October 10, 2014

Reformulations provide a jump start on clinical development.

Started in 2013 as Voltarra Pharmaceuticals, Levolta aims to fast-track drug development using reformulations to overcome hurdles and rapidly bring products to market.

Time is money in the pharmaceutical industry, where setbacks can easily delay the process and quickly drive up the price of a t. All too often, R&D for a promising compound hits an impasse and fails in clinical trials or does not gain approval from the US Food and Drug Administration (FDA), causing companies to absorb the costs associated with product development. Failed drug trials cost billions of dollars for pharmaceutical companies in the United States alone.

Under the guidance of CEO Richard Becker, Levolta Pharmaceuticals reformulates late-stage assets to address issues such as side effects and safety concerns. As the company’s name implies, Levolta jump-starts a drug’s chances of success by providing an enhanced therapeutic index and reducing product development time- lines by 8–10 years.

“We are coming in more than mid-stream, and we can do a small phase 2 trial to establish proof of concept. Then we can go right to phase 3,” said Becker, who has 20 years of pharmaceutical leadership experience in companies such as Bayer, BASF, Novartis and Merck. “If you reformulate a marketed compound, you already have the safety and the FDA approvals, so the hurdles are not as high.” Levolta’s business model is lightning quick in the pharmaceutical world, in which it can take upward of 10 years for a drug to obtain the approvals needed to be marketable.

The company features a portfolio of early stage small molecules and late-stage new clinical com- pounds for rheumatology, the central nervous system, oncology and immunology, which Levolta obtained through the 2013 merger of two companies. The first was IMC Biotechnology, which brought Renee Stewart on board as Levolta’s CSO. Stewart is formerly the CEO of IMC and has many years of experience in both research and medical labs. IMC’s assets included new spleen tyrosine kinase and oral tumor necrosis factor inhibitors, which are both currently in early pre-clinical development for treating inflammatory diseases such as rheumatoid arthritis. Levolta is seeking partners for moving these promising compounds forward.

The second company was Renascense Pharmaceuticals, which brought with it the company’s former CEO, Ketan Desai. Now Levolta’s chief medical officer, Desai has 17 years of clinical, regulatory and medical affairs experience, as well as intellectual property in the form of US and international patents. Currently, Desai is working on two late-stage compounds that he reformulated: VOLT01 for the prescription market to treat osteoarthritis and VOLT03 as an over-the-counter curcumin nutraceutical.

VOLT03, an enhanced curcumin with superior anti-inflammator y proper ties, is ready to be launched. Curcumin is currently in clinical trials for treating patients with inflammation, cancer and auto-immune disorders. Recent data from the Nutrition Business Journal puts curcumin in the top 10 best-selling supplements in the United States, estimating that consumer sales hit $80 million in 2011 and are expected to grow 21.5% to $235 million from 2013 to 20161. The total US dietary supplement market of curcumin is estimated at several hundred tons. The Levolta team is banking on the sales of VOLT03 to help support the final approval stages for VOLT01, which is a derivative of zoledronic acid used to treat osteoarthritis.

Targeting osteoarthritis

According to the World Health Organization, by 2020 osteoarthritis will be the leading cause of disability worldwide. Meanwhile, the US Centers for Disease Control and Prevention reports that osteoarthritis affects 26.9 million adults in the United States with total costs of $21.1 billion.

Novartis’ Reclast, a zoledronic acid–based drug, is used to treat osteoporosis, Paget’s disease and bone cancers to the tune of roughly $1.6 billion in 2012. But there are unpleasant side effects including: flushing, fever, joint and muscle pain, and necrosis of the jaw. Desai reformulated the compound, ameliorating the side effects while improving its efficacy, solubility and safety. “In a randomized phase 2a trial, VOLT01 has demonstrated statistically significant improvements in safety and efficacy in controlling knee osteoarthritis compared to zoledronic acid alone, with the added benefit of no post-dosing symptoms,” Desai said. “VOLT01 has the potential to be the first disease-modifying drug for osteoarthritis, and its approval would be a new application for zoledronic acid.” Desai will present the phase 2a study as a poster presentation at the American College of Rheumatology’s upcoming annual meeting.

In early 2014, researchers at the Menzies Research Institute at the University of Tasmania had begun a phase 3 randomized trial involving Reclast versus placebo when they heard about VOLT01 from Desai. Intrigued, study director Graeme Jones invited Levolta to join the clinical trial. He got unanimous approvals from the study sites and regulatory agency to add another arm to the study to test if VOLT01’s reported superior efficacy and safety results against Reclast in a head-to-head phase 3 trial for knee osteoarthritis. This multicenter trial is a randomized, placebo-controlled, double-blind clinical trial under the auspices of Medicines Australia. It will take a little over two years to complete.

“Entering a phase 3 registration trial is an important milestone for VOLT01,” Becker said. “We expect that interim study data will be avail- able in the second half of 2015 and strongly believe that data analysis at that point will sup- port expansion of the clinical trial in the US and globally. We also anticipate applying for a new drug application (NDA) with the Therapeutic Goods Administration in 2017.”

Another major milestone was achieved in September when the United States Patent and Trademark Office approved VOLT01’s patent application entitled CO-ADMINISTRATION OF STEROIDS AND ZOLEDRONIC ACID TO PREVENT AND TREAT OSTEOARTHRITIS.

Diversified portfolio

By joining forces, Becker, Desai and Stewart each bring different expertise and assets to Levolta’s business model. This diversity also reflects the company’s varied product pipeline. Levolta currently has a portfolio of five products, which are in various stages of development. In addition to VOLT01, there are the new early stage small molecule spleen tyrosine kinase and oral tumor necrosis factor inhibitors and VOLT03, the nutraceutical curcumin. Levolta is also develop- ing VOLT02, a reformulated progesterone product to treat brain traumas, with other potential applications relating to women’s health still to be investigated.

“I think there is much more customer value when you have a portfolio approach,” Becker said. “You attract different investors and custom- ers when there are different compounds at different stages of development.” As 2014 draws to a close, Becker, Stewart and Desai look forward to building Levolta’s track record of successful reformulations of compounds and positive results for the early stage products the company is testing.

References

1. Jägar R et al. Nutrition Journal, 13:11(2014)

CONTACT DETAILS

Richard Becker, CEO
Levolta Pharmaceuticals Inc. Bethlehem, Pennsylvania
Tel: + 1 848 702 0682
Email: [email protected]