Designing novel delivery vehicles for off-patent molecules looks like a growing trend among Indian drug makers as therapeutics of ‘minimum toxicity with maximum efficacy’ turn increasingly vogue in the global marketplace.

In January, Dabur Pharma launched a nanoscale drug delivery system (NDDS) for paclitaxel in India. This anti-cancer drug has been implicated in some undesirable side effects, largely owing to cremophor — a castor oil-based solvent used in its formulations. Dabur’s Nanoxel claims to cut this risk as it is cremophor free. Besides, polymeric nanoparticle drug delivery systems enable therapy to take a preferential course to the cancerous cells, thereby throwing open a larger window for anti-tumor activity, the company added.

Specializing in delivery technologies for micellar delivery of hydrophobic drugs, this oncology firm is currently in late-stage clinical development of a peptide-based drug for gastrointestinal carcinomas. Liposomal drug delivery using biodegradable lipids is another area Dabur is keen on.

New Delhi-based Dabur expects to take Nanoxel to regulated markets in coming years. In the U.S., it may compete with Abraxis Bio’s Abraxane, which uses human albumin for paclitaxel delivery. “While the efficacy of both products are comparable in terms of response rate, Nanoxel has been shown to be safer than Abraxane in terms of incidence of neuropathy, which is known dose limiting and cumulative toxicity of paclitaxel,” said sources from Dabur.

Nano-enabled systems present a great promise as they are fast replacing polymer therapeutics. Growing at the rate of 37%, they are set to touch $26 billion by 2012 from the present $3.39 billion, predicts a report from Cientifica Ltd.

Competitive Edge

If Dabur’s is a breakthrough in nano delivery, Ranbaxy was the first to develop a platform technology for once-a-day ciproflaxacin pills. Ranbaxy sold the formulation technology rights to Bayer AG, maker of Cipro, in a multi-million dollar deal in September 1999. Focusing mainly in the oral NDDS space, Ranbaxy has already developed gastro retentive, modified matrix, multiparticulate and aerogel platform technologies. More than 45 products from these four streams contribute 8.8% of the company’s total earnings.

“We are focusing heavily in this area. NDDS drugs will continue to gain importance, as these formulations are patient friendly and represent an immense opportunity for the pharma companies to sharpen their competitive edge in an increasingly crowded market,” said a Ranbaxy spokesperson. Ranbaxy also has a pact on fast-melt technology with Ethypharm of France.

Lately, Alembic Limited reached a licensing agreement with UCB of Belgium on novel delivery technology for levetiracetam extended release tablets (Keppra XR). This mid-sized firm from western India would receive milestone payments of $11 million and future royalties. The once daily anti-epileptic is in late Phase III and trial results are expected in the fourth quarter of 2007.

Other majors in the field include Biocon, Cipla, Lupin and Panacea Biotec. While Biocon’s oral insulin pills just crossed Phase I, Cipla is reportedly working on an inhalable version of the hormone. Lupin is known for once-a-day ceph formulations. The company focuses on injectables and pulmonary systems too. Themis Medicare, a mid-level NDDS player from Mumbai, is designing formulations of clear gels and injectables for lipophilic compounds. Acyclofenac ready-to-use injection is the latest addition in Themis’ kitty.

Dr Reddy’s Lab’s $11 million buy-out Trigenesis in 2004 gave it an NDDS angle. Trigenesis brought along a range of proprietary drug delivery technologies for dermatological products.

Lower Risks, Higher Success

Overseas drug delivery companies also form part of India’s NDDS landscape. Ethypharm and Nektar Therapeutics have set up shops in Indian cities to leverage the fast-growing skill base in this field. “More companies would take to this area given the large talent pool here,” stated an official from Nektar India. The U.S. drug delivery major is behind the groundbreaking technologies of PEG-Interferon Alpha-2A (Pegasys, Roche), PEG-filgrastim (Neulasta, Amgen) and inhalable insulin (Exubera, Pfizer).

Clearly, new formulations and routes for drug delivery have the potential to broaden the therapeutic potential of administered treatments. Not so surprisingly, the emerging promise has attracted quite a few Indian firms to the NDDS space. Reduced risk, capital investment and time are the other key factors being pointed out for this rising interest.

NDDS research has limited risk because most of the inherent properties of molecules, including efficacy, are likely to have been already established for drugs evaluated for an NDDS platform. This is a significant upside, explained Ajay K. Vij, Dabur Pharma’s chief executive officer. “There is a high probability of success for NDDS research compared to NCE, where the high level of uncertainties and risk about the commercial potential continue until the product is successfully launched.”

Though exact figures are not available, several Indian firms are presently involving a big chunk of their R&D resources and manpower on delivery research. Are they seeing a fairly bigger slice of $75 billion global NDDS pie up for grabs?

S. Harachand is a pharmaceutical journalist based in Mumbai.