Shionogi?s peramivir as Effective as Tamiflu in Tests

[Shiloh]

Source: http://online.wsj.com/article/BT-CO-20090524-703493.html

* MAY 24, 2009, 7:07 P.M. ET

Shionogi To Sell Newly Developed Flu Drug In Japan -Kyodo

OSAKA (Dow Jones)--Shionogi & Co. (4507.TO) is expected to market a new influenza drug possibly from next year in Japan, giving more options for flu treatment, Kyodo News reported Sunday, citing industry sources.

The plan comes at a time when the new strain of H1N1 influenza is threatening to grow into a possible global pandemic.

Another Japanese drugmaker, Daiichi Sankyo Co. (4568.TO), also aims to sell a new drug from around next year. Flu patients can have choices besides Tamiflu and Relenza now available from European firms, they said.

Shionogi's new prescription drug, called Peramivir, will be injected, while Tamiful is an oral drug and Relenza is to be inhaled.

When a person is not seriously ill, one injection would be sufficient and the drug would be effective even if it is given to a patient after the onset of flu, according to the sources.

In trials, the Shionogi drug demonstrated therapeutic effects against the deadly H5N1 avian flu as well, they said.

In 2007, Shionogi was granted by U.S. firm BioCryst Pharmaceuticals Inc. (BCRX) the exclusive rights to develop and sell Peramivir in Japan.

 

[Sally Furniss]

Re: Shionogi To Sell Newly Developed Flu Drug In Japan -Kyodo

Re: Shionogi To Sell Newly Developed Flu Drug In Japan -Kyodo

Shionogi?s Flu Drug as Effective as Tamiflu in Tests (Update4)
2009-07-17 20:06:50.804 GMT


By Kanoko Matsuyama
July 17 (Bloomberg) -- Shionogi & Co., a Japanese
drugmaker, said its experimental influenza drug was as effective
as Roche Holding AG?s Tamiflu in treating flu patients in the
last stage of patient studies required for regulatory approval.
Shionogi?s peramivir, in phase-three testing, took a median
of 78 hours to relieve symptoms of seasonal influenza in
patients who were given 300-milligram doses and 81 hours for 600
milligrams, the company said in a statement today. That compares
with 81.8 hours for Tamiflu, of which patients took 75
milligrams twice a day for five days.
The Osaka-based company plans to file its data to Japan?s
health ministry for marketing approval of the drug this year,
Shionogi spokesman Masahiro Fujita said by telephone.
In March 2007, Shionogi agreed to pay as much as $35
million to Birmingham, Alabama-based BioCryst Pharmaceuticals
Inc. for rights to develop and sell intravenous-drip peramivir
in Japan and Taiwan.
BioCryst rose $1.73, or 41 percent, to $5.95 at 4 p.m. New
York time in Nasdaq Stock Market composite trading. The stock
has more than doubled in the past 12 months.
Shionogi rose 2.9 percent to close at 1,831 yen on the
Tokyo Stock Exchange, the biggest gain since May 25. The
benchmark Nikkei 225 Stock Average advanced 0.6 percent.

Bloomberg.com

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[SuperNova1987A]

Re: Shionogi?s peramivir as Effective as Tamiflu in Tests

July 17, 2009
Shionogi & Co., Ltd.

Shionogi announces positive results from Phase3 studies of peramivir, a novel anti-viral drug for influenza

Shionogi & Co., Ltd. (Head office: Osaka; President: Isao Teshirogi) today announced that it has achieved the primary objectives of two Phase3 clinical studies of peramivir (a neuraminidase inhibitor, S-021812) for seasonal influenza virus infection that were conducted during the 2008-2009 influenza season.

In patients with uncomplicated seasonal influenza, Shionogi conducted a three-armed, multi-center, randomized, double-blind, multi-national Asian study that compared the efficacy and safety of a single dose treatment of i.v. peramivir (either 300 mg or 600 mg) and oral treatment with oseltamivir phosphate (Tamiflu?) twice a day for 5 days. A total of 1,099 uncomplicated patients infected with seasonal influenza virus were enrolled at 146 centers (Japan:100; Korea＊:25; Taiwan:21). Both the 300 mg and 600 mg single
dose peramivir groups demonstrated non-inferiority for the primary endpoint, time to alleviation of symptoms (TTAS), compared to that the oseltamivir group. The medians for the TTAS for the peramivir 300 mg, peramivir 600 mg and oseltamivir groups were 78.0 hrs, 81.0 hrs and 81.8 hrs, respectively. Occurrence rate of adverse drug reaction was significantly reduced in the 300 mg of peramivir group compared to that of Tamiflu group.
＊：Shionogi and Green Cross Corporation, the license holder of peramivir in Korean, co-conducted the portion of the studies in Korea

Additionally, Shionogi conducted a double-blind, multi-center Phase3 study of i.v. peramivir with dosing over multiple days. The study enrolled 42 influenza patients at high-risk of serious complications due to one or more qualifying conditions: diagnosis with poorly controlled diabetes mellitus, a chronic respiratory disease requiring pharmacotherapy, or current treatment with any immunosuppressive drug. Peramivir was administered at 300 mg i.v. or 600 mg i.v. per day, and the duration was adjusted (up to 5 days) on a case-by-case basis, depending on the patient?s temperature and clinical condition. In this study, the median time to alleviation of symptoms in all 37 evaluable patients treated with either 300 mg or 600 mg peramivir daily was 68.6 hrs. The median time of each group (300mg and 600mg) were 114.4hrs and 42.3hrs, respectively. The results indicated that the symptoms of influenza of patients with high risk, which is believed to be prolonged were also improved in shorter period.

Peramivir 300 mg or 600 mg i.v. single and multiple doses were generally safe and well tolerated in these trials. Further analyses of the study data, including secondary efficacy endpoints and detailed safety is underway. Additional data will be submitted for presentation at an upcoming medical meeting.

A new anti-influenza virus drug is desirable for suppressing the prevalence of swine-origin influenza (A/H1N1) and human-to-human infection of highly pathogenic avian influenza (A/H5N1). Shionogi recognizes that to limit the prevalence of pandemic influenza is a social mission for Shionogi. To accomplish the mission, Shionogi has been making its best effort to file the New Drug Application and to get a manufacturing approval as soon as possible.

About peramivir
Peramivir, licensed from US-based BioCryst Pharmaceuticals, Inc. (Head Office: Birmingham, Alabama; CEO: Jon P. Stonehouse) is neuraminidase inhibitor for intravenous infusion being developed by Shionogi in Japan. Highly potent activity of peramivir against influenza A and B viruses has been hown. It has also shown that peramivir has active against highly pathogenic H5N1 (avian flu) viruses. Because of strong binding to neuraminidase and the fact it is not easily dissociated, peramivir is expected to work sufficiently against seasonal influenza virus infection.

Forward-Looking Statements
This announcement contains forward-looking statements. These statements are based on expectations in light of the information currently available, assumptions that are subject to risks and uncertainties which could cause actual results to differ materially from these statements. Risks and uncertainties include general domestic and international economic conditions such as general industry and market conditions, and changes of interest rate and currency exchange rate. These risks and uncertainties particularly apply with respect to product-related forward-looking statements. Product risks and uncertainties include, but are not limited to, completion and discontinuation of clinical trials; obtaining regulatory approvals; claims and concerns about product safety and efficacy; technological advances; adverse outcome of important litigation; domestic and foreign healthcare reforms and changes of laws and regulations. Also for existing products, there are manufacturing and marketing risks, which include, but are not limited to, inability to build production capacity to meet demand, unavailability of raw materials and entry of competitive products. The company disclaims any intention or obligation to update or revise any forward-looking statements whether as a result of new information, future events or otherwise.

For further information, contact:Corporate Communications Department
Shionogi & Co., Ltd.
Telephone: +81-6-6209-7885
Fax: +81-6-6229-9596

Source: http://www.shionogi.co.jp/ir_en/news/detail/e_090717.pdf

 

[Sally Furniss]

Re: Shionogi?s peramivir as Effective as Tamiflu in Tests

from another thread

Summary: Clinical trials that are finished have given positive results. FDA has proceeded with a pre-Emergency Use Authorization (EUA) review of peramivir, and if an order is placed for the Strategic National Stockpile, BioCryst has the manufacturing supplies it needs to finish the product and make large quantities available.

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[snips]
Peramivir is a potent, specific influenza viral neuraminidase inhibitor (NAI) discovered at BioCryst that will be used for uncomplicated influenza and influenza requiring hospitalization. Parenteral peramivir is now completing phase-3 clinical trials conducted by BioCryst's partner Shionogi & Co. Ltd. in Japan (enrollment is completed but data is not yet available) and is ready to enter phase-3 trials in the United States for influenza indications.

These expanded studies of 204 unique clinical isolates have demonstrated that this new virus is very sensitive to peramivir, with a median IC50 of 0.09nM in the NAI chemiluminesence assay; the IC50 for peramivir is significantly lower than that for either zanamivir or oseltamivir (p < 0.001). Peramivir improves survival in preclinical influenza models, including mouse and ferret models of highly pathogenic avian influenza H5N1. One day of peramivir treatment is active, and multiple days of treatment rescues most or all mice with H5N1. Similar results have been observed in ongoing murine experiments with seasonal influenza A (H1N1)/H274Y.

Peramivir achieves very high plasma levels after parenteral administration, is not metabolized, and is cleared by renal filtration. It has a long half-life, especially compared with other NAIs. Because the drug is not metabolized, is widely distributed, and is excreted unchanged in urine, dosing regimens can be adapted easily for patients with renal impairment and for pediatric populations.

Clinical data has been generated for peramivir in several phase-2 and phase-3 studies, and the drug has been administered safely to more than 1,300 subjects in clinical studies.

The primary endpoint (in the Japan studies) was time to alleviation of symptoms (TTAS) and was unequivocally positive. The time to alleviation of symptoms was 81.8 hours for placebo, and was shortened by about 22 hours with peramivir (p=0.0046). Time to resolution of fever was also significantly improved in the peramivir groups compared to placebo. Evaluations in the change in viral load showed that viral clearance was significantly accelerated in the 600mg peramivir group compared to placebo.

The safety experience for peramivir was very satisfactory in this study. Reported AEs were mild, and no serious AEs were reported in the 198 subjects administered peramivir in the study. The reported AEs were of similar frequency and severity grade in the placebo and treatment groups.

BioCryst's phase-2 study of peramivir in patients with influenza requiring hospitalization
An important issue for influenza clinical research is lack of awareness of influenza in the hospital setting. This problem seems partly due to lack of reliable diagnostic tests in emergency rooms - it is estimated that only 5% of patients hospitalized with influenza actually receive that diagnosis.

The patient population enrolled consisted mostly of individuals admitted with chronic illness that worsened with influenza, and not patients with influenza-pneumonia. The study patients had good clinical outcomes, and BioCryst was pleased with the rapidity of clearance of the virus. Viral cultures were obtained from nasopharyngeal swabs at regular intervals. Overall, viral load was reduced rapidly with treatment.

Looking at AEs, peramivir IV once daily for 5 days was generally safe and well-tolerated in adults hospitalized with acute influenza.

Dr. Sheridan described one case of compassionate use of peramivir under emergency IND regulations in Seattle.
Data for the presentation was kindly provided by the investigator, Dr. Anna Wald, Seattle WA. This patient had had a bone marrow transplant and presented to the ED with respiratory and GI symptoms 2 days after the transplant. The patient was diagnosed with influenza A (subsequently confirmed to be due to the pandemic strain) developed bilateral viral pneumonia, and rapidly deteriorated despite treatment with oseltamivir, adamantane and ribavirin. Virus was detected by PCR in blood and stool as well as bronchoalveolar lavage specimens. Intubation, 100% inspired oxygen and positive end-expiratory pressure were required. Following a 10-day course of peramivir combined with oseltamivir, the patient's condition improved, allowing discharge from the intensive care unit and cessation of antivirals. Dr. Sheridan said that although the case provides anecdotal evidence, it illustrates the potential for successful use of peramivir for severe illness.

Peramivir can be made available as a countermeasure for the current H1N1 pandemic. FDA has proceeded with a pre-Emergency Use Authorization (EUA) review of peramivir, and if an order is placed for the Strategic National Stockpile, BioCryst has the manufacturing supplies it needs to finish the product and make large quantities available. The manufacturing process is well developed.

From H1N1 COUNTERMEASURES STRATEGY AND DECISION-MAKING FORUM; 100 page .pdf http://www.hhs.gov/aspr/conferences/nbsb/nbsb-h1n1forum-sum-090617.pdf