Leaders in Pharmaceutical Business Intelligence (LPBI) Group

Alpha-1 Antitrypsin Deficiency: Treatment by Inhaled Drug for the Protein Deficiency linked to an Increased Risk of Lung and Liver Disease – Failing Phase II/III Clinical Trials

Reporter: Aviva Lev-Ari, PhD, RN

Israeli biotech Kamada ($KMDA) confirmed that its lead candidate failed to meet both its primary and secondary endpoints in a late-stage trial–but that won’t interrupt the company’s plans to file for European approval. Investors didn’t seem to share management’s optimism, however, sending Kamada’s shares down about 20% on Thursday morning.

Kamada’s drug is designed to treat a protein deficiency linked to an increased risk of lung and liver disease, replacing patients’ missing alpha-1 antitrypsin (AAT) through an inhaled treatment. Back in May, the biotech revealed that its drug failed to beat out placebo in its primary goal of delaying flare-ups in lung conditions in a Phase II/III trial on 168 patients. Now, confirming those results, Kamada adds that AAT didn’t come through on its secondary endpoints, either.

However, the drug “showed concordance of a potential treatment effect” on lung function, the company said, especially in a subgroup of patients most prone to exacerbations. A few of those measurements even hit statistical significance, according to Kamada, and the company’s inhaled AAT proved safe and tolerable in the study.

So, despite the missed efficacy endpoints, Kamada is planning to press ahead with regulatory filings, pointing out that existing intravenous treatments for AAT won approvals on the strength of safety data alone. And, CEO David Tsur contends, those positive signals among the most severe patients demonstrate the promise of Kamada’s drug in an underserved population.

“Based on orphan designation of the drug, prior discussions held with the regulator, the strength of these data and the persistent unmet need in this orphan indication, we will advance our discussions with the European Medicines Agency with the intent to submit for conditional approval in order to bring our inhaled AAT to patients with AATD in Europe, and will initiate discussion with the FDA to determine a U.S. path for registration,” Tsur said in a statement.

That wasn’t enough to satisfy Wall Street, however, and AAT’s latest misstep sent Kamada’s shares down to around $5.75, nearly 40% below its 2013 IPO price of $9.25 and well off its March peak of $17.50.

Meanwhile, Kamada is in the midst of a Phase II trial on AAT, results from which the company plans to combine with the Phase II/III to support its FDA application. Italy’s Chiesi Farmaceutici has signed up to commercialize the drug in Europe if it wins approval, a deal that could mean up to $60 million for Kamada.

Alpha-1 antitrypsin deficiency affects between one in every 1,600 people and one in every 5,000 people, according to the National Institutes of Health.

Alpha-1 Antitrypsin Deficiency

Alpha-1 antitrypsin, also called AAT, is a protein made in the liver. Normally the protein travels through the bloodstream and helps protect the body’s organs from the harmful effects of other proteins. The lungs are one of the main organs that the AAT protein protects. AAT deficiency (AATD or inherited emphysema) occurs if the AAT proteins made in the liver are not the right shape, and they get stuck inside liver cells and cannot get into the bloodstream. As a result, not enough AAT proteins travel to the lungs to protect them, which increase the risk of lung disease. Also, liver disease can develop because too many AAT proteins are stuck in the liver. Severe AATD occurs when blood levels of the AAT protein fall below the lowest amount needed to protect the lungs.

AATD is an inherited condition that occurs in all ethnic populations, yet most often in Caucasians of European descent. It is not known how many people have AAT deficiency and many people who have the condition may not know they have it. According to the National Institutes of Health, estimates of disease incidence range from about 1 in every 1,600 people to about 1 in every 5,000 people.

About eFlow® Technology and PARI Pharma

The Company’s inhaled AAT is delivered by an investigational eFlow® Nebulizer System developed by PARI Pharma and optimized specifically for Kamada. The optimized device uses eFlow Technology to enable highly efficient aerosolization of medication including liposomal formulations via a vibrating, perforated membrane that includes thousands of laser-drilled holes. Compared with other nebulization technologies, eFlow Technology produces aerosols with a very high density of active drug, a precisely defined droplet size and a high proportion of respirable droplets delivered in the shortest possible period of time. eFlow Technology is not an ultrasonic nebulizer technology and is not a general purpose electronic aerosol generator nebulizer technology. Combined with its quiet mode of operation, small size, light weight and battery use, eFlow Technology reduces the burden of taking daily, inhaled treatments.

About Chiesi Farmaceutici

Chiesi Farmaceutici is a research-focused international group, with nearly 80 years of experience headquartered in Parma (Italy). Chiesi researches, develops and commercializes innovative pharmaceutical solutions in the respiratory therapeutics, specialist medicine and rare diseases areas. In 2013, Chiesi achieved sales of over 1.2 billion Euros, constituting double digit growth over 2012. Its R&D centers in Parma (Italy), Paris (France), Rockville (USA), Chippenham (UK) and the R&D team of the newly-acquired Danish company Zymenex, integrate their efforts to advance Chiesi’s pre-clinical, clinical and registration programs. The Chiesi Group employs approximately 3900 people, 480 of which are dedicated to R&D activities.

For more information, please visit www.chiesi.com

About Kamada

Kamada Ltd. is focused on plasma-derived protein therapeutics for orphan indications, and has a commercial product portfolio and a robust late-stage product pipeline. The Company uses its proprietary platform technology and know-how for the extraction and purification of proteins from human plasma to produce Alpha-1 Antitrypsin (AAT) in a highly-purified, liquid form, as well as other plasma-derived proteins. AAT is a protein derived from human plasma with known and newly-discovered therapeutic roles given its immunomodulatory, anti-inflammatory, tissue-protective and antimicrobial properties. The Company’s flagship product is Glassia®, the first and only liquid, ready-to-use, intravenous plasma-derived AAT product approved by the U.S. Food and Drug Administration. Kamada markets Glassia in the U.S. through a strategic partnership with Baxter International. In addition to Glassia, Kamada has a product line of nine other pharmaceutical products that are marketed through distributors in more than 15 countries, including Israel, Russia, Brazil, India and other countries in Latin America, Eastern Europe and Asia. Kamada has five late-stage plasma-derived protein products in development, including an inhaled formulation of AAT for the treatment of AAT deficiency that completed a pivotal Phase 2/3 clinical trial in Europe and has initiated Phase II clinical trials in the U.S. Kamada also leverages its expertise and presence in the plasma-derived protein therapeutics market by distributing 10 complementary products in Israel that are manufactured by third parties.