Replies to post #77134 on Biotech Values

[pharmaclown35]

20-Apr-09 13:13 Viropharmas's Cinryze and CSL Behring's Berinert P for acute HAE bolstered by long-term safety data; competitors leverage subcutaneous delivery – analysis
Story Viropharma's (NASDAQ:VPHM) Cinryze and CSL Behring's Berenert P have long-term safety data to make their case for approval in acute attacks of hereditary angioedema, physicians said. However, acute attacks can have a rapid onset, making subcutaneous delivery with the potential for self-administration attractive, they said.

Hereditary angioedema (HAE) is a rare disorder caused by deficient or improper function of the plasma protein C1 inhibitor (C1-INH) causing swelling in various parts of the body. The disease can be fatal when swelling occurs in the larynx. In the US, five agents are currently in testing or jockeying for approval.

Cinryze and Berenert P are both C1 esterase inhibitors. C1 esterase inhibitors have been used in Europe for many years for both acute attacks and prophylaxis, according to Dr Albert Sheffer, clinical professor of medicine at Harvard Medical School. In the US, for acute attacks, the only current treatment is fresh frozen plasma, he said.

Cinryze is currently approved in the US for prophylaxis in HAE and has a PDUFA date set for 3 June 2009 for its BLA submission for acute treatment. Berenert P is approved in Europe, and has filed a BLA with the FDA on 6 March 2008. Both treatments must be delivered intravenously in a physician's office or medical facility. CSL Behring is currently running a comparative trial of IV vs. subcutaneous delivery of Berenert P, according to clinicaltrials.gov.

Cinryze and Berenet P are purified proteins taken from donors and are then administered as replacement for the C1 inhibitor that is lacking in patients with HAE, said Dr Michael Frank, professor of pediatrics at Duke University Medical Center.

Having been used in Europe extensively, Dr Andreas Lehmann at the Clinic for Anesthesiology and Operative Intensive Medicine in Germany said C1 inhibitors are a good treatment for acute attacks as well as prophylaxis. "Short-term prophylactics are needed for surgery, and long-term prophylactics are needed for severe HAE," he said. C1 inhibitors have a long history of use, though all the therapies in testing will be efficacious, he said.

Dyax's DX-88, a kallikrein inhibitor, received a REMS notice from the FDA on 26 March 2009. The advantage of DX-88 is that, in addition to clear efficacy, it can be delivered subcutaneously, with the potential for self-administration, physicians said.

"The ultimate goal is to put it in the hands of patients, but the fact that we are worried about serious side effects [such as anaphylaxis], this is hard to reach," said Dr Marc Riedl at the David Geffen School of Medicine at UCLA. However, the subcutaneous delivery method, even if given in a physician's office, is advantageous, he added.

"The difficulty with HAE is that intermittent swellings can happen anytime," said Dr Hilary Longhurst a consultant immunologist at Barts and the London NHS Trust. "There is always a risk of asphyxiation," she said. Longhurst added that due to the rapid presentation of acute symptoms, a subcutaneous delivery would offer a real advantage, especially if it could be self-administered or given by family practitioners who are less inclined to use IV delivery for acute care.

A fourth compound, Jerini's icatibant, will begin a confirmatory Phase III trial in 3Q09 after receiving a "Not Approvable" letter from the FDA in April 2008, according to a company press release. Icatibant is currently approved in Europe for acute treatment of HAE and marketed as Firazyr by Germany-based Jerini. Firazyr is a first-in-class compound that works on the B2 receptor as an antagonist to bradykinin, working further downstream than C1 inhibitors. Firazyr is delivered subcutaneously, but not self-administered.

Dutch biotechnology company Pharming (AMS:PHARM) is also testing rhucin, a recombinant protein made in rabbits. The company will submit application for approval to the European Medicines Agency in September 2009 and will request a pre-BLA meeting at the FDA in the second half of 2009.
by Janan Cargile

Source Pharmawire

[DewDiligence]

VPHM – FDA Requires New Study for Cinryze in Acute HAE

[Cinryze was approved by the FDA for prophylactic use in Oct 2008 (#msg-32795311).]

http://phx.corporate-ir.net/phoenix.zhtml?c=92320&p=irol-newsArticle&ID=1296156

›ViroPharma Receives Complete Response Letter for Cinryze Supplemental Biologics License Application for Acute Treatment of Hereditary Angioedema

- Company Also Granted Expansion of Prophylaxis Therapy Label to Include Patient Labeling for Self-Administration -

EXTON, Pa., June 4 /PRNewswire-FirstCall/ -- ViroPharma Incorporated (Nasdaq: VPHM) today announced that it has received a Complete Response letter from the U.S. Food and Drug Administration (FDA) related to its supplemental Biologics License Application (sBLA) for Cinryze (C1 esterase inhibitor [human]) as a treatment for acute attacks of hereditary angioedema (HAE). The FDA has requested an additional clinical study, due to their opinion that the placebo controlled study submitted in support of the sBLA lacked robustness. In the Complete Response letter, the FDA cited no safety concerns related to acute treatment with Cinryze in the clinical studies.

In addition, ViroPharma announced that FDA has approved the patient labeling for Cinryze to include self-administration for routine prophylaxis, once patients are properly trained by their healthcare provider.

"Though Cinryze is already successfully preventing attacks of HAE in many patients, there remains an unmet medical need for patients suffering from acute laryngeal attacks," said Vincent Milano, ViroPharma's president and chief executive officer. "Despite having a statistically significant result using the most conservative intent-to-treat (ITT) analysis, the FDA feels that the data are not robust enough to support approval at this time. We intend to respond to the FDA about our plans, and we will provide an update on the second quarter financial call."

In October 2008, Cinryze was approved as the first and only targeted therapy for routine prophylaxis against angioedema attacks. In clinical studies and in commercial use, Cinryze has been generally well-tolerated. In the controlled clinical trials of Cinryze, there were no deaths or serious adverse reactions related to Cinryze administration, or discontinuations due to treatment-emergent adverse events.

"Patients in the United States with HAE have been waiting for a safe and effective emergency treatment for a long time," said Anthony Castaldo, president of the U.S. and International Hereditary Angioedema Association. "Cinryze as a prophylactic treatment has changed the lives of many people living with this debilitating disease; we look forward to a day when this important therapy will be approved in the acute setting."

Patient Labeling for Self Administration

Self-administration of Cinryze provides patients with the ability to administer Cinryze themselves, when properly trained, in the comfort of their own home. This is an important option for some patients because they may no longer need to travel to their doctor's office - sometimes hours away - every three to four days for in-office infusions. Cinryze is administered intravenously though a small needle.

"We are pleased that the FDA has recognized the importance of self-administration for patients," continued Milano. "Empowering patients to administer Cinryze themselves allows them greater flexibility in managing their disease."‹