FDA Schedules Meeting on Biosimilars

The U.S. Food and Drug Administration is scheduling a public hearing in November to discuss the development of copycat versions of biotech drugs, according to a draft notice of the meeting being circulated by the regulatory agency.
UPThe proposed public hearing is another signal that FDA is moving deliberately towards creating a regulatory framework to foster new, lower-priced competition to the biologic drugs that are the growth engines of biotech companies like Amgen(AMGN) , Biogen Idec(BIIB) , Genzyme(GENZ) and others.
The FDA's two-day meeting on so-called biosimilar drugs will be held Nov. 2-3, according to a draft Federal Register notice titled "Approval Pathway for Biosimilar and Interchangeable Biological Products."
FDA has yet to formally announce the meeting, but the draft agenda has been circulating around Washington, D.C., according to health policy analyst Alec Vashon, who disclosed the FDA's plans Friday on Twitter.
The healthcare reform bill passed earlier this year by Congress gave FDA permission to approve biosimilars, which are copies of large protein, or biologic, drugs made in cultures of living, genetically altered cells. Biologic drugs are notoriously hard to manufacture, so until now, they've been exempt from federal law that allows for the manufacture of low-cost copies of small molecule, or chemical, drugs once the patents protecting their intellectual property expires.
Generic copies of chemical drugs are considered to be identical to their brand name counterparts and existing law allows doctors and pharmacies to substitute one for the other freely.
Biologic drugs, however, are complex proteins so copycat versions may be "similar" but not completely identical or have the same efficacy and safety profile. While FDA now has the authority to approve biosimilars, the agency has struggled so far to come up with clinical testing standards to ensure that patients treated with biologic copies receive the same benefits while not being put at any greater risk.
"The Food and Drug Administration (FDA) is announcing a 2-day public hearing to obtain input on specific issues and challenges associated with the implementation of the Biologics Price Competition and Innovation Act of 2009 (BPCI Act)," states the agency's draft Federal Register notice, referring to the law which authorizes the approval of biosimilars.
"We believe the primary focus might be to better define what terms in the bio-similar legislation actually mean and to clarify exactly what the approval criteria will be for generics companies to secure true 'interchangeable' status," said ISI Group biotech analyst Mark Schoenebaum, in a note to clients Sunday.

**Published in "The Street"

PRO2000 vaginal gel for prevention of HIV-1 infection (Microbicides Development Programme 301)

--Background
Innovative prevention strategies for HIV-1 transmission are urgently needed. PRO2000 vaginal gel was efficacious against HIV-1 transmission in studies in macaques; we aimed to assess efficacy and safety of 2% and 0·5% PRO2000 gels against vaginal HIV-1 transmission in women in sub-Saharan Africa.

--Methods
Microbicides Development Programme 301 was a phase 3, randomised, double-blind, parallel-group trial, undertaken at 13 clinics in South Africa, Tanzania, Uganda, and Zambia. We randomly assigned sexually active women, aged 18 years or older (≥16 years in Tanzania and Uganda) without HIV-1 infection in a 1:1:1 ratio to 2% PRO2000, 0·5% PRO2000, or placebo gel groups for 52 weeks (up to 104 weeks in Uganda). Randomisation was done by computerised random number generator. Investigators and participants were masked to group assignment. The primary efficacy outcome was incidence of HIV-1 infection before week 52, which was censored for pregnancy and excluded participants without HIV-1 follow-up data or with HIV-1 infection at enrolment. HIV-1 status was established by rapid tests or ELISA at screening at 12 weeks, 24 weeks, 40 weeks, and 52 weeks, and confirmed in a central reference laboratory. The primary safety endpoint was an adverse event of grade 3 or worse. Use of 2% PRO2000 gel was discontinued on Feb 14, 2008, on the recommendation of the Independent Data Monitoring Committee because of low probability of benefit. This trial is registered at http://isrctn.org, number ISRCTN 64716212.

--Findings
We enrolled 9385 of 15 818 women screened. 2591 (95%) of 2734 participants enrolled to the 2% PRO2000 group, 3156 (95%) of 3326 in the 0·5% PRO2000 group, and 3112 (94%) of 3325 in the placebo group were included in the primary efficacy analysis. Mean reported gel use at last sex act was 89% (95% CI 86—91). HIV-1 incidence was much the same between groups at study end (incidence per 100 woman-years was 4·5 [95% CI 3·8—5·4] for 0·5% PRO2000 vs 4·3 [3·6—5·2] for placebo, hazard ratio 1·05 [0·82—1·34], p=0·71), and at discontinuation (4·7 [3·8—5·8] for 2% PRO2000 gel, 3·9 [3·0—4·9] for 0·5% PRO2000 gel, and 3·9 [3·1—5·0] for placebo gel). Incidence of the primary safety endpoint at study end was 4·6 per 100 woman-years (95% CI 3·9—5·4) in the 0·5% PRO2000 group and 3·9 (3·2—4·6) in the placebo group; and was 4·5 (3·7—5·5) in the 2% PRO2000 group at discontinuation.

--Interpretation
Although safe, 0·5% PRO2000 and 2% PRO2000 are not efficacious against vaginal HIV-1 transmission and are not indicated for this use.

--Funding
UK Department for International Development, UK Medical Research Council, European and Developing Countries Clinical Trials Partnership, International Partnership for Microbicides, and Endo Pharmaceuticals Solutions.

**Published in "The Lancet"

Pfizer, Boehringer Ingelheim's Spiriva shows promise for treating asthma

According to study results published in the NEJM, the addition of Pfizer's Spiriva (tiotropium) to standard therapy improves symptoms in patients whose asthma is poorly controlled and gives them more days without breathing problems. The data showed that Spiriva worked at least as well as GlaxoSmithKline's Serevent (salmeterol) and better than doubling the steroid dose. Spiriva, which is co-marketed with Boehringer Ingelheim, is already used for chronic obstructive pulmonary disease.

Reference Articles
Pfizer's Spiriva enhances asthma treatment - study - (CNBC)
Tiotropium bromide step-up therapy for adults with uncontrolled asthma - (NEJM)
Spiriva as good as Serevent in asthma study - (The Oakland Tribune)
Early trial suggests COPD drug might help some asthmatics - (Yahoo!News)

**Published in "First Word"

Agios Appoints Scott Biller, Ph.D., Industry Leader and Drug Developer, as Chief Scientific Officer

Agios Pharmaceuticals, the leading biopharmaceutical company focused on discovering and developing novel drugs in the rapidly emerging field of cancer metabolism, today announced the appointment of Scott Biller, Ph.D., as Chief Scientific Officer. Dr. Biller joins Agios from Novartis Pharmaceuticals, where he was Vice President and Head of Global Discovery Chemistry at the Novartis Institutes for BioMedical Research (NIBR).
"Scott is a world-class drug hunter who will help us achieve our vision of discovering and developing transformative medicines that target dysregulated metabolic enzymes," said David Schenkein, M.D., Chief Executive Officer, Agios. "Scott's breadth of experience and record of leadership in the industry makes him the ideal candidate to shape and lead our research initiatives, and I'm tremendously excited to welcome him to Agios."
"Agios has established the leading effort in cancer metabolism, driven by a unique culture of scientific leadership and technological innovation," said Dr. Biller. "I am convinced that we can make dramatic improvements in patient outcomes by mapping and targeting the metabolism of cancer cells. I look forward to working with the exceptional team of scientists at Agios and with the broad network of academic leaders that are collaborating with Agios on this important work."
Dr. Biller has more than 25 years of drug discovery and development experience. While at Novartis, he was responsible for the world-wide discovery chemistry functions at NIBR, including medicinal, combinatorial and computational chemistry, as well as the research metabolism and pharmacokinetics group. He joined NIBR in 2003 and played a key role in building the new research organization in Cambridge, Massachusetts, as well as reinventing the Novartis culture of innovation globally.
Prior to Novartis, Dr. Biller held the positions of Vice President, Pharmaceutical Candidate Optimization at the Bristol Myers Squibb (BMS) Pharmaceutical Research Institute, and Executive Director of Drug Discovery Chemistry for the BMS research site in Lawrenceville, NJ, where he was responsible for overseeing the research efforts for oncology, immunology, inflammation and pulmonary diseases. Among his other key leadership positions at BMS, Dr. Biller was the Executive Director of Metabolic Diseases Chemistry, with responsibility for discovery programs in hypercholesterolemia and atherosclerosis, diabetes, obesity, osteoporosis and endocrine dysfunctions of the aging population. Under his leadership, his team delivered numerous clinical candidates, including the marketed DPP4 inhibitor Onglyza (saxigliptin) for Type 2 diabetes, and two molecules currently in Phase III trials (the SGLT2 inhibitor dapagliflozin for Type 2 diabetes and the MTP inhibitor lomitapide for hyperlipidemia). He has co-authored over 90 papers and patents, and has been invited to deliver scientific lectures around the world.

**Published in "Business Wire"

Bristol-Myers says diabetes drug meets study goal

The drugmakers Bristol-Myers Squibb Co. and AstraZeneca PLC said Monday that their experimental diabetes drug dapagliflozin met its goal in a clinical trial, as the drug was more effective than an older treatment at reducing blood sugar levels.
Dapagliflozin is an oral drug intended to be taken once a day. It is designed to help type 2 diabetes patients excrete glucose and related calories in their urine. That would help prevent glucose from building up in the body.
The companies said a combination of dapagliflozin and glimepiride was better at reducing blood sugar levels than glimepiride and a placebo. Patients on dapagliflozin also lost more weight, had greater oral glucose tolerance, and lower blood sugar levels between meals after the 24-week late stage clinical trial, the companies said.
Patients took either 2.5 milligrams, 5 milligrams, or 10 milligrams of dapagliflozin per day, and the companies said those patients had median weight loss of 2.6 pounds, 3.4 pounds, and 5 pounds respectively. Patients on glimepiride alone had median weight loss of 1.6 pounds. They said rates of side effects were similar for dapagliflozin and glimepiride, but patients on dapagliflozin were more likely to have genital tract infections.
Glimepiride is marketed under names including Amaryl. It was first approved in 1995.
Results from the trial were presented at a meeting of the European Association for the Study of Diabetes in Stockholm. Bristol-Myers Squibb is based in New York, and AstraZeneca is based in the U.K.

**Published by "AP"

Roche´s Avastin fails to help early-stage colon cancer patients in study

Roche Holding AG’s Avastin tumor medicine failed to meet the main goal of a late-stage study in early colon cancer. A combination of Avastin and chemotherapy given immediately after surgery didn’t extend disease-free survival compared with chemotherapy alone, Basel, Switzerland-based Roche said today in a statement. Preliminary data from the study suggest that chemotherapy alone is more effective in treating the tumors, Roche said.
While the company hoped the benefit of giving Avastin seen in studies of late-stage colorectal cancer would “translate to the early setting, it is becoming increasingly clear that the effects of Avastin are different in the metastatic and early disease settings” in colon cancer, Hal Barron, chief medical officer at Roche, said in the statement.
The company said it is examining data from this and another study looking at a similar use of the drug to “help define the next steps” for the development of Avastin in this use.
The Food and Drug Administration yesterday said it needed more data to decide whether Avastin, in combination with certain chemotherapies, should gain approval for initial treatment of breast cancer that has spread. The regulator, which had been expected to decide by yesterday, said it would now take action by Dec. 17.

-Drug Failure
Avastin in 2008 won the accelerated approval for use of the drug in breast cancer with the chemotherapy treatment paclitaxel. The FDA may be debating whether to revoke that 2008 decision after an advisory panel in July voted 12 to 1 in favor of rescinding approval.
Study data required to convert the accelerated approval to standard approval failed to convince the panel that the drug had a “clinically meaningful” benefit over chemotherapy alone in terms of its ability to keep cancer at bay. The drug also failed to prolong survival and was associated with increased serious side effects, the panel found.
Avastin generated 1.73 billion Swiss francs ($1.71 billion) in revenue during the second quarter. The medicine was developed by the company’s South San Francisco, California-Genentech unit, fully acquired by the European drugmaker last year for $46.8 billion.

J&J on the Hunt for China M&A

Johnson & Johnson (NYSE: JNJ) is using “external innovation” in China as a low-cost, highly inventive path to discover new drugs, seeking to solve unmet needs in China as well as the rest of the world. "We have to seek the best science and technology,” said Lily Lee, PhD, vice-president and head of JNJ Pharmaceutical R&D Asia, at a recent Shanghai biopharma meeting.Continuing her discussion of J&J’s plans, she told Reuters reporters, "We are especially interested in oncology, infectious diseases and metabolic areas, so M&As in these areas will be high on our radar screen.
" J&J’s investment will grow at double-digits, Dr. Lee continued, which she doesn’t consider surprising. "Because we are growing from a small base, anything we do is in double digits." In China, J&J will focus on meeting basic medical needs – the “affordable” market is her term – instead of the high-priced drugs that solve rare conditions. With healthcare reform, that market is the fastest growing sector, and it will make China the third biggest market for drugs worldwide next year – 2011.In 2009, J&J established a regional center in Shanghai that manages the company’s diverse R&D activities in Asia – Dr. Lee’s home base. It was put on the same organizational level as centers in the US and Europe.
In May of this year, J&J established a Joint R&D Center in Oncology with Tianjin Medical University Cancer Hospital. Its goal is to establish a center that meets international standards of research. J&J had previously formed a cancer biomarker R&D project with Tianjin Cancer Hospital. The Center will explore types of cancer that are particularly important in China, including China-specific variationsLast year, the Ortho-McNeil-Janssen subsidiary of J&J announced a collaboration with Hutchison MediPharma [AIM: HCM] to work on a novel inflammation/immunology target. MediPharma was put in charge of development activities, while OMJ has an option on the work, including an option to take over the development.Another J&J subsidiary, Xian-Janssen, launched a new drug in China in 2009 after winning approval through the Green Channel, an expedited approval process. Dacogen (decitabine) is a novel treatment for myelodysplastic syndrome (MDS). The incidence of MDS in China is so low that the SFDA based its approval on trials done outside of China.

**Published in "Seeking Alpha"