genglob magazine » GENERICS

NATCO confirms filing of ANDA for Generic Revlimid

admin — Fri, 03 Sep 2010 22:44:27 +0000

Hyderabad based NATCO Pharma Limited today confirmed that the company has filed an Abbreviated New Drug Application (ANDA) with the U.S. Food and Drug Administration (FDA) seeking approval to market lenalidomide capsules in 5, 10, 15 and 25mg strengths prior to the expiration of various U.S. patents. NATCO’s lenalidomide capsules are the generic version of Celgene Corporation’s Revlimid®.

On August 30, 2010, pursuant to the Hatch-Waxman Act, NATCO notified Celgene that its ANDA requesting approval from the FDA for a generic version of Revlimid® contained a paragraph IV certification asserting that various Revlimid® patents are invalid, unenforceable and/or not infringed. Lenalidomide, which is presently marketed as Revlimid by Celgene, is a derivative of thalidomide and is used in the treatment for multiple myeloma. Lenalidomide has also shown efficacy in the class of hematological disorders known as myelodysplastic syndromes (MDS).

NATCO believes it may be a “first applicant” to file an ANDA for the 25 mg generic version of Revlimid® and, should its ANDA be approved, may be entitled to 180 days of generic market exclusivity for that strength.

The market size of Revlimid in the USA is estimated to be around US $ 1.5 Billion, growing at 44% compared to last year.

Breast Cancer Gene Patents Struck Down

admin — Tue, 30 Mar 2010 23:02:27 +0000

A biotechnology company that holds patents on the BRCA1 and BRCA2 genes may lose them after a federal judge ruled that seven of their 23 patents involving the genes tied to breast and ovarian cancers should not have been granted, the New York Times reports. The American Civil Liberties Union and the Public Patent Foundation filed a suit last year, claiming that patents held by Myriad Genetics kept competitors from creating tests to find mutations in the genes and stifled research.If the court’s decision is upheld, the biotechnology industry would “have to get more creative about how to retain exclusivity and attract capital in the face of potentially weaker patent protection,” said Kenneth Chahine, who filed an amicus brief for Myriad, the Times reports.

A federal judge on Monday struck down patents on two genes linked to breast and ovarian cancer. The decision, if upheld, could throw into doubt the patents covering thousands of human genes and reshape the law of intellectual property.

United States District Court Judge Robert W. Sweet issued the 152-page decision, which invalidated seven patents related to the genes BRCA1 and BRCA2, whose mutations have been associated with cancer.

The American Civil Liberties Union and the Public Patent Foundation at the Benjamin N. Cardozo School of Law in New York joined with individual patients and medical organizations to challenge the patents last May: they argued that genes, products of nature, fall outside of the realm of things that can be patented. The patents, they argued, stifle research and innovation and limit testing options.

Myriad Genetics, the company that holds the patents with the University of Utah Research Foundation, asked the court to dismiss the case, claiming that the work of isolating the DNA from the body transforms it and makes it patentable. Such patents, it said, have been granted for decades; the Supreme Court upheld patents on living organisms in 1980. In fact, many in the patent field had predicted the courts would throw out the suit.

Judge Sweet, however, ruled that the patents were “improperly granted” because they involved a “law of nature.” He said that many critics of gene patents considered the idea that isolating a gene made it patentable “a ‘lawyer’s trick’ that circumvents the prohibition on the direct patenting of the DNA in our bodies but which, in practice, reaches the same result.”

The case could have far-reaching implications. About 20 percent of human genes have been patented, and multibillion-dollar industries have been built atop the intellectual property rights that the patents grant.

“If a decision like this were upheld, it would have a pretty significant impact on the future of medicine,” said Kenneth Chahine, a visiting law professor at the University of Utah who filed an amicus brief on the side of Myriad. He said that medicine was becoming more personalized, with genetic tests used not only to diagnose diseases but to determine which medicine was best for which patient.

Mr. Chahine, who once ran a biotechnology company, said the decision could also make it harder for young companies to raise money from investors. “The industry is going to have to get more creative about how to retain exclusivity and attract capital in the face of potentially weaker patent protection,” he said.

Edward Reines, a patent lawyer who represents biotechnology firms but was not involved in the case, said loss of patent protection could diminish the incentives for genetic research.

“The genetic tools to solve the major health problems of our time have not been found yet,” said Mr. Reines, who is with the Silicon Valley office of the firm Weil, Gotshal & Manges. “These are the discoveries we want to motivate by providing incentives to all the researchers out there.”

The lawsuit also challenged the patents on First Amendment grounds, but Judge Sweet ruled that because the issues in the case could be decided within patent law, the constitutional question need not be decided.

The decision is likely to be appealed. Representatives of Myriad did not return calls seeking comment. But this month, the company’s chief executive, Peter Meldrum, told investors that “regardless of the outcome of this particular lawsuit, it will not have a material adverse effect on the company,” or its future revenues, according to the Pharmacogenomics Reporter, “or on the future revenues of our products.”

Myriad sells a test costing more than $3,000 that looks for mutations in the two genes to determine if a woman is at a high risk of getting breast cancer and ovarian cancer. Plaintiffs in the case had said Myriad’s monopoly on the test, conferred by the gene patents, kept prices high and prevented women from getting a confirmatory test from another laboratory.

Janice Oh, a spokeswoman for the United States attorney’s office in Manhattan, which represented the Patent and Trademark Office in the case, had no comment.

One of the individual plaintiffs in the suit, Genae Girard, who has breast cancer and has been tested for ovarian cancer, applauded the decision as “a big turning point for all women in the country that may have breast cancer that runs in their family.” Chris Hansen, an A.C.L.U. staff lawyer, said: “The human genome, like the structure of blood, air or water, was discovered, not created. There is an endless amount of information on genes that begs for further discovery, and gene patents put up unacceptable barriers to the free exchange of ideas.”

Bryan Roberts, a prominent Silicon Valley venture capitalist, said the decision could push more work aimed at discovering genes and diagnostic tests to universities. “The government is going to become the funder for content discovery because it’s going to be very hard to justify it outside of academia.”

John Ball, executive vice president of the American Society for Clinical Pathology, one of the plaintiffs in the case, called the decision “a big deal.”

“It’s good for patients and patient care, it’s good for science and scientists,” he said. “It really opens up things.”

sales of generics continue to climb

admin — Wed, 03 Mar 2010 12:34:50 +0000

THE GLOBAL generic drug industry has witnessed an almost decade-long sales euphoria and volumes and sales growth of prescription generic drugs continued to increase in 2009.

In the 12 months ended September 2009, global prescription sales growth of generic drugs climbed by 7.7%, up from 3.6% in 2008, according to US-based health care information and consulting company IMS Health. This compares with the 5.7% growth seen within the overall global pharmaceutical universe last year, says Doug Long, vice-president, industry relations at IMS Health.

During that 12-month period, global generic products generated $83bn (€59.8bn) in audited sales, according to IMS. US market data provider BCC Research estimates that the global market was worth $84bn in 2009.

The global industry virtually had 10 years in a row of good growth – not only in prescriptions but also in sales. All the dynamics of the generics industry were strong and it seems to have even prospered more during the economic slowdown. Generics now account for 72% of the total US pharmaceutical market volume, reaching an all-time high in 2009, he adds. However, they still only account for 17% of total sales, despite generics sales having more than tripled since 2000. In the 12 months ended November 2009, the US generics market was valued by IMS at $31bn. BCC Research estimates the US market in 2009 at $34bn.

The demand for generics is increasing steadily because of pressure to control health care costs. But at the same time, fierce price competition is resulting in slashed profit margins for participating companies. A major growth driver for the generics sector is that several blockbuster pharmaceutical brands are coming off patent and therefore open to generic competition.

Israel-based Teva Pharmaceutical Industries’ (18% global market share), Switzerland-headquartered Novartis’s US generics business, Sandoz (10%), and both US-based Mylan (6%), and Watson (6%) are leading generics manufacturers, already occupying 40% of the global market. IMS estimates that sales from the top 10 US generic players grew at an average of 13.2% last year.

AT THE TOP

The top four global generics manufacturers – Teva, Sandoz, Mylan and Watson – also accounted for 47% of the US market as of 2009, according to IMS. The top 10, which also includes Canada’s Apotex, Pfizer’s US-based generics business Greenstone, Qualitest Products, Mallinckrodt and Actavis US, all US, and Lupin Pharmaceuticals, the US subsidiary of India-based Lupin, accounted for 66% of the market.

This means there are still many players out there that are pretty small and would be ripe for acquisitions or mergers. Everybody expects that there will be consolidation within the generic drugs industry as smaller producers are experiencing significant margin pressure in this environment.

At the same time, large companies are consolidating their operations in established markets and/or expanding into emerging ones through local acquisitions or partnerships.

In May 2009, Sandoz acquired the specialty generics business of Austria-based Ebewe Pharma, while Teva closed its acquisition of US-based Barr Pharmaceuticals in December 2008.

In December, Teva’s Japanese joint venture, Teva-Kowa Pharma, acquired a 66% stake in generics firm Taisho Pharmaceutical Industries.

In Teva’s 2010-2015 growth strategy announced in early January, the company says it will continue to acquire companies that will boost its market share in attractive geographies as well as enhance its branded business with niche specialty products.

“Only those who are agile and strong will survive in this business,” according to Teva president and CEO Shlomo Yanai during the company’s investor meeting last month in Jerusalem. “About 15% of our business will come from acquisitions. We are taking the necessary steps and building our infrastructure by getting assets and know-how either internally, through acquisition or partnerships.” Teva estimates its 2009 global sales at $13.9bn, of which 70% are from generic products. Yanai is targeting $31bn in sales by 2015, of which 70% will still come from generics.

“There is still room to grow in generics,” says Yanai. “Almost $150bn of branded drugs are going to be off patent in the next five years. This does not include the expiration of biologics, which is an additional $50bn potential.” Teva projects that the global generics market will reach between $135bn and $150bn by 2015. BCC estimates the global market to reach $129.3bn by 2014, representing a 9% annual growth rate.

BOOMING MARKETS

While generics firms are eagerly awaiting the ticking patent expiration of several branded blockbuster drugs, manufacturers are also monitoring the increasing emergence of government health care reforms worldwide.

In almost any given country in the world, you may see different kinds of initiatives or reforms on their own health care systems or even regulating their own pharmaceutical industry. This will increase the pace of generic drug penetration, especially in countries that are asking for better health care.

International markets are especially ripe for generics. In the $59bn global generics market in developed countries, Japan only accounts for 6%, while the US holds 42%, and five major European national markets account for 23%.

China, India, Eastern European countries and Brazil are rising centers of generics activity in emerging markets, Evers adds.

Big pharmaceutical companies are even buying generics firms to get into these emerging markets.As an example France-based Sanofi Aventis’s acquisitions last year of Brazil’s Medley and Mexico’s Kendrick, and in 2008 of Czech Republic-based Zentiva. UK-based GlaxoSmithKline (GSK) acquired Aspen of South Africa in July 2008, while at the same time, Japan’s Daiichi Sankyo acquired India’s Ranbaxy.

US-based Pfizer is now also reportedly in a bidding war against Teva for the acquisition of Germany’s Ratiopharm. In 2009, Ratiopharm holds 3% of the global generics market.

Pfizer started increasing its activities in generics last year with an expanded relationship with Indian firm Aurobindo in March and a commercialization deal with Indian injectable generics specialist Claris Lifesciences. Last month, Pfizer announced a deal with US-based Strides Arcolab to commercialize off-patent sterile injectable and oral products.

At this point, it looks like Pfizer is really geared up towards expanding more into the generics market. Still, not everything is expected to be rosy for the generics market, especially after 2013, when patent expiries will be significantly lower.

The slowing growth in branded blockbusters being developed by research and development-based manufacturers will ultimately lead to fewer opportunities for generics companies.They are now looking ahead and trying to compete in a less crowded and less competitive market such as in biosimilars.

Biosimilars are generic versions of biotechnology-based drugs.

REGULATORS CLOSE IN ON PAY-FOR-DELAY DEALS

Generic and branded pharmaceutical companies are not always at each other’s throats. Both the US Federal Trade Commission (FTC) and the European Commission announced their closer scrutiny of the so-called “pay-for-delay” deals, where branded drug companies pay generics firms to delay the market launch of their generic drugs for a certain period of time.

Last month, the Commission asked companies including AstraZeneca, GlaxoSmithKline and Niche Generics, all of the UK, Gemany’s Boehringer Ingelheim, Novartis and Roche, both Swiss, and France’s Sanofi-Aventis to provide information pertaining to generics settlement agreements in Europe between July 2008 and December 2009.

From now on, the Commission also plans to gather this data on an annual basis in the same way as the FTC, which produces annual reports detailing the type and frequency of settlement agreements undertaken by US pharmaceutical companies.

The FTC released a report in January that claimed that the number of pay-for-delay deals in the US increased from zero in 2004 to a record 19 in 2009. The deals are said to cost consumers $35bn (€25bn) over 10 years. The Commission, meanwhile, estimates that these kinds of deals could have cost European consumers €3bn ($4bn) between 2000 and 2007.

FDA Approves New Vaccine Cervarix for Prevention of Cervical Cancer

admin — Wed, 30 Dec 2009 23:05:35 +0000

The FDA today approved Cervarix, a new vaccine to prevent cervical cancer and precancerous lesions caused by human papillomavirus (HPV) types 16 and 18. The vaccine is approved for use in girls and women ages 10 years through 25 years.

Genital HPV infections are the most common sexually-transmitted diseases in the United States, and HPV types 16 and 18 are the cause of about 70 percent of cervical cancers worldwide. There will be an estimated 11,270 new cases and 4,070 deaths from cervical cancer in the United States during 2009, according to the National Cancer Institute at the National Institutes of Health.

“The licensure of Cervarix adds another option in the prevention of cervical cancer” said Karen Midthun, M.D., acting director of the FDA’s Center for Biologics Evaluation and Research. “It has the potential to save lives from cervical cancer as well as reduce the need for biopsies and invasive procedures associated with the necessary follow-up from abnormal Pap tests.”

The primary clinical study for Cervarix included more than 18,000 women ages 15 years through 25 years in the United States and 11 other countries. Of these women, about 9,000 received Cervarix and 9,000 received Havrix, a licensed hepatitis A virus vaccine, as a control.

The results showed that among women who had not already been infected by HPV types 16 and/or 18 before the start of the study, Cervarix was about 93 percent effective in preventing precancerous cervical lesions caused by these HPV types. Among all Cervarix vaccinees, which included those who tested negative for HPV 16 and/or 18, and those who tested positive at the start of the study, Cervarix was approximately 53 percent effective in preventing precancerous cervical lesions.

Studies also were performed to measure the immune response to Cervarix in girls ages 10 years through 14 years. Their immune response was similar to that of women ages 15 years through 25 years, indicating that the vaccine should have similar effectiveness in the 10 through 14 year age group.

The current data show that Cervarix provides protection for about 6.4 years, but additional information on the length of protection is forthcoming.

No vaccine is 100 percent effective, and Cervarix does not protect against HPV infections that an individual may already have at the time of vaccination, nor does Cervarix necessarily protect against those HPV types not in the vaccine. Therefore, regular Pap tests continue to be recommended for all women who receive Cervarix. Pap screening remains critically important to detect precancerous changes, which would allow treatment before cancer develops.

Cervarix contains the adjuvant ASO4. ASO4 is a combination of aluminum hydroxide and monophosphoryl lipid A (MPL) and is the first vaccine licensed by the FDA that includes MPL as an adjuvant. An adjuvant is a substance incorporated into a vaccine that enhances or directs the immune response of the vaccinated individual.

The safety of the vaccine was evaluated in about 24,000 girls and women, with about 13,000 of these receiving Cervarix. The most commonly reported adverse reactions in the Cervarix group included pain, redness, and swelling at the injection site, fatigue, headache, muscle and joint aches, and gastrointestinal distress.

Although Cervarix is not indicated for pregnant women, the FDA is requiring the manufacturer, GlaxoSmithKline Biologicals to conduct a postmarketing study to assess the safety of Cervarix in pregnant women following vaccination prior to identification of pregnancy. Women who are pregnant, or think that they may be pregnant, or plan to become pregnant during the vaccination course, should not use Cervarix.

Cervarix is administered in three separate shots, with the initial dose being followed by two additional shots at one and six months.

Cervarix is manufactured by GlaxoSmithKline Biologicals, based in the United Kingdom.

Teresa Heinz heir to the Heinz ketchup fortune fighting cancer

admin — Fri, 25 Dec 2009 23:58:47 +0000

Teresa Heinz, a part-time Wood River Valley resident for more than 30 years, has announced that she is being treated for breast cancer, but has a 95 percent chance of recovery.

Heinz, 71, and her husband, Massachusetts Sen. John Kerry, the 2004 Democratic presidential nominee, own a house just north of Ketchum along the Big Wood River.

On Wednesday, Heinz—the widow of Sen. John Heinz, heir to the Heinz ketchup fortune—told that she found out in late September that she had cancer in her left breast after having her annual mammogram.

In early October, she underwent lumpectomies on both breasts at a Washington hospital after doctors also discovered what they thought was a benign growth on her right breast. That diagnosis was initially confirmed in post-operative pathology, but two other doctors later found it to be malignant. In November, Heinz had another pair of lumpectomies performed at Massachusetts General Hospital.

Doctors also inserted titanium clips in the tissue of both breasts during the operations, and next month she will receive five days of targeted radiation. Heinz contended that younger women should continue undergoing mammograms despite a federal panel’s recent recommendation to reduce their frequency.

“Chemotherapy is serious,” she said. “It also costs a lot of money. It’s very painful. And it’s very destructive of people’s—most people’s—lives, for a while anyway. So why put people through that instead of just having a test that’s done, and it’s done? So that’s why I was so upset about that decision of this panel.”

Heinz has been a significant contributor to nonprofit organizations within the valley, including a $325,000 donation in 1992 from the Heinz Family Foundation to purchase and preserve Galena Lodge, a popular Nordic skiing destination north of Ketchum. Heinz was also the keynote speaker at the 2006 Sun Valley Sustainability Conference.

Alzheimer’s Can Lower Risk of Cancer

admin — Fri, 25 Dec 2009 23:36:49 +0000

The results of a recent study suggest that people suffering from Alzheimer’s disease are less likely to develop cancer and people with cancer are less likely to contract Alzheimer’s disease.

A group of 3,020 people aged 65 and older were selected. Of this group, 164 people already had Alzheimer’s disease and 522 people already had a cancer diagnosis. Researchers tracked the group for an average of five years to see whether they developed dementia and an average of eight years to see whether they developed cancer.

The 164 people with Alzheimer’s were found to be 69 percent less likely to undergo hospitalization for cancer during the study period.

The 522 people who had cancer were 43 percent less likely to develop Alzheimer’s disease over the course of the study period.

While the reasons for these results are not clear the connection between the two may prove to be significant. Catherine Roe from Washington University School of Medicine in St Louis, had this to say about the results of the study: “Discovering the links between these two conditions may help us better understand both diseases and open up avenues for possible treatments.”

More in depth studies into the correlation are planned.

Revlimid Meets Primary Endpoint In A Phase III Study

admin — Sat, 19 Dec 2009 08:03:26 +0000

The initial data from a Phase III study using the Revlimid in multiple myeloma patients who had undergone stem cell transplant reported that the trial had met its primary endpoint of a statistically significant improvement in time to disease progression.

The investigational study evaluated Revlimid compared to placebo in multiple myeloma patients following autologous stem cell transplant, and the independent Data and Safety Monitoring Board reported that the trial had met its primary endpoint of a statistically significant improvement in time to disease progression.

The Phase III, randomized, double-blind, multi-center clinical study was led by the Cancer and Leukemia Group B, or CALGB, and the independent Data and Safety Monitoring Board reported that the trial had met its primary endpoint of a statistically significant improvement in time to disease progression. The study was sponsored by the National Cancer Institute under a Clinical Trials Agreement with Celgene.

Revlimid, in combination with dexamethasone, is already indicated for the treatment of multiple myeloma patients who have received at least one prior therapy.

The Revlimid pivotal MM-015 trial exceeded pre-specified interim efficacy endpoint in newly diagnosed Multiple Myeloma. Further results from the study will be presented in a peer-reviewed setting in 2010.

Bosentan Improves Cardiovascular Parameters in Patients With Pulmonary Hypertension Associated With COPD

admin — Wed, 18 Nov 2009 12:57:32 +0000

In patients with moderate to severe chronic obstructive pulmonary disease (COPD) and pulmonary hypertension (PH), bosentan plus best conventional care produced greater improvement in cardiovascular parameters than best conventional care alone.

Pietro B. Bracciale, MD, Department of Respiratory Disease, San Pietro Vernotico Hospital, Brindisi, Italy, reported the findings on November 3 here at CHEST 2009, the annual meeting of the American College of Chest Physicians.

For the study, 40 patients with moderate to severe COPD and PH were treated with best conventional care for 1 month, at which time they were reassessed. Patients with persistent PH (not reversible during oxygen administration) were randomised to receive placebo plus conventional treatment or to bosentan 125 mg BID plus conventional care for 18 months.

Pulmonary function tests, Doppler echocardiography, right heart catheterisation, 6-minute-walk test distance (6MWD), blood gas analysis, and quality of life were assessed at the beginning and end of the study. Of the patients, 32 completed the study (16 in each group).

After 18 months of treatment, there were significant changes from baseline in the bosentan combination group but not in the conventional treatment group for mean pulmonary artery pressure (P = .002 vs NS), mean pulmonary vascular resistance (P = .0115 vs NS), distance on the 6MWD (P = .0027 vs NS), World Health Organization Functional Class (P = .05 vs NS), and the body mass index, airway obstruction, dyspnoea, and exercise capacity index (P = .002 vs NS).

According to Dr. Bracciale, bosentan should be a useful early treatment for patients affected by PH and moderate to severe COPD before pathologic vessel changes have occurred. The beneficial effect of bosentan may be partially linked to its vasodilating action and its effect on vascular remodelling.

Bortezomib in multiple myeloma

admin — Tue, 27 Oct 2009 21:18:54 +0000

“This novel proteasome inhibitor appears to improve response rates and
survival in patients with progressive multiple myeloma.”

Bortezomib (Velcade) is an inhibitor of the proteasome, a ubiquitous multi-enzyme complex that degrades proteins that regulate cell-cycle progression and induces proteolysis of IκB, the inhibitor of nuclear factor-κB. Increased activation of nuclear factor-κB promotes cell survival, stimulates growth, and inhibits apoptosis, as well as induces drug resistance in myeloma cells. Recent studies have demonstrated the efﬁcacy and safety of bortezomib in patients with relapsed, refractory myeloma.

Efﬁcacy studies

In the phase II SUMMIT study (n = 202), treatment with bortezomib 1.3 mg/m2 twice weekly for 2 weeks, followed by 1 week without treatment, for up to 8 cycles (24 weeks) resulted in an overall response rate of 35% (including a complete response in 4% in whom myeloma protein was undetectable and a complete response in 6% in whom myeloma protein was detectable only by immunoﬁxation).1 In the phase II CREST study, treatment with bortezomib 1.0 mg/m2 (n = 28) or 1.3 mg/m2 (n = 26) on days 1, 4, 8, and 11 every 3 weeks for up to 8 cycles (6 months) resulted in an overall response rate of 33% (4% complete response) for the 1.0-mg/m2 dose and 50% (4% complete response) for the 1.3-mg/m2 dose.2 A group of 14 patients from the CREST study and 43 from the SUMMIT study who had a partial or minimal response to bortezomib or stable disease continued receiving the proteasome inhibitor in an extension study. Most of these patients had already received 8 cycles of bortezomib therapy in the original studies. Preliminary data from the extension study indicated that bortezomib can be administered for up to 13 cycles with a safety profile similar to that observed in the first 8 cycles of treatment.

Safety demonstrated in renally impaired patients

Renal impairment is a common complication of myeloma and its treatment, and preclinical studies indicate that bortezomib and its metabolites are eliminated by both the renal and hepatic route. An analysis of outcomes in 10 patients with severe renal impairment (creatinine clearance, 10–30 mL/min) in these two studies suggests that bortezomib may be safely given to such patients, with responses and toxicities being comparable to those in patients without severe renal impairment.3 Of the 10 patients, 2 had a partial response and 1 had a minimal response; treatment was well tolerated, with 7 patients receiving at least 30 of the 32 possible study doses.

Pharmacokinetic analysis of eight patients with an initial creatinine clearance rate of 31–169 mL/min in the SUMMIT study indicated that the maximum concentration and distribution half-life of bortezomib were not affected by renal status and that the area under the concentration-time curve was similar to that obtained in the overall population.

Superior to dexamethasone

The APEX Study Group recently reported ﬁndings from their international, multicenter phase III trial comparing bortezomib with dexamethasone in patients with relapsed multiple myeloma.4 Patients were randomized to receive intravenous bortezomib 1.3 mg/m2 (n = 327) on days 1, 4, 8, and 11 every 3 weeks for 8 cycles, followed by the same dose on days 1, 8, 15, and 22 every 5 weeks for 3 cycles, or oral dexamethasone 40mg (n = 330) on days 1–4, 9–12, and 17–20 every 5 weeks for 4 cycles, followed by 40 mg on days 1–4 every 4 weeks for 3 cycles. At the time of the interim analysis, 254 progressive disease events had occurred. Median time to disease progression (using European Group for Blood and Marrow Transplantation criteria) was 5.7 months in the bortezomib-treated group versus 3.6 months in the dexamethasone-treated group (P < 0.0001). Overall survival was signiﬁcantly longer in patients receiving bortezomib than in those taking dexamethasone (P = 0.038). At the time of the interim analysis, 13 patients treated with bortezomib and 24 patients given dexamethasone had died; median survival had not yet been reached in either treatment arm.

Signiﬁcantly fewer patients taking bortezomib than those who were treated with dexamethasone developed grade 3 or worse infections (6.7% vs 10.6%, P = 0.096). No other major differences in safety were observed between treatment groups, and no difference was observed between treatment groups with regard to time to skeletal events On the basis of the interim analysis, it was recommended that the dexamethasone treatment arm be terminated in the APEX Study, and patients in the dexamethasone treatment group were permitted to receive bortezomib.

The major side effects of bortezomib are gastrointestinal symptoms, transient thrombocytopenia, fatigue, and peripheral neuropathy. Other, less frequent side effects include fever, rash, headache, and dizziness.

Iressa (gefitinib) Improves Progression-free Survival over Standard Chemotherapy

admin — Sat, 24 Oct 2009 23:25:50 +0000

Iressa (gefitinib) Improves Progression-free Survival over Standard Chemotherapy in Patients with NSCLC with EGFR Mutations.

Researchers from Japan have reported that Iressa (gefitinib) alone improves outcomes of patients with non–small cell lung cancer (NSCLC) with epithelial growth factor receptor (EGFR) mutations compared with patients receiving Paraplatin (carboplatin) and Taxol (paclitaxel). The details of this study were presented at the Joint ECCO 15 – 34th ESMO Multidisciplinary Congress in Berlin, September 20-24, 2009.

Oral Iressa (gefitinib) is approved in the United States as a single-agent treatment for patients with advanced NSCLC who have failed platinum- and taxane-based treatment. Iressa is a selective inhibitor of EGFR-tyrosine kinase. Epidermal growth factor receptor is expressed, overexpressed, or dysregulated in many human solid tumors, including NSCLC. Activation of this receptor is believed to promote tumor growth by blocking apoptosis and by increasing cell proliferation, adhesion and invasive capacity, and motility. Responsive lung tumors are likely to be adenocarcinomas or bronchio-alveolar carcinomas and occur more frequently in non-smokers and women. Responses also occur more frequently in patients with specific mutations of EGFR. Recently, researchers from Asia have reported that first-line treatment with Iressa improves progression-free survival (PFS) over combination treatment with Paraplatin and Taxol in advanced NSCLC among nonsmokers and former light smokers.

The current study included 198 patients with NSCLC with sensitive EGFR mutations who had received no prior chemotherapy. They were randomly allocated to receive Iressa alone or Paraplatin and Taxol.

Overall response rate was 74.5% for patients receiving Iressa versus 29% for patients receiving Paraplatin and Taxol. Grade 4 neutropenia occurred in 1% of patients receiving Iressa and 33% of patients receiving chemotherapy. Grade 3-4 liver dysfunction occurred in 33% of patients receiving Iressa versus 1% receiving chemotherapy. Grade 3 neuropathy occurred in 0% of patients receiving Iressa and 5% of patients receiving chemotherapy. PFS was 10.4 months following Iressa treatment versus 5.5 months for chemotherapy. Overall survival was 28.0 months for patients receiving Iressa and 23.6 months for patients receiving chemotherapy (P=0.357).

This study shows that Iressa improves PFS in patients with NSCLC with EGFR mutations compared with conventional chemotherapy. These authors suggest that Iressa be considered the new standard treatment for “sensitive EGFR mutation-positive NSCLC patients.”