REHOVOT, Israel—Kamada, one of Israel’s leading biopharma pioneers, has staked its success largely on the development of therapies for alpha-1 antitrypsin deficiency (AATD).
Founded in 1990, the publicly traded company is already known for Glassia®, an alpha-1 proteinase inhibitor and the first liquid plasma-derived product to treat AATD. Glassia was approved by the US Food and Drug Administration (FDA) in 2010, and, in 2016, the FDA approved an expanded label for it specifically allowing adults with emphysema due to severe AATD to self-infuse at home after appropriate training.
Now, Kamada is testing an inhaled product it says can potentially revolutionize the treatment of AATD.
“It’s a game-changer because a patient can sit in the comfort of their home and basically get a daily 10‑minute inhalation session instead of needing to go to a clinic for a weekly infusion,” Kamada CEO Amir London said. “In addition, because the inhaled product is much more effective in bringing the protein directly into the lungs, which are the target organ, we’ve shown in previous studies that it’s enough to give one-eighth the AAT dose compared to IV.”
London spoke to Rare Disease Advisor in an exclusive interview at Kamada headquarters in the Rehovot Science Park, a short walk from Israel’s famed Weizmann Institute of Science.
Kamada, with fiscal 2020 revenues of $133 million, is traded on the Tel Aviv Stock Exchange and NASDAQ. The company’s main raw material is human plasma, which it purifies into specific antibodies and proteins.
“Around 15 years ago, we decided that the alpha‑1 space is a highly unserved area with huge potential, so we focused our efforts on bringing the first liquid ready‑to‑infuse alpha‑1 product into the US market,” London explained. “The current standard of care [for AATD] is a weekly infusion, an augmentation treatment. Basically, they get the missing protein on a weekly basis.”
London said Kamada was also the only company to win FDA approval for self-infusion, “meaning that if a patient is independent enough, they can treat themselves at home without the need for a nurse or any support. Basically, this cut costs for the payers, and it’s another layer of convenience for the patients.”
AATD is extremely rare, yet it seems to be more prevalent in northern Europe—particularly Scandinavia, the Baltics, and the Iberian Peninsula. Immigration patterns over the centuries brought the inherited disease to the Western Hemisphere.
As a result, AATD is more common in Latin American countries like Argentina and Brazil, and less so in those with large indigenous populations such as Mexico and Bolivia. Almost no cases are seen in Asia or Africa, and in Israel, only a dozen or patients are being treated for the AATD.
“The disease is genetic. You are either alpha-1 deficient or a non-alpha-1 deficient patient,” London said. “The severity of the disease, and [whether] symptoms will even happen or not, really depends on your lifestyle and the way you live. If you smoke, God forbid, of course, you’re significantly increasing your likelihood of having symptoms.”
The US is believed to be home to an estimated 100,000 people who are alpha-1 deficient; Europe has a similar number. Yet only 8000 Americans and 3000 Europeans are currently being treated for AATD.
Read more about AATD epidemiology
“This is a highly misdiagnosed or undiagnosed disease, meaning less than 10% [of patients] are actually being treated currently for the disease,” he said. “The symptoms of alpha‑1 deficiency are identical to COPD, chronic obstructive pulmonary disease. That’s why in many cases, patients are being treated for COPD symptoms, but not treated for the underlying cause of the disease, which is the protein deficiency.”
London added: “If someone is alpha‑1 deficient, it’s very important that his or her siblings and kids be tested in order to see if they’re all deficient, lacking the protein . . . in order to prevent or mitigate the risk that they will suffer from symptoms.”
Kamada, with 400 employees, does all its research in Rehovot, though its products are manufactured at Kibbutz Beit Kama, the Negev Desert kibbutz where the company was founded (hence its name, a combination of Kama and “da”—the Hebrew word for knowledge).
Since 2015, total accumulated US sales of Glassia have reached around $350 million under a distribution agreement with Takeda. Glassia is also distributed in Israel, Argentina, Brazil, and Russia, and it’s under registration in several additional Latin American countries.
Besides Glassia, the company has a second FDA-approved drug called Kedrab, a human rabies immune globulin for the prophylactic treatment of people exposed to potentially rabid animals. Kamada has also completed a phase 1/2 clinical trial of its own hyperimmune globulin (IgG) therapy as a potential treatment for COVID-19 infection.
But the real prize is the global market for AAT treatments, expected to reach $1.8 billion annually by 2025, according to a Kamada information packet for potential investors.
At the moment, Kamada’s pivotal phase 3 trial, known as InnovAATe, is designed to test the safety and efficacy of inhaled AAT in up to 250 alpha-1 patients at selected sites throughout Europe and the United States.
According to Kamada, the double-blind, randomized study involves dosing 80 mg of inhaled AAT once a day or placebo over a 2-year period. The primary endpoint is lung function measured by FEV1 (the amount of air one can force from the lungs in 1 second), while the secondary endpoint is lung density changes measured by CT densitometry and other disease severity parameters.
“The COVID pandemic had its effect on delaying some progress,” London said, “but we are fully dedicated in taking this program forward, and hopefully being able in the future to bring this new treatment for the benefit of the alpha‑1 community.”