Replies to post #61378 on Biotech Values

[DewDiligence]

Why is the HAE market so crowded? I can’t think of another disease with as small a patient pool that has so many companies chasing it.

[DewDiligence]

FDA Rejects Jerini’s NDA for Icatibant in HAE

[Good news for LEVP, Pharming, DYAX, and CSL Behring.]

http://biz.yahoo.com/pz/080424/140863.html

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Thursday April 24, 8:50 am ET

Jerini Expects CHMP Opinion for European Marketing Authorization Later Today

BERLIN, April 24, 2008 (PRIME NEWSWIRE) -- Jerini AG (FSE:JI4) has received a not approvable letter from the FDA for its New Drug Application (NDA) for Icatibant in the treatment of hereditary angioedema (HAE). The not approvable letter outlines areas of concern that the company is now going to review with the agency.

Jerini is expecting an opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMEA) for Icatibant in the treatment of HAE later today.
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[DewDiligence]

FDA Panel Endorses LEVP’s Cinryze

[The panel meeting nominally pertained to the BLA for the prophylactic HAE indication only; however, it’s reasonable to infer that the positive outcome reflects well on the BLA for the acute indication too. LEVP is up only modestly today because the positive panel vote was widely exepcted from the briefing docs.]

http://biz.yahoo.com/bw/080502/20080502005620.html

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Lev Announces FDA Advisory Committee Unanimously Recommends Approval of Cinryze™ for Hereditary Angioedema

Friday May 2, 1:32 pm ET

Company to Host Conference Call on Monday, May 5 at 8:30 am EST

NEW YORK & WASHINGTON--(BUSINESS WIRE)--Lev Pharmaceuticals, Inc. (OTCBB: LEVP ) today announced that the Blood Products Advisory Committee to the U.S. Food and Drug Administration (FDA) today voted unanimously that there is sufficient evidence of the safety and efficacy for the approval of Cinryze™ (C1 inhibitor) for the prophylactic treatment of hereditary angioedema (HAE), also known as C1 inhibitor deficiency.

If approved, Cinryze™ would be the first C1 inhibitor replacement therapy for patients with HAE in the U.S. HAE is characterized by extremely painful, debilitating and sometimes fatal swelling of the extremities, face, genitals, abdomen and laryngeal tract. These attacks, which affect an estimated 10,000 people in the U.S., are usually unpredictable and may be spontaneous or precipitated by emotional or physical stress.

“The advisory committee’s support of Cinryze™ represents an important advancement for HAE patients, caregivers, advocates and physicians who treat this devastating disease,” said Joshua Schein, chief executive officer of Lev. “We look forward to continuing to work with FDA to secure approval of Cinryze™ in order to serve the patients and families who suffer from HAE.”

The FDA had issued a complete response letter (or “approvable” letter) in January, in which the FDA requested information with respect to chemistry, manufacturing, and controls (CMC), as well as additional analyses of existing efficacy data from the Cinryze™ trials. No additional safety information and no additional clinical trials were requested in the FDA’s letter. Lev subsequently filed its complete response to the FDA.

The FDA will review the advisory committee’s recommendations in connection with its consideration of Lev’s BLA.

Conference Call Information

The Company will hold a conference call and audio webcast for investors on Monday, May 5, at 8:30 a.m. Eastern Standard Time (EST). The conference call will be available via live webcast on Lev's website at www.levpharma.com. To participate by telephone, the domestic dial-in number is 866-383-8108 and the international dial-in is 617-597-5343. The access code is 75322162. Investors are advised to dial into the call at least ten minutes prior to the call to register. The conference call will be available via live webcast on Lev's website at www.levpharma.com.

About Cinryze™

Cinryze™ is a plasma-derived C1 inhibitor product that has been studied for the prophylactic and acute treatment of HAE. C1 inhibitor has been used for more than 35 years in Europe to treat patients with C1 inhibitor deficiency.

In the Phase III prophylactic treatment trial, Cinryze™ decreased the normalized number of HAE attacks compared to placebo. The trial had a crossover design with 22 subjects in the efficacy data set. The difference between the number of angioedema attacks during treatment with Cinryze™ and the number during treatment with placebo was statistically significant (p<0.0001). During 12 weeks of prophylactic treatment with Cinryze™, the number of attacks per patient ranged from 0 to 17.6 with a mean of 6.3 (±5.5) and a median of 6 attacks. During 12 weeks of treatment with placebo, the number of attacks per patient ranged from 6 to 20.5 with a mean of 12.7 (± 4.6) and a median of 13.5 attacks. The clinically and statistically significant results for the primary endpoint demonstrating the efficacy of Cinryze™ were supported by statistically significant and clinically meaningful differences in all of the secondary endpoints, with Cinryze™ demonstrating reductions in the severity and duration of attacks, number of days of swelling, and need for open-label Cinryze™ rescue therapy.

In the Phase III acute treatment trial, the median time to the onset of unequivocal relief of symptoms for an acute attack was significantly different between the Cinryze™ group (2 hr) and placebo group (> 4 hr) (p=0.026). The application for the treatment of acute attacks of HAE was not presented before the Blood Products Advisory Committee and is currently under active review at FDA.

Additionally, Cinryze™ has been well tolerated with an adverse event profile no different from placebo. The most common adverse reactions observed have been upper respiratory infection and sinusitis. No drug-related serious adverse events (SAEs), no immunogenicity and no decrease in efficacy have been observed.

As part of Lev's CHANGE trials (C1 inhibitor in Hereditary Angioedema Nanofiltration Generation evaluating Efficacy), the Company is conducting two open label studies for the treatment and prevention of HAE. Qualifying HAE patients continue to have access to Cinryze™ on a compassionate use basis, free of charge. To date, more than 6,000 doses of Cinryze™ have been administered in all parts of the CHANGE trials with more than a dozen patients having individually received well over 100 doses.

About Hereditary Angioedema

HAE is a rare, severely debilitating, life-threatening genetic disorder caused by a deficiency of C1 inhibitor, a human plasma protein. This condition is the result of a defect in the gene controlling the synthesis of C1 inhibitor. C1 inhibitor maintains the natural regulation of the contact, complement, and fibrinolytic systems, that when left unrestricted, can initiate or perpetuate an attack by consuming the already low levels of endogenous C1 inhibitor in HAE patients. Patients with C1 inhibitor deficiency experience recurrent, unpredictable, debilitating, and potentially life threatening attacks of inflammation affecting the larynx, abdomen, face, extremities and urogenital tract. While there is no approved therapy for acute HAE attacks in the U.S., C1 inhibitor has been used in Europe to treat HAE for more than 35 years. There are estimated to be 10,000 people with HAE in the United States.

About Lev Pharmaceuticals, Inc.

Lev is a biopharmaceutical company focused on developing and commercializing therapeutic products for the treatment of inflammatory diseases. Lev’s lead product candidate, Cinryze™ (C1 inhibitor), is being developed as a replacement therapy for both the acute and prophylactic treatment of hereditary angioedema (HAE), also known as C1 inhibitor deficiency. Cinryze™ has been granted orphan drug status for the acute and prophylactic treatment of HAE, potentially securing, upon approval, market exclusivity for seven years. Additionally, Lev is in the process of prioritizing its C1 inhibitor development platform for the treatment of selective other diseases and disorders in which inflammation is known or believed to play an underlying role.
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[DewDiligence]

Half-Lives of the HAE C1-Inhibitor Contenders

There are three C1-inhibitor drug candidates vying for FDA approval in hereditary angiodema (HAE). All three are in the running for acute treatment of HAE attacks, but only one of them (Cinryze from LEVP) is in line for approval as a prophylactic.

The key distinguishing attribute is the half-life, which is shown below. (These numbers are means; there is considerable variation from patient to patient.)

Cinryze (LEVP): 48 hrs
Berinert (CSL Behring): 39.5 hrs
Rhucin (Pharming): 3 hrs

Discussion:

Rhucin is a recombinant drug produced in transgenic rabbits. As is the case with GTCB’s ATryn, Rhucin’s half-life is shorter than the corresponding endogenous protein due to differences in glycosylation. A short half-life is typically an advantage in an acute-care setting, but a half life of only three hours makes Rhucin totally unsuitable for prophylactic use.

LEVP is seeking approval of Cinryze as a prophylactic (#msg-28988139); the 48-hour half-life makes this doable insofar as patients can probably get by with two infusions per week.

Berinert’s 39.5-hour half-life is only about 20% shorter than the half-life of Cinryze. A 20% difference might not seem like a big deal on first glance, but it is a big deal because C1-inhibitors, as presently formulated, must be administered by IV and Berinert’s half-life would probably necessitate three infusions per week vs Cinryze’s two. Consequently, CSL Behring is not seeking FDA approval as a prophylactic.

Why does Berinert have a shorter half-life than Cinryze since they are the same protein and both are derived from human plasma? The difference in half-life probably stems from the processing to remove pathogens: Berinert uses pasteurization while Cinryze uses nano-filtration. Pasteurization presumably alters the C1-inh molecule in a way that speeds metabolism.

Sources:
http://www.transfusie.net/sanquin-eng/sqn_products_plasma.nsf/0/11343072be4286d2c125702a004a4e50/$FILE/Cetor%20SPC.pdf
http://tinyurl.com/57r4ch
http://www.ncbi.nlm.nih.gov/pubmed/16210064

[DewDiligence]

Jerini Hires Bank to Explore Sale

http://www.reuters.com/article/marketsNews/idINL034256920080603

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Tue Jun 3, 2008 12:21pm EDT
By Ben Hirschler and Mathieu Robbins

LONDON, June 3 (Reuters) - German biotech company Jerini (JI4G.DE) has hired Credit Suisse to explore strategic options, including a possible sale of the company, two sources familiar with the situation told Reuters on Tuesday.

Officials at Jerini and Credit Suisse declined to comment.

The move by Berlin-based Jerini to sound out buyers follows a spate of biotechnology deals on both sides of the Atlantic, in which large pharmaceutical companies have paid big premiums to secure promising assets in clinical development.

Shares in the group closed 18.7 percent higher at 2.60 euros following the news, valuing the business at around 136 million euros ($212 million).

Jerini's leading product is a drug called Icatibant, which was last month recommended for marketing approval by the European Medicines Agency but rejected by the U.S. Food and Drug Administration.

Icatibant is designed to treat acute attacks of hereditary angioedema (HAE), a rare disorder characterised by acute attacks of painful swelling in the hands, feet, face, larynx, and abdomen.

Jerini's share price was roiled in the wake of the mixed news from regulators, with some investors also concerned that the group may need additional funding to pay for the launch of Icatibant in Europe.

However, a third person familiar with the matter said there had been substantial interest in Jerini from German and U.S. companies following the European green light.

Icatibant is likely to go on sale in the third quarter and could generate annual revenues of more than $125 million a year by 2014 in Europe alone, according to a note published by Credit Suisse biotech analysts earlier on Tuesday.

It represents a niche product in a highly specialised sector of the market. Such drugs can command high prices, though the very limited number of patients suffering from HAE -- some 10,000 in the United States and Europe -- may mean Jerini appeals to a mid-sized rather than a large player, another source said.

U.S. drugmaker Abbott Laboratories (ABT) already has a stake of around 6 percent in Jerini [this comes from Kos Pharma, acquired by ABT, having once been Jerini’s development partner in HAE] alongside its two top shareholders, the venture capital groups HealthCap and TVM on 16.4 and 14.6 percent, respectively, according the company's website.

International consultancy Ernst & Young predicted recently that the convergence of the biotech and pharma industries would continue unabated in 2008, and leading drugmakers are continuing their shopping spree.

In the most recent big pharma-to-biotech deal, Bristol-Myers Squibb Co (BMY) agreed last week to buy cancer firm Kosan Biosciences Inc (KOSN) for $235 million -- a premium of 233 percent, though still below Kosan's year-ago share price peak.

Jerini was founded in 1992 by Chief Executive Jens Schneider-Mergener from a research group at what is now the joint medical faculty of the Humboldt Universitaet zu Berlin and the Freie Universitaet.

It went public in November 2005 and has a staff of 166.
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[DewDiligence]

Shire Acquires Jerini for $518M in Another High-Premium Deal

[The buyout premium relative to Jerini’s volume-weighted average price during the preceding three months is a whopping 199% (!); the premium relative to yesterday’s close is a not-too-shabby 71%. The deal is structured as a tender offer, but Shire already has more than a majority of the shares in the bag, so it’s a fait accompli.

The impetus for the deal is Firazyr (a.k.a. Icatibant) for HAE, which was approved by the EMEA and will be launched as soon as the EU Commission rubber stamps the decision (#msg-28772459). The FDA rejected Icatibant (#msg-28751487), but Shire may believe this decision can be reversed in due course.]

http://biz.yahoo.com/pz/080703/145774.html

›Thursday July 3, 4:08 am ET

Shire Offers Euro 6.25 Per Share and Further Subscribes For Shares in a Capital Increase

Takeover by Shire Ensures Successful Commercialization of Firazyr(r)

BERLIN, July 3, 2008 (PRIME NEWSWIRE) -- Jerini AG and Shire Limited today reached a strategic agreement according to which Shire shall be obliged to make a voluntary public takeover offer to all shareholders of Jerini AG. After a thorough evaluation of different strategic options, the Management Board of Jerini AG has concluded that Shire is the best partner with which it can further pursue and ensure the market introduction of Firazyr(r) (Icatibant) in Europe and obtain marketing approval in the United States.

The agreement regarding the strategic partnership provides for Shire to submit through Maia Elfte Vermogensverwaltungs-GmbH, to be renamed ``Shire Deutschland Investments GmbH', a voluntary public cash takeover offer at a price of Euro 6.25 per share to the shareholders of Jerini AG without a minimum acceptance threshold. The offer price corresponds to a premium of approximately 199 percent over the volume-weighted average stock price of Euro 2.09 of Jerini AG's shares during the three months prior to the announcement of the offer. The Management Board and the Supervisory Board of Jerini AG unanimously support the offer, which is contingent upon merger clearance and other customary conditions, subject to further assessment after the publication of the offer document. The Management Board believes that the offer price reflects the value of the shares upon the successful market introduction of Firazyr(r).

Management board of Jerini AG supports Shire's offer

``We are delighted to have found with Shire the right partner. Firazyr(r) will soon be available to HAE patients in Europe, and we are confident that Shire's commercial expertise will ensure its successful market introduction in Europe,' says Prof. Dr. Jens Schneider-Mergener, chairman of Jerini AG's Management Board.

``Jerini has successfully developed Firazyr(r), a first-in-class compound, which satisfies a high unmet medical need and treats a morbidly symptomatic disorder. With orphan designation in both Europe and the U.S., and a launch in Europe in the second half of this year, the acquisition will bring near term revenues as well as contribute to Shire's longer term growth,' said Angus Russell, Chief Executive of Shire.

In a first step, Shire has already subscribed for 5,229,747 shares of Jerini AG at a total issue price of approximately Euro 21 million, which corresponds to a participation of approximately 9percent of the increased share capital. The bidder has also entered into purchase agreements with the chairman of the Management Board Prof. Dr. Jens Schneider-Mergener, the Supervisory Board member Dr. Stephan Goetz and a number of major institutional shareholders, including TVM Capital Group and Healthcap Group, corresponding to approximately 53 percent of Jerini AG's share capital (prior to the capital increase).

Shire will undertake a strategic evaluation of the company's other assets, including its development projects, to determine which assets are compatible with its portfolio. Shire will then decide whether or not these should be integrated.

After a successful takeover and a transition phase, founder and CEO of Jerini AG, Prof. Dr. Jens Schneider-Mergener, and the other members of the Management Board will step down from their offices, but may consider to continue development projects in cooperation with the experienced Jerini team in a new company.

About Jerini AG

Jerini is a pharmaceutical company based in Berlin, Germany, focusing on the discovery, development, and commercialization of novel peptide-based drugs. Jerini develops drugs for disease indications that until now have limited or no treatment options. Alongside the development of its own compounds, Jerini cooperates with established partners. Jerini's lead drug, Firazyr(r), would be the first-in-class bradykinin blocker to be approved as a drug for the HAE and all European states. Its market introduction is planned for the third quarter of 2008. Jerini has also established several in-house development programs, which address indications within the therapeutic areas of ophthalmology, oncology and inflammatory disease. For more information, please see http://www.jerini.com.

About Shire Limited

Shire's strategic goal is to become the leading specialty biopharmaceutical company that focuses on meeting the needs of the specialist physician. Shire focuses its business on attention deficit and hyperactivity disorder (ADHD), human genetic therapies (HGT), gastrointestinal (GI) and renal diseases. The structure is sufficiently flexible to allow Shire to target new therapeutic areas to the extent opportunities arise through acquisitions. Shire's in-licensing, merger and acquisition efforts are focused on products in niche markets with strong intellectual property protection either in the U.S. or Europe. Shire believes that a carefully selected portfolio of products with strategically aligned and relatively small-scale sales forces will deliver strong results. For further information on Shire, please visit the Company's website: http://www.shire.com.

Credit Suisse are acting as advisers to Jerini AG and Deutsche Bank are acting as advisors to Shire Limited.‹


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