FDA panel gives a thumbs up to Amgen's T-Vec for melanoma April 29, 2015 | By John Carroll Amgen's regulatory team for talimogene laherparepvec (T-Vec) was grilled by a group of outside FDA experts who picked up on some major questions regarding the Phase III melanoma study that was used to back its new drug application. A vigorous defense of the drug, though, helped make a winning case for the therapy, which was ultimately supported by all but one member of the panel. There was considerable sentiment in favor of restricting the drug to certain patient groups, with some of the panelists expressing their frustration that they couldn't register a vote regarding the low likelihood that the drug would work for visceral (internal) tumors or later-stage patients. At the end of the day, though, the expanded panel voted 22 to 1 that the drug has a favorable risk/benefit profile. T-Vec is injected directly into tumors, where it replicates and then ideally ruptures the tumor cells. The rupture causes the release of antigens which in turn spur the immune system response--a kind of one-two punch that represents a different approach to treating melanoma. "There are clearly patients in my clinic I'd like to use this for," noted Patrick Hwu, a professor in the department of Melanoma Medical Oncology at the University of Texas MD Anderson Cancer Center who voted to support T-Vec. A number of the experts noted that the more "arrows" they had in their therapeutic quiver, the better off patients would be. The final decision is being left in the hands of the FDA, though today's vote would make T-Vec an odds-on favorite for approval. If so, Amgen ($AMGN) is on track to score several possible approvals this year, marking some advances after analysts like Geoffrey Porges have criticized the Big Biotech's development strategy and heavy research costs. The day started with FDA reviewers offering some skeptical remarks about their interpretation of the late-stage data. "The evidence that talimogene has a systemic effect was limited and difficult to calculate," FDA reviewer Robert Le told the committee. In particular, committee members noted that there were widely different response rates among different subgroups in the study. For Le, "first line or less advanced patients may have responded better." "Subjects with small lesions may be more likely to respond," he added, "larger lesions less likely." Abigail Luo, who specifically focused on mixed survival benefits, also raised concerns about the removal of 7 patients from the control arm. That change may have skewed the results in favor of the drug arm, raising the prospect that investigator bias may have played a role in shaping the results. And her review "increases uncertainty of overall survival benefits" for the drug arm, though patients in the drug arm did live more than 4 months longer on average than the comparator arm. Another concern was viral "shedding," in which healthcare workers and others could be exposed and infected by the live herpes simplex virus used in T-Vec.
Amgen applied for full approval of T-Vec based on durable response. Amgen execs noted that the comparator treatment in the study, GM-CSF, has some effect, which may have influenced results as well. So overall, the observed results do give an idea of who benefits the most from T-Vec, they noted. Subgroup analysis--which tends to raise all sorts of issues related to statistical significance--also showed some dramatic differences in response, with first-line patients, for example, doing better than second-line patients. Amgen had some big factors playing in its favor. The experts, like the agency, lean heavily on the side of providing physicians and patients as many treatment choices as possible, particularly in the absence of serious toxicity issues. Treating late-stage cancer patients isn't an ideal world, and attitudes to safety and efficacy can be far more flexible in oncology than, say, chronic diseases. The agency also keeps an open mind when it comes to last-ditch efforts, after other treatments have failed.
"Metastatic melanoma continues to be a major challenge to patients and caregivers," Amgen stated after the vote Wednesday. "It is a complex and heterogeneous disease that often requires the use of multiple treatment modalities. Despite recent advances, the five-year survival rate for metastatic melanoma is still unacceptably low and nearly 10,000 patients are expected to die in the U.S. this year. It is clear from today's discussion that the committee recognized the importance of the need for new therapeutic options for patients with metastatic melanoma. We look forward to talking with the FDA about how to best make talimogene laherparepvec monotherapy available to patients as they complete their review of the Biologics License Application."
治療皮膚癌 基改皰疹病毒試驗見成效 2015-05-27 18:51:51根據今天公布的臨床試驗結果，基因改造的皰疹病毒可有效對抗皮膚癌。法新社華盛頓27日報導，研究結果顯示，以T-VEC（Talimogene Laherparepvec）藥物治療後，患者存活時間可大大增加，這可望讓美國與歐洲藥物管制機構核准。試驗中超過16%的病患接受施打後，出現維持超過半年的治療反應；相較之下，對照組只有2%的病患可達相同效果。（陳淑娟編）【中央網路報】
Amgen to Acquire BioVex for Up To $1B, to Obtain Cancer-Killing Virus Therapy Luke Timmerman 1/24/2011 Amgen is sticking its scientific neck out, and potentially $1 billion of its cash, to buy a company in Woburn, MA that hopes to deliver the first FDA-approved virus engineered to specifically kill cancer cells. Thousand Oaks, CA-based Amgen (NASDAQ: AMGN) said today it has agreed to pay $425 million upfront, plus another $575 million in additional development and sales milestones, to obtain privately-held BioVex. Amgen, which has significant research and development operations in South San Francisco, Seattle, and Cambridge, MA, said it expects to close this deal before the end of March. BioVex, which we last wrote about in November 2009, raised $70 million in venture capital that year to carry out the final steps of development with its oncolytic virus therapy. BioVex is seeking to harness decades of science, in which researchers have sought to genetically modify viruses to replicate inside tumors, while sparing healthy tissue. Once inside, the treatment (OncoVex GM-CSF) is supposed to cause tumor cells to burst. But it doesn't stop there—it is also designed to provoke the immune system to mount an attack in the cancerous growth itself, and hunt down any cancer cells that have spread throughout the body. BioVex, as I noted in these pages just over a year ago, has attracted interest from scientists and investors based largely on one study of 50 patients with forms of melanoma, a deadly skin cancer, that have spread through the body. That study found that 13 of the 50 patients (26 percent) had their tumors shrink after they got the BioVex treatment. Even more interesting, eight of the 13 initial responders had their tumors completely disappear, and their responses were long-lasting. Although patients who entered the trial had terminal diagnoses, usually giving them six to nine months to live, according to BioVex CEO Philip Astley-Sparke, more than half of the patients were alive after one year (58 percent) and two years (52 percent), according to data presented at the American Society of Clinical Oncology in June 2009. Side effects were mostly mild-to-moderate flu-like symptoms, researchers said. The company is now in the midst of gathering more proof from a Phase III clinical trial which, if successful, could be the basis for it to win FDA approval of the first such oncolytic virus therapy. BioVex is running a trial expected to enroll as many as 430 patients, according to a posting on clinicaltrials.gov. The goal will be to show the BioVex drug offers an advantage in tumor shrinkage that lasts six months or more, compared to an immune-boosting compound."OncoVex has demonstrated encouraging anti-tumor activity in clinical studies for the treatment of melanoma and head and neck cancer, and BioVex is currently enrolling patients into pivotal Phase 3 trials in both indications," said Roger Perlmutter, Amgen's executive vice president of R&D, in a statement. "Amgen is particularly excited about joining with BioVex and its talented staff to focus on advancing this late-stage investigational therapy, with the hope of bringing it to market within the next few years." No one has ever developed such an oncolytic virus treatment for cancer, although many, such as South San Francisco-based Cell Genesys, have tried before. While BioVex may have the candidate most advanced in clinical trials at the moment, it's not the only company generating new interest in the field. San Francisco-based Jennerex Biotherapeutics, led by a veteran of the early days at Emeryville, CA-based Onyx Pharmaceuticals, is also hot on the trail. So is Calgary, Canada-based Oncolytics Biotech. Amgen has been pushing for years to become a bigger player in anti-tumor drug development, after making its fortune largely on treating some of the side effects of cancer chemotherapy. It won FDA approval in 2006 for panitumumab (Vectibix), and saw limited success. Last year, it followed that up with an FDA clearance of denosumab (Xgeva) as a treatment for bone-related tumors. We'll find out soon enough whether this new bet on oncolytic viral therapy puts Amgen on the leading edge of a new field of science, or ends up being a costly debacle.
Biovex Formed in 1999, Biovex is a private biotech company, based near Oxford, developing a new class of potent vaccines to treat and prevent cancer and certain viral diseases. The company has two vaccine platforms; OncoVEX and ImmunoVEX, and a functional genomics platform for gene target validation in neurons and other tissues (NeuroVEX). The Company`s lead product has completed Phase I clinical trials with Phase II studies in melanoma, breast cancer and head and neck cancer begun in October 2006. Amgen acquired Biovex in February 2011.
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