New drug olaparib offers hope to women with genetic breast cancer

A new drug for genetic breast cancer could help thousands of women with hereditary forms of the disease, the first tests on patients suggest.

A study involving 54 women with advanced genetic breast cancer found that the drug olaparib could stop the growth of tumours, and shrink them in more than 40 per cent of cases.

In one case, a woman's tumour disappeared completely after treatment with the drug, according to results to be presented at a science conference today.

About 5 per cent of the 46,000 cases of breast cancer in Britain each year are caused by defects on the BRCA-1 and BRCA-2 genes, which put women at much higher risk of developing aggressive cancers of the breast or ovaries.

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Many women who test positive for the mutations have their breasts removed as a precaution, as they have an 80 per cent risk of developing breast cancer in their lifetime.

Olaparib, made by AstraZeneca , is the first of a new class of drugs specifically designed to treat BRCA-related cancers to be tested on patients. If further tests are successful, they could be used at an early stage to treat or prevent disease occurring within affected families, scientists say.

Pharmaceutical companies are also due to present targeted therapies for cancers of the lung, stomach and ovaries this week at the American Society of Clinical Oncology conference in Orlando, Florida, the world's largest gathering of cancer scientists.

Andrew Tutt, director of the Breakthrough Breast Cancer Research Unit at King's College London, who led the trial, said that the results for olaparib were "very promising".

"We are hopeful that olaparib could provide a targeted treatment for women with BRCA-related breast cancer," he said. "Some women also develop breast cancer before they know they are carrying the gene, or see it recur if they have been diagnosed previously."

Charlotte Sword, 40, has had breast cancer diagnosed twice, because of the potentially deadly mutation to the BRCA-1 gene which runs in her family. Her younger sister Audrey has suffered it three times. Both women have had double mastectomies and their ovaries removed.

"Breast cancer has left a horrific mark on our family due to a mutation being passed down the paternal line", Mrs Sword said yesterday. "I have three nieces who could benefit from this treatment, and could be spared the dreadful illness and side-effects of treatment that my sister and I had to go through."

Olaparib works by blocking a protein that makes cancer cells which have a BRCA fault unable to repair their own DNNA. This causes the cancer cell to die and means that the tumour should either stop growing or get smaller.

Because the drug works in a targeted way, it kills cancer cells while leaving healthy cells alone in a way that chemotherapy does not, which could help to reduce the punishing side-effects of cancer treatment.

In the study carried out at hospitals in Britain, Europe, the US and Australia, 27 patients took 100mg oral doses of olaparib while another 27 took 400mg doses. More than 40 per cent of tumours in the higher dose group reduced significantly in size, while all tumours were prevented from progressing for an average of six months.

The Times reported this year that the London community of Ashkenazi Jews is being offered screening for BRCA genes that raise risks of breast, ovarian and prostate cancers. Ashkenazi have a high incidence of BRCA-related breast cancer.

The NHS currently offers BRCA testing, but only for women whose relatives have had cancer because of the mutations. But up to 50 per cent of people with the faulty genes do not have a family history of the diseases, largely because the gene can be carried by men.

Dr Tutt said that orlaparib may also have potential as an early-stage or preventative treatment. He added: "It is important to remember this drug is at a very early stage of development." Herbie Newell, Cancer Research UK scientist at the Northern Research Institute, Newcastle University, said he was "extremely encouraged" by the study's results.

He said: "Olaparib is one of a family of targeted therapies currently in clinical trials and Cancer Research UK expect that this new class of anti-cancer treatments will make a significant impact in the fight against cancer."

In the family

8% Proportion of cases of breast cancer in women thought to be triggered by genetic factors, although many of the exact causes remain a mystery

2,000 Number of breast cancer cases a year (5 per cent of the total) known to be caused by changes in either the BRCA-1 or BRCA-2 genes that were the first to be associated with a much higher risk of developing breast cancer

1 in 800 Proportion of women in whom a faulty BRCA-1 gene is present. One in 500 carries a faulty copy of the BRCA-2 gene

50-80% Chances of a woman with these genes of getting breast cancer in their lifetime, up to seven times higher than those who do not carry the mutations. They also have a 60 per cent increased risk of ovarian cancer

Sources: Cancer Research UK; Times database

Pharma firms continue to face patent violation charges in Europe
8 Jun 2009, 0122 hrs IST, Rupali Mukherjee, TNN

NEW DELHI: Even after India raised concerns with EU, troubles of generic companies which export drugs to developing countries through Europe are far from over as seizures by Dutch customs still continue.

In yet another case, a shipment of popular antibiotic, Amoxicillin was seized in Frankfurt recently. The drugs manufactured by domestic company Medopharm were shipped to Republic of Vanuatu, an island nation in the Pacific Ocean, through Frankfurt.

In this recent case, customs authorities seized a shipment of 3,047,000 pills (quantity equivalent to 76,000 courses of treatment) of Amoxicillin (250 mg) worth 25,000 euros, for almost a month before releasing it. Sources said that the consignment was detained on grounds of suspected trademark infringement.

Experts pointed out that there was no valid reason for detaining these medicines especially since the name ‘Amoxicillin' is an international non-proprietary name. This seizure is the latest in a long list of cases that demonstrate that EU regulations are actively hampering access to medicines to developing countries. In 2008, there were 16 similar cases of seizures of medicines shipped from India in the Netherlands. (Other recent seizures include those of medicines from Dr Reddy's and Ind-Swift.)

When this particular shipment came into Germany, customs noted that the medicines packed are of the same type as the drugs that GlaxoSmithKline in UK has copyrights for, according to an industry source. German customs authorities then informed the company, and gave them a sample of drugs for inspection. The consignment was later cleared and sent to the final destination.

These seizures have been driven by an EU regulation on border measures that has empowered customs officials to interfere in legitimate trade of generic medicines, a statement from Health Action Network says.

DG Shah, secretary general of Indian Pharmaceutical Alliance says "The EU member states continue to abuse Regulation 1383 of 2003 to create barriers and harass legitimate trade in generics. It is time that the government steps in and takes effective steps to protect India's exports of pharmaceuticals". Customs is incompetent to interpret IPRs and should not be entrusted to enforce the same, he added.

The issue has been raised by India at the TRIPS (Trade-related aspects of Intellectual Property Rights) council meeting in February, and thereafter when the Dutch trade minister was on a visit here. Experts pointed out that earlier international public health and consumer groups have raised the issue with World Health Organization (WHO) and the World Trade Organization (WTO) voicing their concerns over seizures by Dutch customs authorities of Indian generic drugs shipped through the Netherlands en route to Brazil, Colombia and Peru.

According to manufacturers, all products were ‘‘legitimate generics'' and did not violate any patent rights in the exporting or the importing countries.

Sanofi Aventis will pay Pfizer €30m ($41m) for a former Exubera manufacturing plant in Frankfurt-Höchst, Germany that was due to be bought by inhaled insulin specialist MannKind.

The French drugmaker said the facility, one of the largest of its kind in the world, will produce its Lantus SoloStar (insulin glargine) diabetes treatment, sales of which increased nearly 28 per cent to $2.45bn (€1.75bn) last year.

Pfizer, which has been seeking to sell the plant for several years following the market failure of its inhaled insulin product Exubera, agreed a sale with California, US-based MannKind in March.

The deal hinged on MannKind gaining manufacturing approval from operator Infraserv and, crucially, approval by Pfizer's original Exubera co-developer Sanofi, which retained a "right of first refusal" option on the plant.

Evidently, gains made by Lantus in the SoloStar pen format coupled with growing worldwide demand for diabetes treatments, the World Health Organization predicts that more than 350m will develop the condition by 2030, convinced Sanofi to exercise its option.

In a press statement Martin Stewart, general manager of Sanofi in Germany, said: "The strong increase in demand for our insulins, and especially Lantus, drives us to considerably extend our production capacities.

"In combining the acquired Diabel site with our existing plants Sanofi-Aventis will operate the largest insulin capacity in the world in Frankfurt," Stewart continued.

The acquisition fits with Sanofi's ongoing efforts to "double Lantus sales by 2012." In April, the firm said it that it will invest $90m (64m) over the next three years to boost Lantus manufacturing capacity in China.

One small setback for MannKind?

According to some observers MannKind, which is yet to issue a statement on the Sanofi deal, may be less disappointed about the "loss" of the plant itself than it is about the regulatory benefits the acquisition would have provided.

When MannKind signed its original acquisition deal with Pfizer in March, Rodman & Renshaw analyst Jason Butler said that the manufacturing capacity provided by the facility was not the key motivation for the deal.

Instead, he suggested that the insulin inventory MannKind was due to gain and the license to make insulin for pulmonary delivery that it was required to obtain under the original terms would be of more benefit for MannKind.

If this reading of the situation is accurate, the fact MannKind still obtains EUR3m worth of insulin regardless of the Sanofi deal, will be seen as positive for the US firm.

Positive Ph III Afresa data boosts share price

The response to data from the latest Afresa trials reported at this year's American Diabetes Association's scientific sessions is also likely to boost MannKind's spirits and alleviate any lingering disappointment.

Results from a two-year Phase III study showed that there is no difference in forced expiratory volumes (FEV) between patients treated with Afresca compared with standard insulin.

The news saw MannKind's share price climb 15 per cent to a 52-week high of $8.12 in trading on the New York Stock Exchange late last week.