by Robert Galbraith

ROME, June 26 (APM) - Innovative drugs coming onto the market are already testing drug approval processes but the real challenge will be the next generation of therapies and regulators need to start planning now for more complex decision-making, according to the head of the Italian medicines agency AIFA.

Speaking at the annual congress of the Italian industry body Farmindustria in Rome, Mario Melazzini highlighted the growing difficulties in having affordable innovative drugs for health systems and sustainable R&D processes for pharma.

He noted that new drugs are often discovered by small companies which are then snapped up by big groups in huge, often speculative investments. Some of them are for drugs which have been in development for 10 years. The benefits of using the drugs, including avoided future health costs, may not become apparent for some time.

"That means we need medium to long-term planning," Melazzini said during a roundtable discussion at the industry congress on Wednesday. "For hepatitis C drugs, for example, we need to look 10-15 years ahead to assess the avoided healthcare costs, direct and indirect, and the welfare savings that will be gained in the future."

Advanced therapies on the market now, three of which were developed in Italy, exemplify the difficulties in making successful therapies available at affordable costs, the AIFA chief said. Often they are 'one shot' therapies, meaning that the patients' condition or genetic defect is resolved with just one treatment, he pointed out.

Melazzini highlighted the differences between GlaxoSmithKline's Strimvelis and uniQure's Glybera, although he did not mention either of the therapies by name.

Strimvelis is a treatment for severe combined immunodeficiency due to adenosine deaminase deficiency (ADA-SCID). Italy approved reimbursement of the therapy in August 2016 (APMHE 49009). According to Melazzini, it will be used to treat just two or three children a year in Italy and perhaps 20 in Europe as a whole.

Glybera (alipogene tiparvovec) was approved as a treatment for a small subset of patients with familial lipoprotein lipase deficiency (LPLD), an ultra-rare genetic disorder, in 2012. It had a price tag of $1 million. In April this year, uniQure announced it would not be seeking to renew the marketing authorisation because of the very limited prospects of it being used (APMHE 52751).

The decision was not to do with the efficacy of the treatment but because it was not considered to be viable commercially, Melazzini said. "Finding the right approach, the right balance, is the challenge we will be faced with more and more as new innovative therapies are developed," he predicted.

Melazzini cited early approval decisions as another important area for regulators in the future because of the huge sums of money involved. "We will have to ask complex questions about companies and their increasingly rapid R&D processes in regulatory decisions about whether to fast track new therapies," he said.

He cited the example of Eli Lilly's solanezumab, a drug which had promised to end the long wait for an effective treatment for Alzheimer's disease. Melazzini described the data from the Phase II trial as "extremely positive", prompting the question of whether early approval might be granted. "But the FDA said it wanted a Phase III trial as well and so the company did Phase III. Unfortunately, it was a failure," Melazzini noted.

An article in the New England Journal of Medicine in May calculated that the FDA saved taxpayers many billions of dollars by its decision not to fast-track. Melazzini pointed out that the company says it lost billions of dollars of investment as result of the failure, and he stressed that its research was in an area crying out for effective therapies.

The head of Farmindustria Massimo Scaccabarozzi, who was part of the same roundtable discussion, also referred to the study. On a recent visit to Lilly, he was told that the staff were in tears after hearing the news about the Phase III trial. "The staff, not the investors, were crying," he said.

Scaccabarozzi cited another view of the trial failure: "Just as well it didn't work because we wouldn't have been able to afford it anyway." He described this as a denial of science and the need to progress. It would be much better for everyone if an effective therapy to treat Alzheimer's disease is developed, he said.

/rg/clg