Trimbow(R) is the first triple combination in a single inhaler for the treatment of COPD to receive positive opinion from the CHMP in Europe

PARMA, ITALY—(Marketwired – May 20, 2017) –

  • Chiesi is the first pharmaceutical company to have demonstrated with randomized clinical trials, two of which published in The Lancet 1,2, the efficacy of the triple extrafine combination to prevent exacerbations, improve symptoms and quality of life.
  • Trimbow is the first fixed triple combination as extrafine formulation in a single inhaler that can improve adherence to the therapy.
  • CHMP positive opinion is based on data obtained in 12 clinical studies involving more than 7,000 patients.

Chiesi Group (Chiesi), an international research–focused healthcare company, announced today that the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion recommending marketing authorization for the extrafine triple combination ICS/LABA/LAMA, under the brand name Trimbow®, for the first time in a single inhaler for the treatment of Chronic Obstructive Pulmonary Disease (COPD).

Trimbow is a combination of Inhaled Corticosteroid (ICS) / Long–acting β2–agonist (LABA) / long–acting muscarinic antagonist (LAMA) that contains Beclometasone dipropionate (BDP), Formoterol fumarate (FF) and Glycopyrronium bromide (GB).

Paolo Chiesi, Chiesi Group Vice President and Head of R&D, said, “Today's positive opinion is an important step forward to make our extrafine Triple combination available to COPD patients. COPD affects millions of people across Europe, and Chiesi is committed to developing new therapeutic options that could help these patients' adherence to the therapy, thus reducing the risk of exacerbations and improving their quality of life. With this goal in mind, Chiesi has also developed the first fixed dose ICS/LABA/LAMA Triple combination.

Patients with COPD have unmet therapeutic needs, such as reducing the risk of exacerbations that impair the quality of life, which may lead to hospitalization or even be life–threatening 3–6. Indeed, the quality of life7 worsens when symptoms, such as dyspnoea and cough, are not controlled, and the patient needs to be hospitalized. Moreover, COPD is a disease that deteriorates with time8 and therapy often needs to be progressively intensified. This requires patients to be treated with many drugs that, to date, have to be taken through two or even three inhalers. The possibility of taking all drugs needed, and reaching both central and peripheral airways through only one inhaler considerably simplifies the treatment of COPD patients, decreasing the burden on patients and, thus, improving adherence.9,10

Therefore, a simplified treatment option based on ICS/LABA/LAMA that is able to improve lung function and reduce the risk of exacerbations in COPD patients, uncontrolled by previous therapies, would definitely satisfy those unmet needs.

The CHMP recommendation is based on the efficacy and safety data of 12 clinical studies involving more than 7,000 patients. Two of the studies were recently published by The Lancet — one of the most prestigious international medical journals:

  • TRILOGY1 is the study published in the special ERS edition of The Lancet and presented at the 2016 ERS Congress in London. The study provided for the first time, one year evidence that the extrafine fixed ICS/LABA/LAMA triple combination developed by Chiesi is superior to the fixed dose ICS/LABA combined therapy (one of the standard treatments for this condition) regarding a series of clinical parameters including exacerbations, and demonstrates a high safety profile.
  • TRINITY2, published in the online April 3 issue, is the study that has demonstrated for the first time the superiority of the extrafine ICS/LABA/LAMA triple fixed dose combination therapy, developed by Chiesi, compared to the LAMA tiotropium, one of the standard treatments for COPD, on a series of efficacy parameters including exacerbations.

The CHMP positive opinion is one of the final steps before the European Commission grants marketing authorization. A final decision by the European Commission and official grant of the marketing authorization is expected during the third quarter of 2017.

About COPD

COPD is a respiratory disease characterized by a persistent bronchial obstruction, associated with an increased chronic inflammatory response of the airways to noxious particles or gas. The classic symptoms associated with COPD are dyspnoea, chronic cough and chronic productive sputum. In some cases, an acute worsening of the above–mentioned symptoms may occur, triggering an exacerbation. A double mechanism is at work in the bronchial obstruction in COPD patients: on one hand, an inflammation of the small airways together with the thickening of the airways walls and increased airflow resistance may occur. On the other, a progressive destruction of lung parenchyma (emphysema) associated with the loss of elastic retraction of the lung may take place. It is important to underline that both mechanisms may coexist, leading to a significant airflow reduction throughout the lungs.

About Trimbow

Trimbow is the first extrafine fixed triple combination of Inhaled Corticosteroid (ICS) / Long–acting β2–agonist (LABA) / long–acting muscarinic antagonist (LAMA) that contains Beclometasone dipropionate (BDP), Formoterol fumarate (FF) and Glycopyrronium bromide (GB) Trimbow will be available as twice a day pMDI (pressurized metered dose inhaler) to be licensed for COPD indication, with an approved indication for maintenance treatment of COPD patients.

About Chiesi Group

Based in Parma, Italy, Chiesi Farmaceutici is an international research–focused Healthcare Group, with over 80 years of experience in the pharmaceutical industry, present in 26 countries. Chiesi researches, develops and markets innovative drugs in the respiratory therapeutics, specialist medicine and rare disease areas. Its R&D organization is headquartered in Parma (Italy), and integrated with 6 other key R&D groups in France, the USA, the UK, Sweden and Denmark to advance Chiesi's pre–clinical, clinical and registration programmes. Chiesi employs nearly 5,000 people. For more information please visit www.chiesi.com.

References

1 Singh D, Papi A, Corradi M, Montagna I, Francisco C, Cohuet G, Vezzoli S, Scuri M, and Vestbo J. Single inhaler triple therapy versus inhaled corticosteroid plus long–acting β2 agonist for chronic obstructive pulmonary disease (TRILOGY): a double–blind, parallel group, randomised controlled trial. Accepted (2016) THELANCET–D–16–04974R1;S0140–6736(16)31354–X.

2 Vestbo J, Papi A, Corradi M, Blazhko V, Montagna I, Francisco C, et al. Single inhaler extrafine triple therapy versus long–acting muscarinic antagonist therapy for chronic obstructive pulmonary disease (TRINITY): a double–blind, parallel group, randomised controlled trial. www.thelancet.com Published online April 3, 2017 http://dx.doi.org/10.1016/S0140–6736(17)30567–6.

3 Celli BR et al., An official American Thoracic Society/European Respiratory Society statement: research questions in COPD. Eur Respir J. 2015;45:879–905.

4 Progetto Libra 2010, Road Map BPCO, Rinite e Asma. www.goldcopd.it

5 Gard Italy: Sorveglianza nell'ambito delle patologie respiratorie, 25 giugno 2015.

6 Groenewegen KH, Schols AM, Wouters EF. Mortality and mortality–related factors after hospitalization for acute exacerbation of COPD. Chest. 2003;124:459–67.

7 Hernandez P, Balter M, Bourbeau J, Hodder R. Living with chronic obstructive pulmonary disease: A survey of patients' knowledge and attitudes. Respiratory Medicine. 2009;103:1004–12.

8 Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease, Progetto Mondiale BPCO, aggiornamento 2016 (www.goldcopd.org).

9 Stoloff SW, Stempel DA, Meyer J, et al. Improved refill persistence with fluticasone propionate and salmeterol in a single inhaler compared with other controller therapies. J Allergy Clin Immunol. 2004;113:245–51.

10 Nelson HS. Combination therapy of long–acting beta agonists and inhaled corticosteroids in the management of chronic asthma. Curr Allergy Asthma Rep. 2005;5:123–9.

Kashmir: Hard Choices Only

By Pervez Hoodbhoy
May 20 2017 (Dawn, Pakistan)

I recently received an extraordinary email from a troubled young Kashmiri in Srinagar. Days before the Indian authorities turned off the internet, Saif (not his real name) had watched on YouTube the 45-minute video documentary Crossing the Lines — Kashmir, Pakistan, India that I had helped make in 2004 and mostly agreed with its non-partisan narrative. A nationalist boy turned stone thrower, Saif is outraged by the brutality of Indian occupation. He is fortunate, he says. His 14-year-old second cousin lost his left eye to pellets.

Pervez Hoodbhoy

Pervez Hoodbhoy

Read: What pellet guns have done to protesters in Kashmir

Saif continues to fight India but is worried. Protesters of his father’s generation were largely nationalist, but today’s are a mixed bunch. IS and Pakistani flags are often unfurled after Friday prayers, azadi demonstrations resound with calls for an Islamic state in Kashmir, and Nasim Hijazi’s cartoon history of Muslim rule in India Aur Talwar Toot Gayee is serialised by local Urdu papers. Significantly, Burhan Wani was laid in the grave by a crowd of thousands, wrapped in a Pakistani flag, and celebrated as a martyr rather than Kashmiri freedom fighter.

Why this change? The present government — Narendra Modi’s — surely stands guilty. By reducing space for democratic discourse, it promotes radicalisation. Unlike Vajpayee’s accommodative politics, India offers little beyond the iron fist and draconian laws such as AFSPA. The BJP-PDP alliance — shaky to start with — is almost over as each blames the other for the two per cent voter turnout in last month’s by-elections. Hindutva’s religiosity is displacing Nehru’s secularism all across India, and Indian democracy is yielding to Hindu majoritarian rule.

Kashmiri nationalists must realise the grave dangers of giving more space to religious extremists.

But blaming Modi is half an explanation, perhaps even less. In Palestine, after decades of struggle against Israeli occupation, the secular PLO lost out to the religious radicalism of Hamas. In Arab countries, young Muslims dream of fighting infidels and dying as martyrs. In Pakistan, the celebrated army operations Raddul

Fasaad and Zarb-i-Azb target armed militants fighting for a Sharia state. Last week, the Higher Education Commission showed its concern by convening a meeting of 60 university vice chancellors in Islamabad on rising extremism in Pakistani campuses.

Extremism has further complicated an already complicated Kashmir situation. What now? For long, Kashmiris, Pakistanis, and Indians have wagged fingers at the other for the 100,000 lives lost over three decades. Where lies the future? Does any solution exist?

Read: Diary of a Kashmir curfew

A short retreat into mathematics: some equations indeed have solutions even if they need much effort. But other equations can logically be shown to have no solution – nothing will ever work for them. There is still a third type: that where solutions are possible but only under very specific conditions.

Kashmir is not of the first category. Everything has been tried. Delhi and Islamabad have created clients among the Valley’s leaders and political parties, and subversion is a widely used instrument. But they too have turned out to be useless. Elections and inducements have also failed to produce a decisive outcome, as have three Pakistan-India wars. A fourth war would likely be nuclear.

All parties stand guilty. India, under various Congress governments, had once projected itself as a secularist democracy distinct from an Islamic, military-dominated Pakistan. It appeared for that reason to be preferable, but in practice its unconscionable manipulation of Kashmiri politics led to the 1989 popular uprising, sparking an insurgency lasting into the early 2000s. When it ended 90,000 civilians, militants, police, and soldiers had been killed. Remembered by Kashmiri Muslims for his role in the 1990 Gawkadal bridge massacre, Governor Jagmohan received the Padma Vibhushan last year.

Pakistan tried to translate India’s losses into its gains but failed. It soon hijacked the indigenous uprising but the excesses committed by Pakistan-based mujahideen eclipsed those of Indian security forces. The massacres of Kashmiri Pandits, targeting of civilians accused of collaborating with India, destruction of cinema houses and liquor shops, forcing of women into the veil, and revival of Shia-Sunni disputes, severely undermined the legitimacy of the Kashmiri freedom movement.

Pakistan’s ‘bleed India with a thousand cuts’ policy is in a shambles today and jihad is an ugly word in the world’s political lexicon. Say what you will about ‘Dawn Leaks’, but Pakistani diplomats who represent Pakistan’s position in the world’s capitals know the world doesn’t care about Kashmir. How else to explain Prime Minister Modi receiving Saudi Arabia’s highest civilian award from King Salman bin Abdul Aziz?

If Kashmir is ever to have a solution — ie belong to the third type of math problem — then all three contenders will need to rethink their present positions.

Thoughtful Indians must understand that cooling Kashmir lies in India’s hands, not Pakistan’s. By formally acknowledging Kashmir as a problem that needs a political solution, using humane methods of crowd control, and releasing political prisoners from Kashmiri jails, India could move sensibly towards a lessening of internal tensions. Surely, if India considers Kashmiris to be its citizens then it must treat them as such, not as traitors deserving bullets. Else it should hand Kashmir over to Kashmiris — or Pakistan.

Thoughtful Pakistanis must realise that their country’s Kashmir-first policy has brought nothing but misery all around. Using proxies has proven disastrous. A partial realisation has led to detaining of LeT and JeM leaders, but Pakistan’s army must crack down upon all Kashmir-oriented militant groups that still have a presence on Pakistani soil. Such groups are a menace to Pakistan’s society and armed forces, apart from taking legitimacy away from those fighting Indian rule.

Thoughtful Kashmiri nationalists — like Saif — must recognise the grave dangers of giving more space to religious extremists. Their struggle should be for some form of pluralistic entity – whether independent or under nominal Indian or Pakistani control. That entity must assure personal and religious freedoms. An ISIS type state with its cruel practices makes mockery of the very idea of azadi and would pave the way for Kashmir’s descent into hell.

Such rethinking would clear the road to peace through negotiations which, though narrowed, still remains open. Every conflict in history, no matter how bitter, has ultimately been resolved. In Kashmir’s case whether this happens peacefully, or after some apocalypse, cannot be predicted.

The author teaches mathematics and physics in Lahore and Islamabad.
Published in Dawn, May 20th, 2017

This story was originally published by Dawn, Pakistan