3/15/2011

Cytheris Announces Study Results Indicating CYT107 Expands CD4 T-Cells

Cytheris SA, a clinical-stage biopharmaceutical company focused on research and development of new therapies for immune modulation, recently announced results of a multi-center Phase IIa study designed to investigate the potential of Interleukin-7 (CYT107) therapy to reconstitute CD4 T-cells in chronically HIV-1-infected patients whose CD4 T-cell counts remained low despite treatment with anti-retroviral-therapies (HAART). In addition to providing further evidence of the ability of IL-7 to stimulate the expansion of CD4 and CD8 T-cells in peripheral blood, the results demonstrate the importance of IL-7 in stimulating T-cell repopulation of the lymphoid tissue layer in the mucous membrane of the GI tract.

This effect, previously demonstrated in SIV-infected monkeys, is now confirmed by analysis of rectosigmoid biopsies in this study of HIV-infected patients defined as Immunological Non-Responders (INR). The analysis of these mucosal gut biopsies shows a 3.93-fold increase in CD4 T-cell counts following IL-7 treatment.

INSPIRE 2 is an open-label, multicenter Phase IIa study of CYT107 (IL-7) in chronically HIV-infected persons with CD4 T-cell counts between 101 to 400 cells/mm³ and plasma HIV RNA < 50 copies/mL. Twelve patients were enrolled and received 20 mcg/kg/week of CYT107 for 3 weeks. All were evaluated at the planned primary end point at week 12 (CD4 expansion).

The 12 enrolled patients received three weekly injections of CYT107 that were clinically well tolerated and without serious adverse events. Seven patients had transient increases in HIV RNA values (< 500 copies/mL). Median CD4 and CD8 T-cell counts were 272 and 554 cell/mm³ at baseline, increasing to 679 and 986 cells/mm³ at week 12, respectively. Mean values and paired t-tests were used for statistical analyses. CYT107 also decreased PD-1 frequency, a marker of T-cell exhaustion, in both CD4 and CD8 T-cells at W12 (p = 0.008 and p = 0.02). The decrease of PD-1 frequency on CD4 T-cells occurred as early as 2 weeks following the last administration of CYT107 (day 28, 1.8-fold decrease p = 0.003).

Twelve patients underwent immunophenotypic analyses of cryopreserved PBMC by flow cytometry at baseline and at week 12. A sustained increase of the gut homing receptor alpha 4 beta 7 integrin frequency on peripheral CD4 and CD8 T-cells was noted (1.4-fold in both) as early as day 7 post first CYT107 administration (t test; p < 0.002), with a peak increase at day 14 (p = 0.0001). At week 12, alpha 4 beta 7 remained elevated on peripheral CD8 (p = 0.009) on T-cells.

A subset of 4 patients underwent rectosigmoid biopsies both at baseline and between weeks 10 to 24. Mucosal gut biopsy analysis showed an increase in both CD4 T-cell frequency (38.85 +/- 9.07 pre vs. 53.08 +/- 11.52 post p = 0.0273) and counts (106 CD4/gr tissue: 2.29 +/- 1.15 pre vs. 9.01 +/- 7.85 post p = 0.1709).

The findings in the current study confirm previously reported results in SIV-infected monkeys showing the ability of IL-7 treatment to drive T-cells to the gut mucosa and facilitate their expansion.

In this study, not only did IL-7 confirm its potential for T-cell expansion, but it also showed its ability to send T-cells to the gut mucosa where it triggers local T-cell expansion. Numerous experimental and clinical studies confirm that T-cell reconstitution in the gut is critical for restoring control over the HIV virus.

The study therefore provides further evidence suggesting that administration of IL-7 may have an important effect on immunologic recovery in HIV-infected patients whose HAART regimens have been unsuccessful in restoring CD4 T-cells to a stable level. The sustained immunological efficacy suggests that a short course of IL-7 treatment may provide an important avenue for enhancing the immune system and inducing broad spectrum proliferative activity of CD4 and CD8 T-cells in the blood, lymph nodes, and small intestine, a key therapeutic effect in achieving long term disease stability in HIV-infected patients.

Recombinant human interleukin-7 (CYT107) is a critical immune-modulator for immune T-cell recovery and enhancement. As a growth factor and cytokine physiologically produced by marrow or thymic stromal cells and other epithelia, IL-7 has a critical and, at some steps, a non-redundant stimulating effect on T-lymphocyte development, notably on thymopoiesis and, downstream from the thymus, on homeostatic expansion of peripheral T-cells.

Clinical trials conducted on more than 160 patients in Europe, North America, South Africa and Taiwan have demonstrated the potential of IL-7 to expand and protect CD4 and CD8 T-cells. Currently, Cytheris is conducting multiple international investigations of IL-7 in HIV, HCV, HBV, post-BMT and cancer. Additional studies include a NIAID/NIH-sponsored trial (ICICLE) in idiopathic CD4 lymphocytopenia (ICL); a cancer vaccine study in children with Ewing’s sarcoma family of tumors or similar genetic tumors sponsored by US National Cancer Institute; and a multi-company/institutional study (EraMune 01) sponsored by ORVACS (the international HIV organization funded by the French Bettencourt Schueller Foundation) aimed at attacking the HIV viral reservoir.

Omthera Raises $33.9 Million to Fund Phase III Development

Omthera Pharmaceuticals, Inc., a privately held emerging specialty pharmaceuticals company, recently announced it has raised $33.9 million in a Series B funding round, led by new investor, New Enterprise Associates (NEA), one of the world’s leading venture capital firms. Existing investor, Sofinnova Partners, also participated in the financing. The capital raised will be used to fund the Phase III clinical development of Omthera’s novel Omega-3 fatty acid compound, Epanova, and for general corporate purposes. With this latest round, Omthera has raised approximately $40.4 million in venture capital since commencement of operations in 2009.

In a separate press release, Omthera also announced the company has initiated its pivotal Phase III EVOLVE (EpanoVa fOr Lowering Very high triglyceridEs) trial for Epanova, for the treatment of patients with very high triglycerides (greater than or equal to 500 mg/dL). In January 2011, the company announced data from its ECLIPSE (Epanova Compared to Lovaza In a Pharmacokinetic Single-dose Evaluation) trial, designed to evaluate the bioavailability of Epanova in comparison to Lovaza, the leading prescription Omega-3. Data from the trial showed that the bioavailability of Epanova was significantly superior to Lovaza.

“Omthera continues to generate very positive data, indicating Epanova has the potential to become the best-in-class therapy in the nearly $2 billion worldwide Rx Omega-3 market and an important treatment for the millions of patients suffering from high triglycerides,” said Jerry Wisler, President, Chief Executive Officer, and Co-Founder of Omthera. “As such, we are delighted to gain the support of a venture capital firm of the stature of NEA to lead this substantial new funding.”

New Enterprise Associates, Inc. is a leading venture capital and growth equity firm focused on helping entrepreneurs build transformational businesses across multiple stages, sectors, and geographies. With approximately $11 billion in committed capital, NEA invests in information technology, healthcare, and energy technology companies at all stages in a company’s lifecycle, from seed stage through IPO.

Founded in 2008, Omthera Pharmaceuticals, Inc. is a privatelyheld, emerging specialty pharmaceuticals company focusing its efforts on the clinical development of new therapies for dyslipidemia. Led by a team of experts with exceptional experience in developing new therapies for lipid disorders, Omthera is dedicated to developing innovative therapies for the millions of patients who have elevated triglyceride levels and increased risk of cardiovascular disease.

Avantor Completes Acquisition of RFCL Limited

Avantor Performance Materials Holdings S.A. recently announced it has completed its acquisition of RFCL Limited from ICICI Venture Funds Management Company Limited. Avantor, previously known as Mallinckrodt Baker, and its subsidiaries manufacture and market high-performance chemistries and materials around the world under two well-known and respected brand names, J.T.Baker and Macron Chemicals (formerly Mallinckrodt Chemicals). Terms of the deal were not disclosed.

Avantor identified RFCL as an attractive target to build on its current presence in the laboratory and pharmaceutical markets in India. With this acquisition complete, Avantor and its owner, an affiliate of New Mountain Capital, L.L.C., will provide RFCL with significant financial and strategic resources to support their growth initiatives.

Headquartered in New Delhi, RFCL is a leader in laboratory reagents and consumables as well as products for the medical diagnostics market in India. Through its Rankem division, RFCL offers more than 20,000 laboratory products to more than 5,000 customers across a variety of industries, including pharmaceuticals, biotech, research organizations, and educational institutions. RFCL’s Diagnova division offers approximately 2,000 products used by more than 6,000 customers primarily in the Indian in vitro diagnostics, medical devices, and life science research markets, which cater to hospitals, pathology laboratories, and blood banks.

“We see significant growth opportunities resulting from the combined resources of Avantor and RFCL, and we believe both Avantor and New Mountain share our values and our vision to realize these opportunities,” said Sushil Mehta, Managing Director of RFCL. “We are excited to join Avantor, and we look forward to enhancing the service and value we provide to our customers.”

“This acquisition will enable RFCL to take advantage of new opportunities,” said Prashant Purker, Executive Director at ICICI Venture. “This type of outcome is consistent with ICICI Venture’s way of investing, where we create value for all stakeholders. With this transaction, we have affected a complete exit from our investment in RFCL.”

“We look forward to working with the RFCL leadership team to capture the full potential from this combination,” said Jean-Marc Gilson, President and CEO of Avantor. “We believe that RCFL is the perfect partner for us as we expand our presence in this region and provide solutions for global customers in the laboratory, pharmaceutical, and electronic materials industries.”

RFCL Limited covers the expanse of Life Sciences industries including pharmaceuticals, biotechnology, R&D laboratories, life sciences, in vitro diagnostic facilities in clinical labs and hospitals through its two Strategic Business Units: Rankem and Diagnova. RFCL has evolved its corporate philosophy around Science, Solutions and Life. This philosophy is the foundation for RFCL’s vision: “Leveraging Science To Provide Solutions for a Better Life.” RFCL has approximately $50 million in annual sales.

Elan Announces First European Commission Approval of Injectable Treatment Using NanoCrystal Technology

Elan Drug Technologies (EDT), the leading drug delivery unit of Elan Corporation, plc, recently announced that the first injectable product using EDT’s NanoCrystal technology has been approved by the European Commission. XEPLION, Janssen-Cilag International NV’s long-acting injectable treatment for patients with schizophrenia, which uses EDT’s NanoCrystal technology, was approved by the European Commission.

“The European approval of XEPLION is an important milestone for our NanoCrystal technology as it marks the first long-acting injectable product approved by the European regulatory authorities using the technology,” said Shane Cooke, Executive Vice President and Chief Financial Officer of Elan and Head of EDT. “The versatility of our NanoCrystal technology enabled the development of a long-acting injectable antipsychotic, which is designed to help patients maintain continual treatment, reduce the likelihood of relapse, and thereby potentially improve their overall quality of life.”

On March 9, 2011, Janssen-Cilag International NV, one of the Janssen Pharmaceutical companies, announced the approval of XEPLION, a once monthly atypical antipsychotic injection, by the European Commission. XEPLION is indicated for maintenance treatment of schizophrenia in adult patients stabilized with paliperidone or risperidone. In selected adult patients with schizophrenia and previous responsiveness to oral paliperidone or risperidone, XEPLION may be used without prior stabilization with oral treatment if psychotic symptoms are mild to moderate and a long-acting injectable treatment is needed.

EDT’s NanoCrystal technology enables the formulation of poorly water-soluble compounds for all routes of administration. The technology allows for a ready-to-use, one-month duration, intramuscular injection formulation of paliperidone palmitate, which can be administered by healthcare professionals. The intramuscular injection is administered using a small bore needle and small volume syringe, thereby negating the need for a power injector. By applying the NanoCrystal technology to paliperidone palmitate, healthcare professionals will be able to provide patients with consistent medication coverage for 1 month, potentially allowing them to improve compliance for patients with schizophrenia.

NanoCrystal technology is a proprietary technology developed by EDT through Elan Pharma International Limited and other Elan affiliates. XEPLION is the fourth licensed product using Elan’s NanoCrystal technology that has been approved by the EMA.

Alliqua Successfully Completes Next Milestone in Transdermal Pain Patch Development

Alliqua, Inc., an advanced biomedical products company focused on the development and manufacturing of proprietary drug delivery and liver health technologies, recently announced the successful completion of its initial in vitro permeation study for its transdermal pain patch project. These results represent an important milestone in the development of a transdermal pain patch. Alliqua previously announced the successful completion of its dissolution study.

In the comparative in vitro permeation study, the Alliqua patch demonstrated mean cumulative drug permeation that was competitive with the market leading product for the treatment of pain associated with post-herpetic neuralgia (PHN) or shingles, a rising medical problem in the US and around the world as countries continue to struggle with increasingly elderly populations.

In the in vitro permeation study, multiple formulations were evaluated, with some achieving mean cumulative drug-permeation amounts much higher than the market leading product, indicating the potential for an improvement over the existing product. Alliqua believes that the results provide it with options to pursue a 505(b)(2) type of a NDA, along with a generic route for an ANDA. Based on the positive results, Alliqua will proceed to the next stage of its developmental program. Management estimates that global value of the PHN pain patch market is currently $1.4 billion.

“The continued success of our developmental efforts further validates our delivery platform, and our belief in the ultimate success in our specialized transdermal pain patch,” said Richard Rosenblum, President and Director of Alliqua. “Utilizing our proprietary hydrogel technology and our existing facilities, we believe Alliqua can become a high-quality, low-cost producer of this next-generation transdermal pain patch, with the possibility for significant market share.”

Alliqua also intends to continue pursuing a generic version of an existing pain management patch for the treatment of PHN. Management estimates that the total US market for pain management pharmaceuticals, exclusive of OTC products, totaled in excess of $20 billion in 2009, with the market for existing prescription pain patches in excess of $1 billion in the US alone.

According to the Centers for Disease Control, approximately 1 million cases of shingles occur in the US annually, and approximately 20% of shingles cases result in PHN. Alliqua’s patch technology enables the delivery of drugs and active ingredients directly through the stratum corneum, avoiding first pass of the digestive system and the liver.

Alliqua, Inc., is an advanced biomedical products company focused on the development and manufacturing of proprietary technologies in the fields of drug delivery, advanced wound care, and liver health preservation. Through its wholly owned subsidiary, Alliqua BioMedical, Inc., Alliqua intends to develop active ingredient and transdermal drug delivery products, primarily utilizing the proprietary hydrogel technology platform of AquaMed Technologies, Inc., Alliqua’s subsidiary. AquaMed manufactures custom hydrogels used for transdermal drug delivery, wound care, medical diagnostics, and cosmetics.

Ricerca Biosciences Announces Strategic Collaboration With Fulcrum

Ricerca Biosciences, an integrated preclinical CRO providing services to the biopharmaceutical industry, recently announced a strategic partnership with Fulcrum Pharma, an Aptiv Solutions company, a leading provider of drug development consulting and regulatory services essential to progress a development program from research to product approval. The collaboration provides unique, value-added capabilities to biopharmaceutical companies by creating a streamlined and efficient process to move a candidate from development to clinical evaluation.

“The Fulcrum Pharma collaboration is an attractive and exciting proposition for Ricerca and our clients,” said Ian Lennox, CEO of Ricerca. “Fulcrum Pharma brings deep experience in IND authorship and regulatory approval, which fits well with Ricerca’s preclinical services in discovery pharmacology, chemical development, and drug safety assessment. The relationship greatly expands our ability to serve our clients who are preparing for regulatory submission anywhere in the world.”

“The collaboration offers our early stage clients a streamlined service to move efficiently through preclinical development to creation of high-quality IND submissions,” added Patrick K. Donnelly, Aptiv Solutions’ Chairman and CEO. “This approach, coupled with our expertise in adaptive clinical trial design, will provide our clients with the ability to accelerate the development of their products and stay ahead of the competition.”

Ricerca Biosciences provides the full range of preclinical services from early discovery medicinal chemistry, compound screening, profiling, and lead optimization through full drug safety, metabolism, and efficacy development support, as well as clinical supply and commercial API production capability. Fulcrum Pharma is a global leader in the provision of strategic and operational regulatory support to assist clients in the authorship and approval of regulatory submissions. Aptiv Solutions is a global biopharmaceutical and medical device development services company focused on recognizing, understanding, and enabling clients to capitalize on rapid and fundamental changes facing companies developing products in the pharmaceutical, biotech, and medical device market.