Novartis has entered into a partnership with a group of non-profit and government organizations to develop the next generation of malaria drugs.

The company, which markets anti-malarial medication Coartem (artemether-lumefantrine), is working with the Wellcome Trust, a biomedical research charity in the UK; the Singapore Economic Development Board; and Medicines for Malaria Venture, a non-profit organization in Switzerland.

Paul Herrling, head of corporate research at Novartis and chair of the company's Institute for Tropical Diseases (NITD), noted that drug resistance is an inevitable obstacle to treating malaria over the long term -- and drug makers need to stay ahead.

"If we expect potential resistances to occur, now is the time to begin our research," he said.

Researchers sequenced the genome of the malaria parasite in 2002, and Novartis is now hoping to use these new findings in its drug discovery efforts. 

It's an effort that the company is pioneering. "In terms of the schematic, using this new genetic information, we are probably among the first," Herrling said.

NITD researchers are also hoping to find a common pathway that links two of the most serious forms of malaria: the deadly malaria tropica as well as malaria tertiana, which because of a tendency to recur can have significant social and economic costs.

Identifying that common pathway between the two malaria parasites --Plasmodium falciparum and Plasmodium vivax -- leaves open the possibility of developing one drug that can treat multiple forms of the disease. "This is the kind of thing that has become possible," Herrling said.

Unlike simpler viruses, the malaria parasite is less dependent on its human host for its basic survival. For this reason, researchers might some day be able to target parasitic proteins while sparing human proteins.

Elizabeth Winzeler, PhD, is one of the researchers working at the Genomics Institute of the Novartis Research Foundation and the Scripps Research Institute, performing a functional analysis of the parasitic genome.

"Many anti-malarial drugs act against targets that are also found in the human genome," she said, adding that the next generation of drugs could have fewer side effects.

Future malaria therapies are still five to ten years away from commercialization. Winzeler noted that researchers have only identified about the structure and function of about 40 percent of the parasite's proteins.

In addition to developing more targeted therapies, Herrling and Winzeler stressed the need for a single dose treatment -- as well as one that is cheaper to produce and easier to use in the field.

"The problem is not only the availability of drugs," Herrling said. "Even if drugs are arriving in the affected countries, [you have to make sure] the treatments reach the patients."

Novartis already provides Coartem at no profit in countries where malaria in endemic.

"We just need to keep new things in the pipeline," Winzeler said. "Pharmaceutical companies are the best places to do it because they have the infrastructure in place."

Articles

Studies of gene-based therapies being funded through public-private partnership

Novartis Developing Next Generation of Malaria Drugs

Generic drug maker Sandoz has received the regulatory go-ahead to market growth hormone Omnitrope, and its unprecedented application has ignited debate about whether the approval could open the door for biogenerics.

FDA, for its part, has refrained from calling Omnitrope a "biogeneric," instead preferring the term "follow-on protein." The difference is related to how the drug was approved as well as its "substitutability" at the pharmacy.

Sandoz, which is a division of Novartis, filed a new drug application for Omnitrope; the Office of Generic Drugs did not review the submission, according to Ajaz Hussain, Sandoz's vice president and global head of biopharmaceutical development.

Hussain, who was previously deputy director of FDA's Office of Pharmaceutical Science, noted that the company submitted details of its manufacturing operations as well as studies demonstrating safety, efficacy, and how the drug compares to Pfizer's Genotropin.

"What is different is that [Sandoz received additional] indications without having to do clinical trials in those populations," said Hussain, who described the company's submission as a "hybrid application."

He called FDA's decision a "precedent-setting approval," and noted that Sandoz expects to use this process for other drugs in its pipeline.

Yet not everyone agrees that the approval broke new ground.

Consulting firm Wood Mackenzie noted that Genotropin -- and only a handful of other biologics -- were approved under the Food, Drug, and Cosmetic Act (FDCA), which has a provision for generics. Most biologics were approved under the Public Health Services Act (PHSA), which does not.

"We believe the company has used Omnitrope as a bludgeon to force FDA and Congress into considering ways of approving generic versions of recombinant proteins approved under the PHSA legislation," the report stated. "Until such a pathway becomes available, which is unlikely to happen for several years yet, we believe recombinant protein drugs are safe from generic attack in the US."

Nevertheless, FDA's decision could expand the number of follow-on proteins on the market, according to Robert Bell, president of Drug and Biotechnology Development, a consulting firm. These products include insulin, peptides, calcitonin, and Interferon, which were also approved under the FDCA.

But he questioned whether these biogenerics would see the drastic price reduction that small molecule generics enjoy. Because of labeling differences, pharmacists can't substitute bio-similar Omnitrope for brand name Genotropin -- which means Sandoz must still detail the product.

"There should be a savings that should be passed on to consumers," Bell said. "Right now there's a very high barrier to entry."

Yet Hussain noted that, because biologics are more expensive to produce than small molecules, even a modest price reduction could make a big difference. "The cost savings are not going to be the same compared to small molecules but the dollar value saved can be very significant," he said.

The US has so far lagged behind Europe in establishing a process for approving biogenerics -- but both FDA, through its Critical Path Initiative, and members of Congress have prioritized the issue.

Approval of Omnitrope ignites debate on whether any precedent was set

Pharmaceutical Executive-06-21-2006

Novartis Developing Next Generation of Malaria Drugs

Sandoz Brings Test Case for Biogenerics