January 3, 2014

Newco Levolta Pharmaceuticals (formerly Voltarra Pharmaceuticals) Teams With Asia-Pacific Researchers On Zoledronic Acid For Osteoarthritis

By Joseph Haas
The Pink Sheet, January 3, 2014

Executive Summary

Pennsylvania-based Levolta has a combination product that includes a reformulated version of zoledronic acid ready to move into Phase III in osteoarthritis, but the program will move forward first in the Asia-Pacifc region, with U.S. and EU development intended down the road.

It’s not ready to reveal all its secrets just yet, but new company Levolta Pharmaceuticals Inc. believes it has a winner with a combination product that includes a reformulation of zoledronic acid (Novartis AG‘s Reclast) for osteoarthritis.

Based in Bethlehem, Pa., Levolta combines the vision of three executives and two former small companies, IMC Biotechnology, also based in Pennsylvania’s Lehigh Valley, and Renascense Pharmaceuticals, an unincorporated outfit built around zoledronic acid’s potential for treating osteoarthritis if only the compound’s post-dosing effects could be ameliorated. CEO Richard Becker, a former exec at Alcon Inc.Merck & Co. Inc., Novartis and other biopharma firms, brought the two companies together under the new name, unveiling Levolta in November at the Pennsylvania chapter of BIO’s Life Sciences Future meeting (“People In The News: Topside Changes At Oxygen Biotherapeutics, EMD Serono And Volatarr; CMS’s Shrank Lands At CVS Caremark” – “The Pink Sheet,” Dec. 2, 2013).

In addition to its combination drug for osteoarthritis, about to enter Phase III as VOLT01, Levolta comprises Renascense’s re-formulated versions of progesterone for traumatic brain injury (VOLT02, now in Phase II) and complex curcumin for oncology and autoimmune disorders. Former Renascense CEO Ketan Desai joins Voltarra as its chief medical officer, while IMC’s former CEO Renee Stewart, comes aboard as chief science officer. In addition, IMC contributes a portfolio of preclinical spleen tyrosine kinase (SYK) and tumor necrosis factor (TNF) compounds to the Levolta pipeline.

For now, while Levolta goes about raising initial funding beyond that contributed by the three principals and other small investors, the focus is on VOLT01, a conjugated zoledronic acid combined with a novel compound that Becker would not specify because intellectual property rights are still being finalized. He would say, however, that the unnamed compound helped produce a superior therapeutic index compared to zoledronic acid alone in a Phase II trial in patients with osteoarthritis of the knee.

At the November state BIO meeting, Levolta unveiled data from a Phase II 20-patient study showing that VOLT01 eliminated the post-dosing syndrome typically seen with Reclast, while also producing stronger efficacy as measured by change in pain as rated in a 100 mm visual analogue score over six months of treatment. That presentation led to a communication that put VOLT01 on a path into Phase III study, albeit in Asia-Pacific. While Levolta aspires to develop VOLT01 in the U.S. and Europe, it is proceeding for now with its program in Asia-Pacific for economic reasons.

“We were contacted by a very prominent Asia-Pacific-based research organization that has developed bisphosphonates, namely ZA, in osteoarthritis,” Becker said in an interview. “Given that our efficacy data were in knee osteoarthritis, which is a very difficult indication to address, once they saw our data, they solicited our interest in joining their ongoing Phase III study” comparing Reclast to placebo. Once an agreement is finalized, the partner, which Becker would describe only as an academic institution, will initiate a third arm of the trial to compare ZA, the Levolta candidate and placebo in osteoarthritis patients.

Existing Data Backed Theory

The effort benefited from the fact that there already were trial data in the literature showing that zoledronic acid is effective in osteoarthritis (“Zoledronic Acid Relieves Knee OA Pain And Shrinks Bone Marrow Lesions” – Health News Daily, Jun. 17, 2011). Becker estimated that the drug is used widely off-label in that indication in the U.S. and EU. Levolta studied the compound in the dosages approved by FDA for the branded Reclast product.

The hold-up in getting the drug approved in osteoarthritis had been a high rate of post-dose effects – which can include flushing, fever, joint pains and muscle aches. An estimated 44% of patients who take the drug incur one or more of these side effects. In addition, a smaller percentage faces the risk of developing osteonecrosis of the jaw.

Desai, who was head of rheumatology at Aventis Pharma Ltd. in addition to holding clinical development positions at SmithKline BeechamBiothera and Neose Technologies Inc., began by doing his own re-formulation work and supplied his formulation to a clinical trial. He expected to see a better safety profile, Becker explained, but was pleasantly surprised when his version also showed better efficacy results.

Becker’s near-term plan is too seek grant funding and angel investments for Levolta, while it functions as a virtual company with the three executives. While VOLT01 is being tested in Asia-Pacific, that configuration is workable but Becker admits the firm will need to build critical mass when it hopes to move the compound in U.S. and/or EU development, even if it contracts much of the work out. For now, he thinks the company is not far along enough to seek venture capital or investment banker backing.

The longer-term plan is to find a commercialization partner for VOLT01 in Asia-Pacific and then likely co-development and commercialization partners for the U.S. and EU, he added. Then, in addition to the progesterone and curcumin programs, Levolta also plans to test the IMC SYK and TNF compounds in oncology and immunology indications.

But Becker also is looking to expand the new company’s portfolio, with potential in-licensing deals focusing on early-stage clinical development programs in targeted therapeutic areas. “I’m a big believer in obtaining assets already in clinical development,” he said. “We’re looking externally at rheumatology, immunology and oncology assets; those are the spaces that we want to play in. We’re now talking to post-IND companies that have Phase I data and I think we’ll collaborate down the road.”