Takeda, “Alunbrig improved both OS and QoL”

Bokyung Kim, Medical Science Liaison at Takeda Pharmaceuticals Korea

Enters market as the third 2nd generation ALK TKI…despite being a latecomer, makes way into market fast approved as 1st line with reimbursement

Independent review committee assessment… “significant effect in patients with brain metastasis”

Demonstrated improvement in quality of life in younger patients…holds strength with its convenience in administration

Medical Science Liaisons (MSLs) in Medical Affairs of pharmaceutical companies act as a ‘bridge’ between healthcare professionals and companies.

 

They gather the unmet needs of HCPs and establish strategies for new drugs to address such needs.

 

MSLs also deliver academic data and expertise based on clinical grounds in compliance with local regulations to HCPs, patients, and internal employees.

 

Competition has been fierce in the non-small cell lung cancer treatment market, particularly the ALK targeted therapy market, with the introduction of various new drugs.

 

The market is moving on from the one-and-only 1st generation treatment, Pfizer’s ‘Xalkori,’ to 2nd generation products.

 

By order of entry, three 2nd gen products - Novartis’s ‘Zykadia (ceritinib),’ Roche’s ‘Alecensa (alectinib),’ and Takeda Pharmaceutical’s ‘Alunbrig (brigatinib)’ – have entered the market.

 

Among these, Roche and Takeda’s products are in the fiercest competition.

 

The role and responsibility of MSLs in charge of these products have also increased.

 

Dailypharm met with Bokyung Kim, MSL at Takeda Pharmaceuticals Korea’s to hear about the ALK-positive NSCLC treatment market, its unmet needs, and the role and strategy of Alunbrig in this market.

 

Bokyung Kim, MSL at Takeda Pharmaceuticals Korea

-Could you give us a brief introduction about yourself and your role in Medical Affairs of Takeda Pharmaceuticals Korea? = SInce entering Takeda Pharmaceuticals Korea as an MSL in October last year, I have been in charge of Alunbrig for 9 months.

 

I meet with healthcare professionals to identify the unmet needs in the field to establish strategies based on the demand.

 

In the company, I discuss with various business divisions to set the direction for Alunbrig and prepare the necessary medical grounds so that our drug can contribute to resolving the unmet needs in the field.

 

In the past, the Medical Affairs division mainly performed tasks to support other business divisions in the company, however, perception of the role of our department has started to change around 10 years ago.

 

Medical Affairs now develops core strategies for new drugs, serving as a bridge between various business units as well as research and development.

 

Also, the unit provides academic data and expertise to internal and external stakeholders in an objective and fair manner in compliance with the local code of medical ethics and regulations and provides academic advice.

 

-At the time Alunbrig was introduced to Korea, other ALK-targeted therapies were already in the domestic market.

 

Were there any difficulties due to this late entry? =Other treatments that were released before Alunbrig have brought treatment benefits to patients, however, unmet needs still existed in various areas, ranging from treatment effect, adverse events, quality of life, to convenience in administration.

 

I believed that the introduction of Alunbrig could bring new treatment benefits that existing treatments were unable to provide.

 

-What unmet need still remains due to characteristics of ALK-positive NSCLC in Korea?

 

=ALK mutation occurs in around 4-5% of all NSCLC patients and occurs more commonly in women and Asian patients.

 

Also, it is found more frequently in non-smokers compared to other NSCLCs and affects a relatively younger population in their 50s to 60s.

 

Therefore, in addition to data on survival such as progression-free survival (PFS), other factors such as tolerance, medication adherence, and quality of life should also need to be considered collectively.

 

The biggest unmet need in the treatment of ALK-positive NSCLC lies in brain metastasis and tolerance.

 

This patient population has a higher risk of brain metastasis than other lung cancer patients.

 

How long a drug can delay brain metastasis, and how effective the drug is in patients with brain metastasis must be considered.

 

Also, people may have developed tolerance to TKI targeted drugs, therefore, how effective the drug is in such a population is also an important consideration.

 

-With Alunbrig approved for insurance benefit in April as a 1st-line therapy, all ALK-targeted drugs introduced to Korea are now available with reimbursement from 1st line.

 

What strengths does Alunbrig have over other ALK-targeted therapies with regards to its mechanism of action?

 

How effective was the drug in patients with brain metastasis in clinical trials? =Unlike other existing treatments, Alunbrig was developed into a unique U-shaped platform.

 

This structural design allows the drug to bind more strongly to the ATP attachment site that is used as an energy source when activating the ALK gene.

 

In a preclinical trial, the drug selectively bound to ALK mutant variants to act stably in the body.

 

Furthermore, Alunbrig demonstrated superior progression-free survival (PFS) and improved health-related quality of life (QoL) versus Xalkori, the existing first-line treatment option, in the Phase III ALTA-1L trial.

 

In particular, in the second interim analysis, Alunbrig demonstrated superior clinical efficacy over Xalkori in the first-line setting regardless of brain metastasis in all ALK-positive NSCLC patients.

 

Also, Alunbrig demonstrated a differentiated PFS improvement compared to Xalkori from early on in patients with brain metastasis that are difficult to treat.

 

In addition, Alunbrig significantly reduced HR compared to Xalkori, to 0.25.

 

So far, the data presented from the ALTA-1L trial only covers up to a two-year follow-up study by June 28th of 2019.

 

We expect to see longer survival data when the final results are released soon.

 

-Compared to other drugs that conducted investigator-assessed trials, the ALTA-1L trial was designed closer to the real world with BIRC-assessed endpoints.

 

Why did the study choose to use BRIC-assessed results, which would have brought out more conservative results? =According to FDA guidelines, review from an independent evaluation committee can minimize bias.

 

This is not essential in randomized, blinded clinical trials, however, as chemotherapy is often the standard treatment in cancer treatment, comparing this with oral anticancer drugs in a blinded trial is realistically not possible.

 

This is why the trials are designed as open-label trials, in which case, BIRC assessment is required.

 

We used BIRC-assessed primary endpoints according to the guideline recommended by the FDA to increase the objectivity and fairness of our trial.

 

-How does Alunbrig affect patients with regards to their quality of life?

 

= ALK-positive NSCLC occurs commonly in the socially active 50s.

 

Therefore, studies on Alunbrig assessed the improvement in quality of life in addition to the drug’s efficacy.

 

Assessed with the representative tool used for quality of life in cancer patients, EORTC QLQ-C30, the Alunbrig arm maintained the quality of life without worsening for 26.7 months vs.

 

Xalkori.

 

Also, convenience in administration is also an important factor to consider in long-term treatment.

 

Many studies on long-term treatment experience from chronic diseases among others have shown that convenience in administration is very important for the quality of life and prognosis of patients.

 

Alunbrig’s 1 tablet once daily administration is expected to contribute to the improvement of quality of life in these patients.

 

*Dose and schedule of first-generation Xalkori is 1 tablet taken twice daily.

 

Zykadia is taken in 3 capsules once daily, and Alecensa is taken in 4 capsules twice daily.

 

-How was Alunbrig received in the field after being approved for reimbursement as first-line?

 

Some have said that Alunbrig and Alecensa have similar efficacy in patients with brain metastasis.

 

What is your view on this? =Alunbrig was positively reviewed by HCPs since being reimbursed as second-line treatment due to its good treatment effect in patients.

 

With its reimbursement expanded in April, doctors have highly rated the drug as a new treatment opportunity for patients with an unmet need and for those who saw unsatisfactory effects from existing first-line therapies.

 

Expectations were high as Alunbrig had shown high clinical effects in patients, but they were also highly satisfied in terms of convenience in administration.

 

Also, the company’s efforts to promptly approve and reimburse Alunbrig in Korea as soon as it was approved as a first-line in the U.S.

 

were positively received.

 

Alunbrig and Alecensa have both shown better effects than Xalkori in clinical trials on patients with brain metastasis.

 

We cannot directly compare the two drugs due to a lack of head-to-head study, however, patients should consider various aspects in addition to treatment effect, such as tolerance and convenience in administration when selecting their treatment.

 

-Some patients hesitate using Alunbrig due to its pneumonia adverse reaction. =In the field, clinical practitioners have deemed that the symptoms after administering Alunbrig were similar to pneumonia, but is an EOPE (Early-Onset Pulmonary Events) that occurs temporarily.

 

In some patients, symptoms similar to pneumonia may appear temporarily, but when the symptom is resolved early on, the symptom has the characteristic of not occurring again during the period of administration.

 

Also, clinical experts in Korea have also said that EOPE symptoms are reversible adverse reactions that are fully manageable and can be quickly recovered.