (8.5%) of 2799 patients receiving KEYTRUDA, including Grade 2 (6.2%) and 3 (0.1%) hypothyroidism. Thyroiditis occurred in 16 (0.6%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.3%) thyroiditis. Monitor patients for changes in thyroid function (at the start of treatment, periodically during treatment, and as indicated based on clinical evaluation) and for clinical signs and symptoms of thyroid disorders. Administer replacement hormones for hypothyroidism and manage hyperthyroidism with thionamides and beta-blockers as appropriate. Withhold or discontinue KEYTRUDA for Grade 3 or 4 hyperthyroidism.

KEYTRUDA can cause type 1 diabetes mellitus, including diabetic ketoacidosis, which have been reported in 6 (0.2%) of 2799 patients. Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Administer insulin for type 1 diabetes, and withhold KEYTRUDA and administer antihyperglycemics in patients with severe hyperglycemia.

KEYTRUDA can cause immune-mediated nephritis. Nephritis occurred in 9 (0.3%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.1%), and 4 (<0.1%) nephritis. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 nephritis

KEYTRUDA can cause other clinically important immune-mediated adverse reactions. For suspected immune-mediated adverse reactions, ensure adequate evaluation to confirm etiology or exclude other causes. Based on the severity of the adverse reaction, withhold KEYTRUDA and administer corticosteroids. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Based on limited data from clinical studies in patients whose immune-related adverse reactions could not be controlled with corticosteroid use, administration of other systemic immunosuppressants can be considered. Resume KEYTRUDA when the adverse reaction remains at Grade 1 or less following corticosteroid taper. Permanently discontinue KEYTRUDA (pembrolizumab) for any Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction.

The following clinically significant immune-mediated adverse reactions occurred in less than 1% (unless otherwise indicated) of 2799 patients: arthritis (1.5%), exfoliative dermatitis, bullous pemphigoid, rash (1.4%), uveitis, myositis, Guillain-Barré syndrome, myasthenia gravis, vasculitis, pancreatitis, hemolytic anemia, and partial seizures arising in a patient with inflammatory foci in brain parenchyma.

KEYTRUDA can cause severe or life-threatening infusion-related reactions, which have been reported in 6 (0.2%) of 2799 patients. Monitor patients for signs and symptoms of infusion-related reactions, including rigors, chills, wheezing, pruritus, flushing, rash, hypotension, hypoxemia, and fever. For Grade 3 or 4 reactions, stop infusion and permanently discontinue KEYTRUDA.

Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. If used during pregnancy, or if the patient becomes pregnant during treatment, apprise the patient of the potential hazard to a fetus. Advise females of reproductive potential to use highly effective contraception during treatment and for 4 months after the last dose of KEYTRUDA.

KEYTRUDA was discontinued due to adverse reactions in 8% of 682 patients with metastatic NSCLC. The most common adverse event resulting in permanent discontinuation of KEYTRUDA was pneumonitis (1.8%). Adverse reactions leading to interruption of KEYTRUDA occurred in 23% of patients; the most common (≥1%) were diarrhea (1%), fatigue (1.3%), pneumonia (1%), liver enzyme elevation (1.2%), decreased appetite (1.3%), and pneumonitis (1%). The most common adverse reactions (occurring in at least 20% of patients and at a higher incidence than with docetaxel) were decreased appetite (25% vs 23%), dyspnea (23% vs 20%), and nausea (20% vs 18%).

It is not known whether KEYTRUDA is excreted in human milk. Because many drugs are excreted in human milk, instruct women to discontinue nursing during treatment with KEYTRUDA and for 4 months after the final dose.

Safety and effectiveness of KEYTRUDA have not been established in pediatric patients.

Our Focus on Cancer

Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck, helping people fight cancer is our passion and supporting accessibility to our cancer medicines is our commitment. Our focus is on pursuing research in immuno-oncology and we are accelerating every step in the journey – from lab to clinic – to potentially bring new hope to people with cancer.

As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the fastest-growing development programs in the industry. We are currently executing an expansive research program that includes nearly 400 clinical trials evaluating our anti-PD-1 therapy across more than 30 tumor types. We also continue to strengthen our immuno-oncology portfolio through strategic acquisitions and are prioritizing the development of several promising immunotherapeutic candidates with the potential to improve the treatment of advanced cancers.

For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.

On December 7, 2016 ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA), a rare cancer-focused innovative biotechnology company, reported clinical data on brigatinib, its investigational anaplastic lymphoma kinase (ALK) inhibitor, from the pivotal ALTA trial in ALK-positive (ALK+) non-small cell lung cancer (NSCLC) patients who had experienced disease progression on crizotinib therapy (Press release, Ariad, DEC 7, 2016, View Source;p=RssLanding&cat=news&id=2228143 [SID1234516982]). As of May 31, 2016, the data show that of patients on the 180-mg regimen with a median follow-up of 11 months, 55 percent achieved confirmed objective response as assessed by the investigator. In this arm, the median progression-free survival (PFS) was 15.6 months in this post-crizotinib setting, by both investigator and independent review committee (IRC) assessment. Additionally, in this arm, 67 percent of patients with measurable brain metastases achieved a confirmed intracranial objective response, and intracranial PFS was 18.4 months among patients with any brain metastases at baseline. These data will be presented today at the International Association for the Study of Lung Cancer (IASLC) 17th World Conference on Lung Cancer (WCLC) being held in Vienna.

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"These updated ALTA trial data show that with additional follow-up, median progression-free survival from brigatinib given post-crizotinib is now 15.6 months, and that this is the same whether assessed by the investigators or an independent review committee," said D. Ross Camidge, M.D., Ph.D., director of thoracic oncology at the University of Colorado. "Whether this is a reflection of broader suppression of potential resistance mutations, or its effects on protecting the central nervous system, or both, requires further investigation but by itself these progression-free survival data should be very encouraging for physicians and patients alike. These data really support the idea to pursue brigatinib, not just post-crizotinib, but also in the ongoing ALTA 1L study, which aims to assess its potential in the ALK-treatment naive setting."

The ALTA Trial

The ALTA (ALK in Lung Cancer Trial of AP26113) trial enrolled 222 patients with ALK+ NSCLC who had been treated with and experienced disease progression on their most recent crizotinib therapy. Patients were randomized one-to-one to receive either 90 mg of brigatinib once per day (QD) (Arm A), or 180 mg QD, preceded by a lead-in dose of 90 mg QD for seven days (Arm B). In addition, patients were stratified by presence of brain metastases at baseline and best response to prior crizotinib therapy.

The primary endpoint of the ALTA trial is investigator-assessed confirmed objective response rate (ORR) as measured by the Response Evaluation Criteria in Solid Tumors (RECIST). Key secondary endpoints include PFS, confirmed ORR assessed by an IRC, overall survival (OS), CNS response and PFS, duration of response, safety and tolerability.

Key Data from the ALTA Trial Update

Brigatinib Efficacy and Safety in ALK+ NSCLC Patients:
Clinical Data as of May 31, 2016 with IRC Data as of July 13, 2016

A total of 222 patients with ALK+ NSCLC treated with prior crizotinib therapy were randomized in the study (110 patients in Arm B at the 180-mg dose level with a seven-day lead-in at 90 mg and 112 patients in Arm A at the 90-mg dose level). The last patient was enrolled in the study in September 2015.
The median follow-up was 11 months in Arm B and 10.2 months in Arm A. ALTA trial data presented at the 2016 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) meeting, as of February 29, 2016, had median follow-up of 8.3 months in Arm B and 7.8 months in Arm A.
Investigator-assessed confirmed ORR in Arm B was 55 percent. IRC-assessed confirmed ORR in Arm B was 54 percent. Investigator-assessed confirmed ORR in Arm A was 45 percent. IRC-assessed confirmed ORR in Arm A was 49 percent.
In a subgroup analysis of confirmed ORR by baseline characteristics, there was no difference in confirmed ORR based on prior chemotherapy versus no prior chemotherapy.
The subgroup analysis by best response to prior crizotinib (partial or complete response versus other) suggests that patients who had achieved partial or complete responses on prior crizotinib treatment had a significantly higher confirmed ORR, compared with patients who did not achieve these responses.
Responses in Arm B included a confirmed partial response in a patient with the ALK kinase domain G1202R mutation at baseline, which is associated with resistance to all approved tyrosine kinase inhibitors (TKIs).
Median PFS was 15.6 months by both investigator assessment and IRC assessment in Arm B. Median PFS was 8.8 months by investigator assessment and 9.2 months by IRC assessment in Arm A.
Probability of OS at one year was 82 percent and 71 percent in Arm B and Arm A, respectively. The median OS had not been reached in either arm.
Of the 44 patients with measurable intracranial brain metastases at baseline, the IRC-assessed intracranial ORR was 67 percent (12/18) in Arm B and 46 percent (12/26) in Arm A.
The median IRC-assessed intracranial PFS was 18.4 months in Arm B and 15.6 months in Arm A.
The most common treatment-emergent adverse events (TEAEs; ≥ 30% of all patients, [Arm B/A]), regardless of relationship to treatment, were nausea (43%/36%), diarrhea (39%/21%), cough (36%/23%), headache (30%/28%) and increased blood creatine phosphokinase (CPK) (33%/11%).
TEAEs, grade ≥3, occurring in ≥4 percent of all patients (excluding neoplasm progression; Arm B/A), were increased CPK (10%/3%), hypertension (6%/6%), pneumonia (5%/3%) and increased lipase (3%/5%).
A subset of pulmonary adverse events (AEs) with early onset (median: Day 2; range: Day 1-9) occurred in six percent of all patients (grade ≥3 in 3% of patients); no such events with early onset occurred after dose escalation to 180 mg QD in Arm B.
Discontinuations and dose reductions due to AEs (Arm B/A) were 10 percent/three percent and 23 percent/eight percent, respectively. Discontinuations due to documented progressive disease (Arm B/A) were 23 percent and 30 percent.
"We are encouraged by the maturing efficacy and safety profile of brigatinib in this later data cut, which adds three months of follow up compared to the data presented at ASCO (Free ASCO Whitepaper)," stated Timothy P. Clackson, Ph.D., president of research and development and chief scientific officer at ARIAD. "These data are intended to be submitted to the European Medicines Agency in early 2017 for marketing approval. Pending regulatory review, we expect that brigatinib may become an important therapeutic option for the crizotinib-resistant population."

The poster presentation, "Brigatinib in Crizotinib-Refractory ALK+ NSCLC: Central Assessment and Updates from ALTA, a Pivotal Randomized Phase 2 Trial," (Abstract #4046, Poster ID P3.02a-013) will be presented today, Wednesday, December 7, 2016 from 14:30 – 15:45 GMT.

About Brigatinib

Brigatinib is an investigational, targeted cancer medicine discovered internally at ARIAD. Brigatinib received Breakthrough Therapy designation from the FDA for the treatment of patients with ALK+ NSCLC whose tumors are resistant to crizotinib, and was granted orphan drug designation by the FDA for the treatment of ALK+ NSCLC. The FDA has accepted brigatinib’s New Drug Application and has granted ARIAD’s request for Priority Review and set an action date of April 29, 2017 under the Prescription Drug User Fee Act (PDUFA). ARIAD intends to submit a Marketing Authorization Application (MAA) for brigatinib to the European Medicines Agency (EMA) in early 2017.

ARIAD has also initiated the Phase 3 ALTA 1L trial to assess the efficacy and safety of brigatinib in comparison to crizotinib in patients with locally advanced or metastatic ALK+ NSCLC who have not received prior treatment with an ALK inhibitor. More information on brigatinib clinical trials, including the expanded access program (EAP) for ALK+ NSCLC can be found here.

On December 7, 2016 Progenics Pharmaceuticals, Inc. (Nasdaq:PGNX), an oncology company developing innovative medicines and other products for targeting and treating cancer, reported that the first patient has been dosed in the Company’s Phase 2/3 clinical trial evaluating the diagnostic accuracy of its PSMA-targeted PET/CT imaging agent, 18F-DCFPyL (PyLTM) (Press release, Progenics Pharmaceuticals, DEC 7, 2016, View Source [SID1234516983]). PyL was discovered by a team led by Martin G. Pomper, M.D., Ph.D., William R. Brody Professor of Radiology at the Center for Translational Molecular Imaging at the Johns Hopkins University School of Medicine.

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"There exists a significant need for approved molecular imaging modalities with both high sensitivity and specificity to detect high risk recurrent or metastatic prostate cancer early," said Lawrence Saperstein, M.D., Assistant Professor, Department of Radiology and Biomedical Imaging, Chief, Nuclear Medicine Program Director, Nuclear Radiology Fellowship, Yale University School of Medicine, where the first patient was dosed. "We believe PyL, when used with a PET/CT scan, can provide treating physicians with more accurate disease detection, potentially leading to earlier diagnoses, more informed treatment decisions as well as the ability to monitor responses, and ultimately improved patient outcomes."

The Phase 2/3 study will enroll approximately 300 patients with high risk prostate cancer with recurrence or metastatic disease in the United States and Canada. Primary endpoints of the study include the assessment of sensitivity and specificity of PyL PET/CT imaging to detect prostate cancer in the prostate gland and regional lymph nodes, as well as sensitivity in sites of metastasis or recurrence. Secondary endpoints include safety and tolerability, detection rate, and pharmacokinetic parameters.

"This trial initiation represents a significant milestone for our PyL program, and is designed to help support registration of this novel imaging agent," stated Mark Baker, Chief Executive Officer of Progenics. "The early clinical data for PyL have been quite impressive, underscoring its potential to transform disease management for prostate cancer, and we look forward to further demonstrating its diagnostic performance as we advance the trial."

About PyL for PET Imaging of Prostate Cancer

PyL (also known as 18F-DCFPyL) is a clinical-stage, fluorinated PSMA-targeted PET imaging agent for prostate cancer that was discovered and developed at the Center for Translational Molecular Imaging at the Johns Hopkins University School of Medicine. A proof-of-concept study published in the April 2015 issue of the Journal of Molecular Imaging and Biology demonstrated that PET imaging with PyL showed high levels of PyL uptake in sites of putative metastatic disease and primary tumors, while rapidly clearing from other organs, suggesting the potential for high sensitivity and specificity in detecting prostate cancer while appearing to be safe and well tolerated.