AsiaNet 65976

グルネンタール社の新しい強鎮痛剤セブラノパドール、第3相試験でがん性疼痛における有効性の主要評価項目を到達

試験結果を2016年IASP会議で発表

・がん性疼痛における統計学的に有意なデータが、変形性関節症、慢性腰痛および糖尿病性末梢神経障害による慢性疼痛の大規模ポジティブデータベースを強化

日本、横浜、2016年9月30日 - グルネンタール社は、自社化合物セブラノパドールのがん関連疼痛患者に対するデータを初めて発表します1。セブラノパドールのデータは、ランダム化、二重盲検、ダブルダミー、実薬対照反復投与第3相試験より得られたもので、患者はセブラノパドール1日1回投与群と、モルヒネ硫酸塩PR（持効性放出）1日2回投与群にランダムに割り付けられました。試験結果は、非劣性検証で統計学的有意を示し、さらには主要評価項目において優越性をも示しました（試験の維持期最後の2週間にわたる1日のレスキュー薬摂取平均量、p＜0.05）。セブラノパドールは忍容性が良好で、副作用はモルヒネ硫酸塩PRと同程度でした。この試験はこれまでにがん性疼痛を対象に実施された臨床試験では最大規模の試験の1つでしたが、戦略的な理由により患者登録は中止されました。グルネンタール社が発見・開発した新しいファースト・イン・クラスの鎮痛剤であるセブラノパドールは、これまでに中等度から重度の慢性神経障害性疼痛および筋骨格痛において明らかな有効性を示してきました。グルネンタール社は、セブラノパドールをアジアの患者が利用できるよう、開発および販売のパートナーを積極的に探しています。

グルネンタール社の最高科学責任者であるクラウス・ディーター・ラングナーは次のように述べています。「我々は、この有効で忍容性良好な医薬品を発見・開発してきたことを非常に誇りに思っています。さらに、セブラノパドールはその独自の作用機序(mechanism of action)、呼吸へ及ぼす影響を限定的にし得る改善された安全性プロファイル及び乱用可能性の低さから、他の強い鎮痛剤とは明確に差別化されます。セブラノパドールは、複数種類の慢性疼痛において多くのアンメットメディカルニーズに応えることができ、今回の新しいデータはがん性疼痛において同様にその可能性を示すものです。私たちは、米国地域を対象としたDepomed社との提携に続き、日本を含むアジア地域でのセブラノパドールの開発および販売に関心のある強力なパートナーを積極的に探しています。アジア地域でも、患者がセブラノパドールの恩恵を受けることができるようにするためです」

The full text of the release (English) can be downloaded at www.grunenthal.com

About cebranopadol

Cebranopadol is a novel, first-in-class analgesic that acts as a nociceptin/orphanin FQ peptide (NOP) receptor and opioid receptor agonist. These mechanisms, which have been shown to synergize, result in both a comparable efficacy and broader analgesic spectrum versus standard mu-opioid receptor agonists as well as an improved safety profile, particularly as it pertains to respiratory depression. In total, cebranopadol has been studied in approximately 2,000 patients worldwide having completed several Phase II trials in diabetic peripheral neuropathy (DPN), osteoarthritis (OA) and chronic low back pain (cLBP) and is ready for further Phase III development.

About Grunenthal

The Grunenthal Group is an independent, family-owned, international research-based pharmaceutical company headquartered in Aachen, Germany. We are an entrepreneurial specialist delivering true benefits to patients. By sustainably investing in research and development above the industrial average, we are committing to innovation in order to treat unmet medical needs and bring value-adding products to markets. Grunenthal is a fully integrated research & development company with a long track record of bringing innovative pain treatments and state-of-the-art technologies to patients.

Altogether, the Grunenthal Group is present in 32 countries with affiliates in Europe, Latin America and the US. Grunenthal products are sold in more than 155 countries and approx. 5,400 employees are working for the Grunenthal Group worldwide. In 2015, Grunenthal achieved revenues of EUR 1.2 bn. More information: www.grunenthal.com.

Literature

1 Cebranopadol, a novel first-in-class analgesic: Efficacy, safety, tolerability in patients with cancer related chronic pain (preliminary data). IASP2016, poster #116; abstract #3406. M Eerdekens, S Kapanadze, E Koch, G Kralidis, G Volkers, W Meibner

2 Cebranopadol, a novel potent analgesic nociceptin / orphanin FQ and opioid receptor agonist, induces limited respiratory depression at fully analgesic doses in rats due to the interaction of its nociceptin / orphanin FQ and opioid receptor agonist activities. IASP 2016, poster #3231. K Linz, S Frosch, W Schroeder, K Rutten, T Christoph

3 Cebranopadol, a novel first-in-class analgesic: Results from a study in patients with moderate to severe pain following bunionectomy. PAINWeek 2016, poster #N19. J Bothmer, A Scholz, K Hoschen, S Daniels

4 Cebranopadol, a Novel First-in-class Analgesic: Efficacy, Safety, Tolerability in Patients with Mixed Chronic Low Back Pain. PAINWeek 2016, poster #N23. A Christoph, M Eerdekens, M Kok, G Volkers, R Freynhagen

5 Cebranopadol, a Novel First-in-class Analgesic: Efficacy, Safety, Tolerability in Patients With Pain Due to Diabetic Peripheral Neuropathy. PAINWeek 2016, poster #N36. M Eerdekens, ED Koch, M Kok, M Sohns, T Forst

6 Cebranopadol: a Novel First-in-class Analgesic in Development for Chronic Pain Conditions - Results from a Human Abuse Potential Study in Non-Dependent Recreational Opioid Users. PAINWeek 2016, poster #N95. M Sokolowska, R Nemeth, E Babich, I Szeto, M Eerdekens

7 Cebranopadol: a Novel First-in-Class Analgesic in Development for Chronic Pain Conditions - Effects on Respiration in Healthy Human Volunteers. PAINWeek 2016, poster #N96. A Dahan, J Hay, GJ Groeneveld, M Neukirchen, J Bothmer, E Olofsen

Contact: Steffen Fritzsche, Head Corporate Communications

Tel.: +49 241 569-1335, Fax.: +49 241 569-51335, steffen.fritzsche@grunenthal.com

Grunenthal GmbH, 52099 Aachen, Germany, www.grunenthal.com

（日本語リリース：クライアント提供）

Grunenthal's cebranopadol, a Novel Strong Analgesic, Meets Primary Efficacy Endpoint in Phase 3 Trial in Cancer Pain

PR65976

YOKOHAMA, Japan, Sept. 30 /PRNewswire=KYODO JBN/ --

     Results to be presented at the 2016 IASP conference

    - Statistically significant data in cancer pain add to the large positive

database also in chronic pain due to osteoarthritis, chronic low back pain and

diabetic peripheral neuropathy

    Grunenthal presents data for the first time of its compound cebranopadol in

patients with cancer-related pain[1]. The cebranopadol data is from a Phase 3

randomized, double-blind, double-dummy, active-controlled multiple dose study

with patients randomized to either once-daily cebranopadol or twice-daily

morphine sulfate PR (prolonged release). Results reached statistical

significance for non-inferiority and even superiority for the primary endpoint

(average amount of daily rescue medication intake over the last two weeks of

the maintenance phase in the trial, p＜0.05). Cebranopadol was well tolerated,

with side effects comparable to morphine sulfate PR. Enrollment in this trial,

which is one of the largest trials conducted in cancer pain to date, was

stopped for strategic reasons. Cebranopadol, a novel first-in-class analgesic,

discovered and developed by Grunenthal, has previously demonstrated strong

efficacy in moderate to severe, chronic neuropathic pain and musculoskeletal

pain. Grunenthal is actively seeking for development and commercialization

partners to make cebranopadol available for patients in Asia.

    "We are very proud to have discovered and developed this effective, well

tolerated drug. Moreover, cebranopadol is clearly differentiated from other

strong analgesics by its unique mechanism of action, improved safety profile

with potentially limited effects on respiration and low abuse potential.

Cebranopadol addresses a high unmet medical need in several chronic pain types,

and these new data show its potential in patients with cancer pain as well,"

said Klaus-Dieter Langner, Chief Scientific Officer of Grunenthal. "Following

the partnership with Depomed for the US territory, we are actively looking for

a strong partner who is interested in developing and marketing cebranopadol in

the Asian region including Japan to ensure that also in this part of the world,

patients will be able to benefit from cebranopadol."

    Further, in-vivo data presented at IASP 2016 showed that the therapeutic

window between anti-nociception and respiratory depression is larger for

cebranopadol than for fentanyl, because the NOP receptor agonist action of

cebranopadol appears to counteract the side effects that result from its MOP

receptor agonist action[2]

    Data on cebranopadol presented at recently presented PAINWeek (6-9

September 2016, Las Vegas, USA) confirm its efficacy and safety

    Six abstracts reporting on efficacy and safety data from the cepranopadol

clinical development program were presented at the PAINWeek conference which

took place in Las Vegas, USA, in September 2016[3]-[7].

    Grunenthal has discovered and developed cebranopadol. While for the US

market, development and commercialization is established together with Depomed,

opportunities for partnering in Asia including Japan are still available.

    About cebranopadol

    Cebranopadol is a novel, first-in-class analgesic that acts as a

nociceptin/orphanin FQ peptide (NOP) receptor and opioid receptor agonist.

These mechanisms, which have been shown to synergize, result in both a

comparable efficacy and broader analgesic spectrum versus standard mu-opioid

receptor agonists as well as an improved safety profile, particularly as it

pertains to respiratory depression. In total, cebranopadol has been studied in

approximately 2,000 patients worldwide having completed several Phase II trials

in diabetic peripheral neuropathy (DPN), osteoarthritis (OA) and chronic low

back pain (cLBP) and is ready for further Phase III development.

    About Grunenthal

    The Grunenthal Group is an independent, family-owned, international

research-based pharmaceutical company headquartered in Aachen, Germany. We are

an entrepreneurial specialist delivering true benefits to patients. By

sustainably investing in research and development above the industrial average,

we are committing to innovation in order to treat unmet medical needs and bring

value-adding products to markets. Grunenthal is a fully integrated research &

development company with a long track record of bringing innovative pain

treatments and state-of-the-art technologies to patients.

    Altogether, the Grunenthal Group is present in 32 countries with affiliates

in Europe, Latin America and the US. Grunenthal products are sold in more than

155 countries and approx. 5,400 employees are working for the Grunenthal Group

worldwide. In 2015, Grunenthal achieved revenues of EUR 1.2 bn. More

information: http://www.grunenthal.com.

    Literature

    1 Cebranopadol, a novel first-in-class analgesic: Efficacy, safety,

tolerability in patients with cancer related chronic pain (preliminary data).

IASP2016, poster #116; abstract #3406. M Eerdekens, S Kapanadze, E Koch, G

Kralidis, G Volkers, W Meissner

    2 Cebranopadol, a novel potent analgesic nociceptin / orphanin FQ and

opioid receptor agonist, induces limited respiratory depression at fully

analgesic doses in rats due to the interaction of its nociceptin / orphanin FQ

and opioid receptor agonist activities. IASP 2016, poster #3231. K Linz, S

Frosch, W Schroeder, K Rutten, T Christoph

    3 Cebranopadol, a novel first-in-class analgesic: Results from a study in

patients with moderate to severe pain following bunionectomy. PAINWeek 2016,

poster #N19. J Bothmer,  A Scholz, K Hoschen, S Daniels

    4 Cebranopadol, a Novel First-in-class Analgesic: Efficacy, Safety,

Tolerability in Patients with Mixed Chronic Low Back Pain. PAINWeek 2016,

poster #N23. A Christoph, M Eerdekens, M Kok, G Volkers, R Freynhagen

    5 Cebranopadol, a Novel First-in-class Analgesic: Efficacy, Safety,

Tolerability in Patients With Pain Due to Diabetic Peripheral Neuropathy.

PAINWeek 2016, poster #N36. M Eerdekens, ED Koch, M Kok, M Sohns, T Forst

    6 Cebranopadol: a Novel First-in-class Analgesic in Development for Chronic

Pain Conditions - Results from a Human Abuse Potential Study in Non-Dependent

Recreational Opioid Users. PAINWeek 2016, poster #N95. M Sokolowska, R Nemeth,

E Babich, I Szeto, M Eerdekens

    7 Cebranopadol: a Novel First-in-Class Analgesic in Development for Chronic

Pain Conditions - Effects on Respiration in Healthy Human Volunteers. PAINWeek

2016, poster #N96. A Dahan, J Hay, GJ Groeneveld, M Neukirchen, J Bothmer, E

Olofsen

    Contact: Steffen Fritzsche, Head Corporate Communications     Tel.: +49 241

569-1335, Fax.: +49 241 569-51335, steffen.fritzsche@grunenthal.com

SOURCE: Grunenthal Group