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Talon to seek accelerated approval of Marqibo Talon Therapeutics (OTCBB:TLON) plans to submit a new drug application with the FDA for priority review of its Marqibo oncology drug in the second quarter this year and is hoping for accelerated approval in the final quarter of the year. “We are seeking accelerated approval based on data from our Phase 2 RALLY study where we demonstrated a 35% overall response rate using single agent Marqibo as third, fourth, fifth or sixth line treatment,” CEO Dr. Steven Deitcher says in an exclusive interview with BioTuesdays.com. “This is the most heavily pretreated and advanced Acute Lymphoblastic Leukemia (ALL) population that has ever been described or studied in the literature.” Dr. Deitcher, a hematologist and oncologist calls a 35% response rate in this population “very impressive”, adding that about 20% of the patients in the trial achieved a complete response, meaning “elimination of all blood, bone marrow and radiographic evidence of their disease, along with a very meaningful median survival.” Dr. Deitcher points out that the best that has ever been reported with a single agent therapy in a similar or even in a less heavily pretreated population was a 4% complete response rate. “So, what we’ve done with single agent Marqibo, we think, will offer a transformational opportunity for this very sick population of adult patients and a means of bridging to getting a stem cell transplant which could be curative.” People with adult ALL have a poor prognosis, with a five-year survival rate of about 7%. Third-line therapies induce few responses and are highly toxic, because patients already have been heavily pretreated with up to eight different drugs during first and second therapy. And fourth-line or greater therapy is expected to induce no response, he adds. “We believe people with ALL, like the population studied in RALLY, represents a very appropriate unmet medical need and an untapped commercial opportunity to bring our drug out into the field,” says Dr. Deitcher. Marqibo is what he calls a “smart bomb” of the widely used chemotherapy vincristine, which is encapsulated in unique liposome nanoparticles, which Talon refers to as Optisomes. Conventional vincristine is widely used in adult ALL, childhood ALL, across the spectrum of lymphomas, multiple myeloma and many childhood solid tumors. In the RALLY study, Talon, formerly Hana Biosciences, delivered two to three times the amount of vincristine per dose than with standard treatment. “That’s the magic,” he says. “You give more, and you give it in a more targeted fashion.” Talon’s ultimate goal is to have Marqibo replace millions of doses of standard vincristine chemotherapy given each year worldwide. “The one and only drug that every single one of our patients received prior to getting into our studies was vincristine.” If Marqibo is cleared by the FDA for use in additional, larger indications, Talon is looking at a multibillion-dollar potential. “The path we elected to follow was to provide a better vincristine,” Dr. Deitcher says. “This way, we will be able to provide a turbo charged version of vincristine to physicians who are already comfortable using the drug in their patients. Our way is designed to give them more bang for the dose.” Marqibo’s Phase 2 data and its commercial potential played a large role in Warburg Pincus and Deerfield Management, an existing shareholder of Talon, agreeing to inject up to $100 million to purchase Talon convertible preferred shares in three tranches. The first tranche of $40 million closed last June, with Warburg Pincus having 90% of it. The preferred shareholders also have an option to purchase up to another $20 million in preferred shares prior to the FDA decision on Marqibo, and if Marqibo receives approval, they have another option to purchase up to a further $40 million. Talon CFO Craig Carlson says many funds were reluctant to invest in the company, because it was using Phase 2 clinical data to seek approval for Marqibo. “Warburg Pincus had previously invested in Allos Therapeutics (NASDAQ:ALTH), which was in the same situation as we were, in terms of having data from a Phase 2 trial as their pivotal data,” he recalls. “So they went through that minefield with Allos, and it received an approval from the FDA.” The FDA gave Allos accelerated approval of Fototyn in 2009 for use as a single agent for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma. There are other examples of the FDA approving a Phase 2 product, including clofarabine for the treatment of relapsed pediatric ALL and nelarabine for pediatric and adult T-cell ALL. They had complete response rates similar to Marqibo. “So, our data and our approach are an established path forward,” Dr. Deitcher says. “If you have compelling data and no safety issues, our argument is that you should make these drugs available to these deathly ill individuals as long as your Phase 2 data adequately predicts meaningful clinical benefits.” He says the investment by Warburg Pincus was a “tremendous external validation, not only of Marqibo, but also of the people and the team behind it. The financial commitments are exactly what we needed to be focused on reaching the ultimate goal of getting our drug approved.” In the Phase 2 trial, the median age of patients was 32. “These are mostly young people with families, and there’s a lot of value in trying to save those lives,” Dr. Deitcher says. In addition to statistical measures in the Phase 2 data, the trial produced meaningful patient outcomes. Among other things, 11 patients received stem cell transplants after being treated with Marqibo, and five patients had an overall survival of greater than one year. “The fact that we were able to clear all evidence of leukemia from the blood in 63% of patients after just one dose of Marqibo, and the fact that we had excellent response rates even in those patients who had their solid organs infiltrated with leukemia just shows that this is a very effective and very active agent in this population and it benefits patients,” he adds. In Europe, Talon is exploring the potential of “authorization under exceptional circumstances” for Marqibo and plans to continue talks with the European Medicines Agency in the near future. Marqibo’s initial indication of relapsed and refractory adult ALL has an annual incidence of 3,200 cases in the U.S. and Europe. But Dr. Deitcher says Talon has a strategy to add indications in much larger disease categories, including front-line ALL, where the incidence is 9,200 cases a year, and front-line non-Hodgkin’s lymphoma, where the incidence is about 132,000 cases a year. These two markets currently represent worldwide sales of about $4 billion. Talon believes it could initially commercialize Marqibo in the U.S. for this orphan indication with a sales staff of around 10 people, because it already has strong relationships with most of the adult ALL physicians in the U.S., since most of them were part of the earlier clinical studies. Outside the U.S., the company’s preference is to partner Marqibo. “One of the advantages of not being strapped for financial resources is that we have no need to take a deal now when we know that, even months from now, the value of the deal would be greater,” Dr. Deitcher says. “So the deal with Warburg Pincus and Deerfield has allowed us to wait for the best deal.” Talon’s second major product is Menadione topical lotion, which recently completed a Phase 1 program and is poised to enter Phase 2 studies to address a painful and prominent skin rash caused by epidermal growth factor receptor (EGFR)-inhibitor oncology compounds such as Erbitux, Tarceva, Tykerb and Vectibix. Rash occurs in up to 90% of patients within weeks of treatment, leading to a dose adjustment or delayed treatment in about 70% of patients. Menadione’s goal is to be the first-in-class therapeutic to target the underlying cause of this rash. The key findings in the Phase 1 studies with healthy volunteers and cancer patients established an appropriate lotion strength and found no appreciable absorption into the bloodstream, which is “super important to the success of the therapeutic, the regulatory pathway and the development of the drug,” he points out. 
Besides planning for the Phase 2 program, Talon is also actively in talks to partner Menadione in order to move development forward as quickly as possible, Dr. Deitcher says. When asked if a collaboration would likely involve one of the companies whose drug causes the rash, he replied, “We have had and are in discussions with companies that have vested interests in the drugs that cause the rash as well as companies who don’t.” http://biotuesdays.com/2011/02/01/...accelerated-approval-of-marqibo/
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