On January 23, 2015 The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion for Jakavi (ruxolitinib) for the treatment of adult patients with polycythemia vera (PV) who are resistant to or intolerant of hydroxyurea (Press release Novartis, JAN 23, 2015, View Source [SID:1234501375]). If approved in the EU, ruxolitinib could provide the first targeted treatment option for these patients.

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PV is a chronic, incurable blood cancer associated with an overproduction of blood cells that can cause serious cardiovascular complications, such as stroke and heart attack[1]. In PV, patients with resistance to or intolerance of hydroxyurea are considered to have uncontrolled disease, which is typically defined as hematocrit levels greater than 45%, elevated white blood cell count and/or platelet count, and may be accompanied by debilitating symptoms and/or enlarged spleen[1],[3],[4]. Elevated white blood cell count and hematocrit are also associated with an increased risk of blood clots[5].

"This positive CHMP opinion is encouraging news for patients with polycythemia vera who need effective treatment options," said Alessandro Riva, MD, Global Head, Novartis Oncology Development and Medical Affairs. "If approved, ruxolitinib will be the first-ever targeted therapy for polycythemia vera in the EU, a positive step forward for the rare blood cancer community in Europe and a major development in Novartis’ continued commitment to help patients with high unmet needs."

In the EU, the European Commission generally follows the recommendations of the CHMP and delivers its final decision within three months of the CHMP recommendation. The decision will be applicable to all 28 EU member states plus Iceland, Norway and Liechtenstein. Global regulatory applications for ruxolitinib in PV are currently ongoing, and further regulatory filings are under review by health authorities. Ruxolitinib, which is marketed in the US by Incyte Corporation as Jakafi, received approval in December 2014 from the US Food and Drug Administration (FDA) for the treatment of patients with PV who have had an inadequate response to or are intolerant of hydroxyurea.

The CHMP recommendation was based on results from the pivotal Phase III RESPONSE clinical trial demonstrating that a significantly greater proportion of patients achieved the composite primary endpoint of hematocrit control (volume percentage of red blood cells in whole blood) without use of phlebotomy (a procedure to remove blood from the body to reduce the concentration of red blood cells) and spleen size reduction when treated with ruxolitinib compared to best available therapy (21% compared to 1%, respectively; p<0.0001)[1],[2]. In addition, a greater proportion of patients in the ruxolitinib treatment arm achieved complete hematologic remission, as defined by the modified 2009 European LeukemiaNet (ELN) criteria, when compared to the standard therapy arm (24% compared to 9%, respectively; p=0.003)[2]. The data also showed more patients treated with ruxolitinib had a durable primary response at week 48 compared to patients treated with standard therapy (19% compared to 1%, respectively; (p<0.0001)[2].

Overall, ruxolitinib was well tolerated, and non-hematologic adverse events (AEs) were consistent with those previously seen in ruxolitinib studies in PV and myelofibrosis[2],[6],[7]. Within the first 32 weeks of treatment, the most common Grade 3 or 4 hematologic AEs in the ruxolitinib treatment arm were anemia (1.8%) and thrombocytopenia (5.5%)[2]. The most common non-hematologic AEs were dizziness (15.5%), constipation (8.2%) and herpes zoster (6.4%)[2]. The three most frequent non-hematological laboratory abnormalities (any Grade) were hypercholesterolemia (30.0%), raised alanine aminotransferase (22.7%) and raised aspartate aminotransferase (20.9%), which were mainly Grade 1 and 2[2].

On January 23, 2015 Celgene reported that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion for ABRAXANE (paclitaxel formulated as albumin-bound nanoparticles, or nab-paclitaxel) in combination with carboplatin for the first-line treatment of non-small cell lung cancer in adult patients who are not candidates for potentially curative surgery and/or radiation therapy (Press release Celgene, JAN 23, 2015, View Source [SID:1234501378]).

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Lung cancer is the fourth most commonly diagnosed cancer in both men and women, however it is the leading cause of cancer-related mortality in Europe. Non-small cell lung cancer (NSCLC) is the most common form of lung cancer, accounting for 85 to 90% of all cases. The predominant cause of lung cancer is cigarette smoking, although environmental and occupational factors also can cause the cancer. Treatment options generally include systemic chemotherapy or protein kinase inhibitors. In the most advanced cases, only the symptoms of the disease can be managed; there is a clear need for innovative new medicines for the treatment of lung cancer.

"Progress in lung cancer will come first from early diagnosis with patients presenting promptly with symptoms and second, with new drugs that are well tolerated and improve on current therapies. Incremental steps can lead to a meaningful impact on patients and society, given the frequency and aggressiveness of lung cancer," says Dr. Mary O’Brien, Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust, UK. "The positive CHMP opinion for ABRAXANE in combination with carboplatin for the treatment of adult patients with NSCLC is a significant step toward bringing a new treatment option to patients in Europe. The clinical data show patients had a significant positive response rate to the treatment, combined with an established safety profile. The therapy has also shown a significant response benefit for a subset of patients with squamous cell lung cancer, where there have been limited treatment advances in recent years."

The positive CHMP opinion was based on the results of a multicenter, randomized, open-label study including 1,052 chemotherapy-naive patients with Stage IIIb/IV non-small cell lung cancer. The study compared ABRAXANE in combination with carboplatin versus solvent-based paclitaxel in combination with carboplatin as first-line treatment in patients with advanced non-small cell lung cancer. The primary efficacy endpoint, overall response rate, was significantly higher for patients in the ABRAXANE/carboplatin arm at 33%, compared with patients in the control arm, at 25%. The most common adverse reactions

(≥ 20%) of ABRAXANE in combination with carboplatin for NSCLC were anaemia, neutropenia, thrombocytopenia, peripheral neuropathy, nausea, and fatigue.

Tuomo Pätsi, President of Celgene in Europe, the Middle East and Africa (EMEA), said, "The positive CHMP opinion is the first opportunity for Celgene to play a role in helping patients with NSCLC have access to an important treatment option in Europe. The anticipated European Commission decision would be the third approved indication for ABRAXANE, underscoring the value of this medicine. We are committed to ensuring that patients who need ABRAXANE will gain access to it once approved by the European Commission."

The CHMP reviews applications for all 28 member states in the European Union (EU), as well as Norway, Liechtenstein and Iceland. The European Commission, which generally follows the recommendation of the CHMP, is expected to make its final decision within approximately two months. If approval is granted, detailed conditions for the use of this product will be described in the Summary of Product Characteristics (SmPC), which will be published in the revised European Public Assessment Report (EPAR).

ABRAXANE is not currently indicated for the treatment of metastatic NSCLC in the European Union.

On January 23, 2015 Progenics Pharmaceuticals reported that it has dosed the first subject in the resumed pivotal Phase 2 clinical study of Azedra in patients with malignant pheochromocytoma and paraganglioma (Press release Progenics Pharmaceuticals, JAN 23, 2015, View Source [SID:1234501379]). The trial is being conducted under a Special Protocol Assessment (SPA) with the U.S. Food and Drug Administration (FDA). Progenics acquired Azedra, a novel targeted cancer radiotherapy, in conjunction with its 2013 acquisition of Molecular Insight Pharmaceuticals (MIP).

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"Relaunching this study is a very important milestone for patients with metastatic and/or recurrent pheochromocytoma/paraganglioma," said Dr. Daniel Pryma, Associate Professor of Radiology and Clinical Director of Nuclear Medicine and Molecular Imaging at the University of Pennsylvania, a current investigator and lead investigator on the original trial. "This treatment has been generally well tolerated and the data emerging from the trial to date has been encouraging. I am pleased to be resuming this study and feel that Azedra could represent the best treatment in malignant pheochromocytoma/paraganglioma in the future."

The study is designed to evaluate the efficacy and safety of the administration of two therapeutic doses of Azedra in patients with malignant relapsed/refractory pheochromocytoma or paraganglioma, ultra-orphan cancers with limited treatment options. The primary objective of the study is to determine the clinical benefit of Azedra based on the proportion of study participants with a reduction of all antihypertensive medication by at least 50% for at least six months. The SPA requires that 25% of 58 evaluable patients achieve the primary endpoint.

In late 2010, MIP suspended enrollment in the trial to seek additional funding. The trial has now resumed to fulfill enrollment requirements under the SPA. The trial has treated 41 patients and 32% of those patients have achieved the primary endpoint. The most common adverse events observed have been gastroenterological and hematologic disorders.

"As a targeted cancer treatment, Azedra has the potential to improve outcomes in patients suffering from pheochromocytoma and paraganglioma," stated Mark Baker, CEO of Progenics. "We are focused on successfully completing this pivotal trial and look forward to completing patient enrollment by the end of 2015, building on the promising data seen to date, and advancing this promising candidate toward the marketplace."

Azedra has received Orphan Drug and Fast Track designations from the FDA.

On January 22, 2025 BPGbio, Inc., a leading biology-first, AI-powered clinical-stage biopharma company focused on mitochondrial biology and protein homeostasis, reported the presentation of new findings in pancreatic cancer subtyping from Project Survival (NCT2781012), the company’s seven-year longitudinal pancreatic cancer precision medicine clinical trial (Press release, BPGbio, JAN 22, 2015, View Source [SID1234649841]). The results will be presented at the ASCO (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium, being held January 23–25, 2025, in San Francisco, Calif.

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Aimed at improving pancreatic cancer survival rate, the multi-center clinical trial employed comprehensive biomarker discovery to understand patient survival, enabling the development of new diagnostic, therapeutic, and clinical support solutions. Leveraging the biology-first approach and causal AI capabilities of BPGbio’s proprietary NAi Interrogative Biology platform, researchers conducted a comprehensive multiomics analysis of plasma samples from 280 pancreatic ductal adenocarcinoma (PDAC) patients over seven years and found distinct molecular patterns correlated with both long-term and short-term survival outcomes.

"Pancreatic cancer is not a one-size-fits-all disease. One of the biggest challenges we face in treating it is the rapid progression of the disease, which often leaves us with little time to make critical decisions," said Madappa Kundranda, M.D., Ph.D., Chief of Division of Cancer Medicine, Banner MD Anderson Cancer Center, who was the principal investigator of the study. "Our research aims to address this by identifying pancreatic cancer subtypes quicker, allowing us to better select patients for clinical trials and, ultimately, develop more tailored treatments that can significantly improve patient outcomes."

Notably, elevated cholesterol metabolism was observed in long-term survivors, while reduced levels of specific lipids characterized short-term survivors, among other biomarkers. These findings offer the potential of non-invasive blood-based biomarker panels for precise patient stratification and more tailored treatment.

"This study identifies how critical it is to go beyond genomics in biomarker discovery in order to capture the biological diversity of patients which impacts therapeutic decisions," said Michael A. Kiebish, Ph.D., Vice President of Platform and Translational Sciences, BPGbio. "To effectively treat the patient, not just the disease, we must identify the right molecular signature, which can be revealed through advanced multi-omics technologies that provide a holistic view of the body’s biology."

Pancreatic cancer remains one of the deadliest cancers due to its typically late diagnosis and rapid progression. The current method of identifying tumor tissue subtypes such as ‘Cholesterogenic’ and ‘Classical’ is associated with improved survival, but tissue-based profiling poses challenges due to the invasive nature of sample collection and the time it takes to analyze tissue subtypes, relative to the quick advancement of the disease.

"At BPGbio, we believe that understanding differences in patient biology, such as between diseased and non-diseased populations, requires a systems medicine approach. These findings from Project Survival are a testament to the power of that perspective," said Niven R. Narain, Ph.D., President and CEO of BPGbio. "By expanding our focus beyond cancer tissues and by performing comprehensive molecular profiling on patient plasma, we unlock critical insights into pancreatic cancer biology. This approach enables us to move toward more tailored treatments for various categories of patients, bringing us closer to the ultimate goal of this meaningful project – survival."

ASCO-GI Presentation Details

Abstract #: 775
Abstract Title: Lipogenic and Metabolic Subtypes Define Survival Outcome in Pancreatic Adenocarcinoma Patients
In-Person Session Name: Poster Session B: Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract
In-Person Poster Session Date: January 24, 2025, 11:30 a.m. – 1 p.m. PST
Presenter: Madappa Kundranda, M.D., Ph.D.

About BPM31510

BPM31510IV is BPGbio’s lead candidate in late-stage development for aggressive solid tumors such as glioblastoma multiforme (GBM) and pancreatic cancer. Other topical and oral formulations of the investigational agent are also being developed as a potential treatment for several rare diseases. The compound has demonstrated a tolerable safety profile and shown potential clinical benefits across multiple disease indications. Validated by BPGbio’s NAi Interrogative Biology platform, BPM31510 induces a hallmark shift in the tumor microenvironment (TME) by modulating mitochondrial oxidative phosphorylation in aggressive tumors, leading to cancer cell death. In many mitochondrial diseases, restoring CoQ10 levels can overcome the effect of mutations in genes that lead to mitochondrial dysfunction. BPM31510 has been granted Orphan Drug Designation by the FDA for GBM, pancreatic cancer, and epidermolysis bullosa (EB), as well as Rare Pediatric Disease Designation for primary CoQ10 deficiency and EB.

On January 22, 2025 BlossomHill Therapeutics, Inc., a privately-held, clinical-stage biotechnology company focused on the design and development of small molecule medicines for treating cancer and autoimmune diseases, reported the first cohort of patients has been dosed in the SOLARA study (NCT06706076) (Press release, BlossomHill Therapeutics, JAN 22, 2015, View Source;and-HER2-Mutated-Non-Small-Cell-Lung-Cancer [SID1234649839]). SOLARA is a global, open label, dose escalation and expansion Phase 1/2 clinical trial assessing the safety, efficacy and tolerability of BH-30643 for locally advanced or metastatic non-small cell lung cancer (NSCLC) bearing EGFR or HER2 mutations.

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"EGFR-mutant lung cancer is one of the most common genomic subtypes of lung cancer globally and has been a major target of drug development in recent years, yet an unmet medical need remains for patients," said Dr. Geoff Oxnard, Chief Medical Officer of BlossomHill Therapeutics. "Our thesis is that the novel, macrocyclic design of BH-30643 will provide potent antitumor activity in a broader spectrum of EGFR-mutant lung cancers with reduced toxicity. Dosing the first Phase 1 patient cohort with BH-30643, our second molecule to enter the clinic, marks an important step toward our goal of providing patients with intentionally designed precision medicines."

About the SOLARA study

The Phase 1/2 SOLARA clinical trial evaluates BH-30643, a macrocyclic, reversible, mutant-selective OMNI-EGFR inhibitor for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) bearing EGFR or HER2 mutations. In preclinical studies, BH-30643 demonstrated potent antitumor activity spanning classical EGFR mutations (exon 19 deletions, L858R), atypical EGFR mutations (G719X, L861Q, S768I, etc.), exon 20 insertions, and HER2 mutations. The global study consists of a dose escalation part to identify Recommended Doses for Evaluation (RDE), followed by an expansion part to further evaluate BH-30643 across a range of EGFR and HER2 mutations. Additional details on the design and discovery of BH-30643 will be reported at an upcoming medical meeting.