인슐린 잔혹사 – 끝날까?

오늘 FierceBiotech에서 흡입식 인슐린인 Alfrezza (2014년 6월 27일 FDA허가 받음)의 판권 계약을 했다는 뉴스가 나왔다.  기사를 보면 아래와 같다. (http://www.fiercebiotech.com/story/sanofi-fills-some-big-shoes-925m-afrezza-pact-mannkind/2014-08-11

MannKind finally wins an FDA OK for inhaled insulin Afrezza. Now what?

MannKind CEO Al Mann

Three years and hundreds of millions of dollars after MannKind was handed its second FDA rejection onAfrezza, the third time proved the charm for the inhaled insulin. The FDA on Friday handed out its blessing for MannKind ($MNKD) to start marketing the drug, which will now set out to see if it can succeed with an inhaled insulin after Pfizer’s ($PFE) Exubera failed so spectacularly at the task.

The market is huge. Some 26 million Americans have Type 2 diabetes, threatened by high levels of blood sugar. Valencia, CA-based MannKind–cheered, chaired and financed to a large degree by Al Mann–has long believed that its inhaled insulin offered an easier way for many of those people to control the disease. But after Pfizer had failed to make a go of it, potential major league partners kept their distance, forcing the biotech to dig deep–and borrow more–to finish the last two Phase III studies.

“Afrezza is a new treatment option for patients with diabetes requiring mealtime insulin,” said Jean-Marc Guettier, M.D., director of the Division of Metabolism and Endocrinology Products in the FDA’s Center for Drug Evaluation and Research. “Today’s approval broadens the options available for delivering mealtime insulin in the overall management of patients with diabetes who require it to control blood sugar levels.”

This 3-part webinar series is specifically geared toward the non-science professional who needs to better understand industry terminology, science, techniques and issues. This series provides an overview of the science and technology used to enable discovery and the processes scientists use to discover new therapeutics. Register Now!

Afrezza has been under FDA review off and on for the past 5 years and was rejected for a second time in 2011 after the company switched inhalers while it was under consideration. The writing on the wall for Afrezza finally looked good for the biotech following an overwhelmingly positive FDA panel vote on April 1. The outside experts clearly felt that investigators had provided a positive look at the risk/benefit profile of the treatment. The vote in its favor came despite an internal FDA review that raised fresh questions about risks of bronchial spasms, an impact on lung function as well as the efficacy data on Type 1 patients.

MannKind’s Afrezza is delivered through a whistle-shaped inhaler called Dreamboat.–Courtesy of MannKind

The FDA noted in its release that Type 1 diabetics who use Afrezza will need to continue to use a long-acting insulin. The agency also laid out a risk mitigation plan and requirements for a slate of post-marketing studies to examine risk as well as patients’ reactions to the therapy.

Afrezza will carry a label with a boxed warning of acute bronchospasm for patients with chronic lung disease, the risk of hypoglycemia, a decline in pulmonary function, and other potential reactions,

Skeptics have focused plenty of negative attention on MannKind over the years. But back in 2011, MannKind borrowed $370 million to rerun the inhaled drug in Phase III. The same skeptics, though, have downplayed this dry powder’s ability to compete against well established injectables, especially after much bigger companies have tried and failed before.

Pfizer pulled Exubera from the market back in 2007, a little more than a year after the agency handed out its endorsement, Jinxed by a high price and hard-to-use inhaler, patients stayed away in droves and predictions of certain blockbuster status had quickly evaporated.

MannKind’s response, though, is that Afrezza’s formulation and inhaler is different than its predecessors. Now it will have to prove itself all over again. Analysts estimate the treatment should be able to earn about $600 million a year. MannKind’s shares slipped about 6% at the close today.

“Approval of Afrezza is an important milestone for MannKind, as today’s FDA action validates the years of clinical research and commitment that powered the development of this unique therapy,” said Mann in a statement.

 

우선 뉴스를 보고 웃어야 할지 울어야 할지 모르겠다.

바로 인슐린 관련 잔혹사들 때문이다. 

가장 큰 잔혹사는 2007년 Pfizer-Nektar 이다.

Nektar Therapeutics라는 회사는 1990년도에 San Francisco에서 설립된 회사로 초기 이름은 Inhaled Therapeutics였다.  1996년 Pfizer와  인슐린의 흡입형 제품을 만들기로 연구계약을 하고 그로부터 10년 지난 2006년 1월 27일  FDA의 허가를 받았다. Exubera라는 이름으로….

Nektar의 기술은 단백질에 PEG을 붙인 후 가공을 통해 단백질을 파우더 분말 형태로 만든 후 흡입기(Inhaler)에 넣고 폐로 넣어주는 것이다.

하지만 처참하게도 2007년 매출이 고작 12백만불밖에 되지 않자 Pfizer는 제품을 그야말로 버려버렸다.  (http://online.wsj.com/news/articles/SB119269071993163273)

당시 Wall Street Journal의 설명을 참고하면 Pfizer가 Exubera에 쏟아 부은 $2.8 Billion… 물론 세금 효과를 고려하면 이보다는 작겠지만….

아마 순투입액으로 보면 아마 제약 역사상 최대 규모의 폭탄이었을 것이다.

필자가 1998년 Pfizer들과 만날 때 들은 이야기는 분말 인슐린 중 실제 폐조직을 통해 인체에 흡수되는 생체이용률(bioavailability)는 대략 10% 정도….

 

 

오늘  Sanofi와 계약을 체결한 MannKind도 잔혹사라고 한다면 만만치 않은 이야기이다.

이번 6월에 허가 받은 것이 그야말로 삼수로 얻은 감격적인 합격이기 때문이다. FDA에 NDA 두번 넣었는데 떨어지고, 세번째에서 허가를 받은 것이다.

의지의 한국인만 있는게 아니고 의지의 미국인도 있다. Alfred Mann  이름에서 알겠지만 MannKind의 실질적인 주인이다. 회사에 부은 개인의 돈만 9억불….

회사의 시가총액이 32억불이고 Mr. Mann의 지분율이 약 47%이니 가치로 치면 손해본게 없지만…. 이제 exit을 해야 하니…

그런데 이번 Sanofi와의 계약을 보면 정말 눈물난다.

제품허가를 받은 흡입형 인슐린에 대한 판권인데 고작 1.2억불… 어찌보면 좀 굴욕스러운 upfront payment이다.

다른 회사들이 인슐린의 흡입형에 별로 관심이 없다는 것이다.

 

이유를 몇가지 들면 아래와 같다.

1) 가격적인 부담

2) 과량의 인슐린 (엄연한 호르몬)이 지속적으로 기도와 폐 조직에 노출될 경우의 잠재적인 위험성

 

아마 2번째 요인은 내분비과 의사라면 당연히 걱정할 사항이다.

장점도 있다. 피하주사에 비해 훨씬 빠른 속도로 효과를 낸다. 내략 몇십분 내외.

 

Sanofi가 과연 흡입형 인슐린의 잔혹사에 끝을 낼까… 아니면 잔혹사의 또다른 에피소드를 제공해 줄까?

Advertisements

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s