On April 17, 2018 Johnson & Johnson reported a strong first quarter with $20 billion in sales that was fueled by significant growth in its pharmaceuticals business (Press release, BioSpace, APR 17, 2018, View Source [SID1234525487]).

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About half of the healthcare giant’s quarterly sales was driven by the company’s pharma business. In its quarterly report, the healthcare giant said pharmaceutical sales generated $9.8 billion in the first quarter. That was an increase of 19.4 percent over the same period last year. The bulk of the company’s pharma sales were made overseas, according to the data. J&J said international sales increased by 33.1 percent and domestic sales increased 9.9 percent.

The company noted that strong sales were driven by drugs such as Darzalex (daratumumab), a treatment for multiple myeloma, Tremfya (guselkumab) a treatment for moderate to severe plaque psoriasis and blood-cancer treatment Imbruvica (ibrutinib). During the first quarter J&J filed a supplemental New Drug Application for Imbruvica as a treatment for Waldenström’s macroglobulinemia.

Johnson and Johnson noted other strong-performing drugs including Zytiga (abiraterone acetate), which is used for the treatment of metastatic, castration-resistant prostate cancer. During the quarter Zytiga gained approval for an additional indication as at treatment of metastatic high-risk castration-resistant prostate cancer. Two other strong performers included inflammatory disease treatment Stelara (ustekinumab) and the anti-blood clotting drug Xarelto.

Also, during the first quarter, J&J gained approval from the U.S. Food and Drug Administration for Erleada, an oral androgen receptor inhibitor for the treatment of patients with non-metastatic castration-resistant prostate cancer.

Johnson & Johnson noted that the pharmaceutical business gained a 7.6 percent boost from the company’s 2017 $30 billion acquisition of Swiss-based Actelion, which manufactures Tracleer, a drug used to treat pulmonary arterial hypertension a form of high blood pressure in the arteries of the lungs. While J&J saw an increase in earnings from the deal, the company noted that it discontinued development of one of the drug candidates picked up in that acquisition. In its earnings report, J&J said it terminated development of cadazolid, a Phase III program for the treatment of clostridium difficile-associated diarrhea. Months after the deal was announced Actelion disclosed that cadazolid saw mixed results in two identical studies. The drug hit the mark in reducing diarrhea in patients in one study but failed to do so in a joint-study.

Alex Gorsky, chief executive officer of Johnson & Johnson, said the company’s pharmaceutical business delivered robust returns for the company.

In addition to its strong pharma showing, J&J said its medical device business saw sales of $6.8 billion for the first quarter, which represented an increase of 7.5 percent over the prior year.

Not only did J&J see strong revenues from its pharma business, Gorsky added that the company is also benefitting from a revamping of U.S. tax laws. He said the new legislation that reduced corporate tax rates in the United States will allow the company to invest more than $30 billion in research and development, as well as capital investments over the next four years. Gorsky said that investment is an increase of 15 percent over the previous four years.

On April 17, 2018 Alpine Immune Sciences, Inc. (NASDAQ:ALPN), a leading immunotherapy company focused on developing treatments for cancer and autoimmune/inflammatory diseases, reported preclinical study results of its ALPN-202 immuno-oncology program (Press release, Alpine Immune Sciences, 17 17, 2018, View Source [SID1234525447]). ALPN-202 will be the second product candidate to come out of the company’s proprietary scientific platform following ALPN-101, which is projected for an IND filing in the fourth quarter of 2018.

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ALPN-202 is designed to antagonize PD-L1 and CTLA-4 while also providing CD28 costimulation. Recent literature suggests the lack of CD28 costimulatory signaling may be a principal reason why many tumors do not respond to PD-L1 or CTLA-4 blockade. ALPN-202’s ability to agonize the costimulatory receptor CD28 potentially improves the immune system’s response to cancer.

Alpine used its proprietary scientific platform to engineer Variant Ig Domains (vIgDs) based on CD80. Single vIgD proteins were created capable of binding PD-L1, CTLA-4, and CD28. These vIgDs were then fused to an Fc backbone and used in various in vitro and in vivo studies to characterize functional activity and assess anti-tumor activity in mice implanted with human PD-L1 transduced tumors. Results showed:

ALPN-202 eliminated tumors in most mice (73% or 8/11 tumor free) compared to durvalumab, an FDA-approved anti PD-L1 antibody (18% or 2/11 tumor free), and controls (0/11 tumor free).
Importantly, those mice tumor free after receiving ALPN-202 were re-challenged with tumor and 100% of them were resistant to the newly-implanted cells without receiving additional doses of therapy, suggesting the potential for ALPN-202 to induce anti-tumor memory.
ALPN-202 elicited CD28 costimulation only in the presence of PD-L1.
Scientific Support and Rationale for ALPN-202
PD-1/PD-L1 inhibitors likely are most effective only when sufficient T cell activating signals, such as via CD28 costimulation, are present. Indeed, recent research demonstrated CD28 costimulation appears to be required for PD-1 inhibition to rescue exhausted T cells in some settings (Science 355:1423, 2017), yet the CD28 ligands CD80 and/or CD86 are often poorly expressed in tumor microenvironments. Because it provides both checkpoint blockade and CD28 costimulation, the ALPN-202 program is therefore well positioned to potentially be a more potent and broadly applicable therapeutic.

"Previously published data suggest PD-1 blockade requires CD28 costimulation to work, at least in some cancers. The preclinical data we are presenting at AACR (Free AACR Whitepaper) indicate the ALPN-202 program proteins are capable of delivering both with a single molecule," said Stanford Peng, M.D., Ph.D., Executive Vice President of Research and Development and Chief Medical Officer of Alpine. "Additionally, these data demonstrate we can modulate three targets (PD-L1, CTLA-4, and CD28) with a single domain (in contrast to the need for multiple targeting domains for other therapeutic formats like bi- or tri-specific antibodies), demonstrating the potential promise of our versatile scientific platform."

"Our goal in oncology is to develop paradigm-shifting therapeutics that meaningfully improve upon existing therapies like PD-1/PD-L1 inhibitors," said Mitchell H. Gold, M.D., Executive Chairman and Chief Executive Officer of Alpine. "The preclinical data presented at AACR (Free AACR Whitepaper) show ALPN-202 antagonizes PD-1 and CTLA-4, and provides a CD28 costimulatory signal, resulting in a potent anti-tumor response. As we drive the ALPN-202 program towards the clinic in 2019, we believe we can create the next generation of immuno-oncology therapeutics with novel mechanisms of action using our proprietary scientific platform."

On April 17, 2018 amcure, a biopharmaceutical company developing first-in-class cancer therapeutics, reported pre-clinical results of its lead drug candidate, AMC303 (Press release, amcure,APR 17, 2018, View Source [SID1234525445]). The data showed the strong anti-tumor and anti-metastatic effects in various epithelial tumor cells by binding of AMC303 to the extracellular domain of CD44v6. The research was presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2018 in a poster entitled ‘The allosteric inhibitor of CD44v6 AMC303 blocks c-MET, Ron and VEGFR-2 dependent signaling and cellular processes’.

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"The results presented in this study emphasize the importance of CD44v6 inhibition in cancer and the potential of this approach to improve the chances against this disease," said Klaus Dembowsky, MD, PhD, CEO of amcure. "Not only did we show strong anti-cancer effects for AMC303, but we gained new mechanistic insights into the role of AMC303 in inhibition of one of the key drivers of metastasis, Epithelial-Mesenchymal-Transition (EMT). We look forward to substantiating the strong preclinical data sets for AMC303 with results from our current and future clinical trials."

The CD44 family of transmembrane glycoproteins comprises several variants that are involved in many cellular processes. The isoform CD44v6 has been shown to play a major role in tumor growth and metastasis. In this study, the amcure research team has shown that blocking CD44v6, an essential coreceptor for the receptor tyrosine kinases VEGFR-2, c-MET and RON by AMC303, interferes with several key steps in tumor progression and metastasis including EMT, cell migration and invasion. This novel mode of action results in strong anti-tumor and anti-metastatic effects of AMC303.

About AMC303
amcure’s lead compound, AMC303, is being developed as a potential treatment for patients with advanced and metastatic epithelial tumors, e.g. pancreatic cancer, head and neck cancer, gastric cancer, colorectal cancer, breast cancer and lung cancer. AMC303 has a high specificity for inhibiting CD44v6, a co-receptor required for signaling through multiple cellular pathways (c-Met, VEGFR-2, RON) involved in tumor growth, angiogenesis and the development and regression of metastases.

AMC303 has demonstrated strong effects in various in vitro and in vivo assays.

On April 17, 2018 Novocure (NASDAQ: NVCR) reported positive top-line results from its STELLAR phase 2 pilot trial in mesothelioma demonstrating clinically meaningful improvements in overall survival and progression free survival among patients who received Tumor Treating Fields plus standard of care chemotherapy, pemetrexed and cisplatin or carboplatin, compared to historical control data of patients who received standard of care chemotherapy alone (Press release, NovoCure, APR 17, 2018, View Source [SID1234525444]).

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The final data exceeded the results of the interim analysis presented in December 2016 at the International Association for the Study of Lung Cancer (IASLC) 17th World Conference on Lung Cancer for all efficacy endpoints. No device-related serious adverse events were reported. Novocure will submit the full data for presentation at an upcoming medical conference.

"We are extremely pleased with these top-line results, which bring us one step closer to realizing the potential for a new treatment for mesothelioma patients in desperate need," said Dr. Eilon Kirson, Novocure’s Chief Science Officer and Head of Research and Development. "Mesothelioma is the first torso indication for which Novocure will pursue FDA approval. The STELLAR data reinforce our belief that Tumor Treating Fields may be a broadly applicable platform technology for the treatment of solid tumors. We look forward to sharing the detailed results of the study with the lung cancer community at an upcoming medical conference."

Novocure previously received Humanitarian Use Device (HUD) designation for the use of Tumor Treating Fields for the treatment of pleural mesothelioma. Based upon the final STELLAR data, Novocure plans to submit a Humanitarian Device Exemption (HDE) application to the FDA for approval. An approved HDE would allow Novocure to market Tumor Treating Fields in combination with standard of care chemotherapy as a treatment for pleural mesothelioma in the United States.

Tumor Treating Fields in combination with standard of care chemotherapy is an investigational treatment for pleural mesothelioma and is not approved for this indication. These results are preliminary top-line data and are subject to further analysis.

About STELLAR

The STELLAR trial is a phase 2 pilot single-arm, open-label, multi-center trial designed to test the efficacy and safety of Tumor Treating Fields in combination with standard of care chemotherapy, pemetrexed combined with cisplatin or carboplatin, in 80 patients with unresectable, previously untreated malignant pleural mesothelioma. The historical control for this trial is the results of the 2003 pemetrexed phase 3 FDA registration trial.

An interim analysis of the first 42 patients enrolled in the trial with an average follow-up time of 11.5 months was presented at the International Association for the Study of Lung Cancer in December 2016. The one-year survival rate of patients treated with Tumor Treating Fields combined with pemetrexed and cisplatin or carboplatin was 80 percent (compared to 50 percent in pemetrexed and cisplatin-alone historical controls). Median progression free survival in the Tumor Treating Fields-treated group was 7.3 months (compared to 5.7 months in pemetrexed and cisplatin-alone historical controls) and one-year survival rate was 79.7 percent (compared to 50.3 percent in pemetrexed and cisplatin-alone historical controls). Median overall survival had not yet been reached. No device-related serious adverse events had been reported to date.

About Mesothelioma

Malignant mesothelioma is a rare thoracic solid tumor cancer that has been strongly linked to asbestos exposure. It has a long latency period of at least 20-30 years following exposure, and global incidence is still increasing in countries where asbestos is still in use. There are approximately 3,000 new cases of mesothelioma annually in the United States. The prognosis of mesothelioma patients is very poor, with a median overall survival of approximately 12 months in most reported studies.

On April 17, 2018 VBI Vaccines Inc. (Nasdaq: VBIV) ("VBI"), a commercial-stage biopharmaceutical company developing next-generation infectious disease and immuno-oncology vaccines, reported that, upon review of all safety data from the fully enrolled, low-dose patient cohort of the ongoing Phase 1/2a clinical study of VBI-1901 in recurrent Glioblastoma (GBM), the independent Data and Safety Monitoring Board (DSMB) unanimously recommended the continuation of the study without modification (Press release, VBI Vaccines, APR 17, 2018, View Source [SID1234525443]).

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Following this recommendation, VBI has initiated enrollment in the intermediate-dose arm of the dose-escalation phase of this study. Two additional, pre-specified DSMB reviews will occur after the completion of enrollment in the intermediate-dose study arm and the high-dose study arm, respectively.
"We are encouraged by the safety profile of this candidate so far and are excited to continue enrollment in the intermediate dose cohort of this Phase 1/2a study, our first clinical study in immuno-oncology," said Jeff Baxter, VBI’s president and CEO. "In recurrent GBM, a devastating CMV-associated tumor, patients have few effective treatment options, and we believe that VBI-1901 has the potential to stimulate immune responses critical to boosting anti-tumor immunity."

About the Phase 1/2a Study Design
VBI’s two-part Phase 1/2a study is a multi-center, open-label, dose-escalation study of VBI-1901 in approximately 28 patients with recurrent GBM:

Part A: Dose-escalation phase to define the safety, tolerability, and optimal dose level of VBI-1901 in recurrent GBM patients. This phase is expected to enroll up to 18 patients in three dose cohorts.

Part B: A subsequent extension of the optimal dose level, as defined in the dose escalation phase. This phase is expected to enroll an expanded cohort of approximately 10 additional patients.
VBI-1901 is administered intradermally and is adjuvanted with granulocyte-macrophage colony-stimulating factor (GM-CSF), a potent adjuvant that mobilizes dendritic cell function. Patients in both phases of the study will receive vaccine every four weeks until tumor progression.
Additional information, including a detailed description of the study design, eligibility criteria, and investigator sites, is available at ClinicalTrials.gov using identifier NCT03382977.
About VBI-1901 and GBM
VBI-1901 is a novel immunotherapy developed using VBI’s eVLP technology to target two highly immunogenic cytomegalovirus (CMV) antigens, gB and pp65. Scientific literature suggests CMV infection is prevalent in multiple solid tumors, and recent research has demonstrated that an anti-CMV dendritic cell vaccination regimen may extend overall survival in patients with GBM. Additionally, recent preclinical studies confirmed that VBI-1901 may be a potent, "off-the-shelf" therapeutic vaccine.
Glioblastoma is among the most common and aggressive malignant primary brain tumors in humans. In the U.S. alone, 12,000 new cases are diagnosed each year. The current standard of care for treating GBM is surgical resection, followed by radiation and chemotherapy. Even with aggressive treatment, GBM progresses rapidly and is exceptionally lethal, with median patient survival of less than 16 months.