Capmatinib: The Race to Approval and Optimal Pricing
By Ines Dieringer – Associate Consultant
With new mutations which are driving oncogenesis in life-threatening cancers being discovered everyday, the industry looks be keeping pace with targeted therapies for these mutagenic targets. One such example is Novartis’ investigational therapy Capmatinib. This investigational therapy Is targeted at MET exon 14 skipping (METex14) mutated advanced non-small cell lung cancer (NSCLC) in first-line.
In light of recent developments,the FDA has decided to fast-track its regulatory review for Novartis’ Capmatinib for the treatment of an aggressive form of Non-Small Cell Lung Cancer (NSCLC) known for having a substandard prognosis. This priority review will shorten the FDA’s review process from 10 to 6 months, and is a type of review usually reserved for medicines that could significantly improve the treatment and management of diseases. Capmatinib is being marketed as a treatment for locally advanced or metastatic METex14-mutated NSCLC. There are currently no therapies on the market that treat this form of mutation, and since it affects nearly 3% to 4% of NSCLC cases, finding a suitable treatment is critical.
|Figure 1 – Results from the GEOMETRY study examining the safety and efficacy of Capmatinib indicated for MET-mutated NSCLC|
Capmatinib is supported by positive data from the Phase II GEOMETRY study studying Capmatinib as a single agent in the treatment of adult patients with advanced NSCLC with an existing MET mutation. This assessment reports in its efficacy analysis on both treatment-naïve and previously treated population the following results:
The most common adverse events were peripheral oedema, nausea, creatinine increase, vomiting, fatigue, decreased appetite, and diarrhoea, with very few of them being considered severe adverse events2.
The ongoing study NCT02414139, an international, multi-cohort, open-label study further evaluates the safety and efficacy of Capmatinib as monotherapy in the adult population, as a first-line and 2nd/3rd line treatment. This study will provide further, more in-depth data on the safety and efficacy of Capmatinib and is expected to be completed on May 10, 2021.
While Novartis has made significant progress in developing an MET inhibitor, it is not the only company with their eyes set on being the first to introduce this therapy into the market. Merck’s Tepotinib, which also aims to target MET mutations, received the designation of Breakthrough Therapy by the FDA last September and was also granted fast-track designation in Japan. The ongoing VISION study, a Phase II clinical trial analysing Tepotinib as a monotherapy for the treatment of MET-mutated NSCLC with patients being diagnosed through either liquid or tissue biopsy showed a response rate of between 45-50% in all patients.
The priority review awarded to Novartis gives the company an advantageous position in the NSCLC landscape despite Merck’s impressive results in the same indication. If Capmatinib is the first to reach the market, it could become eligible for over $500 million in milestone payments as well as royalties of around 14% of global sales by Novartis5.
Both companies are also aiming to expand their asset’s indication to EGFR-mutated NSCLC after EGFR inhibitor treatment failure, with Novartis testing Capmatinib against Iressa and Merck comparing Tepotinib against Tagrisso5. MET mutations are known for causing a wide variety of cancers including EGFR resistant NSCLC, gastric carcinomas, oesophageal carcinoma, liver metastases, medulloblastoma or breast cancer. MET inhibitors may therefore prove to be a very versatile therapy that can be used to treat a wide array of cancers not limited to just NSCLC variations.
In order to visualise the impact of introducing the first MET-inhibitor could have on the oncology market, we have analysed trends shown by the previous significant gene mutation inhibitor: EGFR. The figure below provides a timeline of the initial FDA approval of the most notable treatments indicated for the treatment of EGFR-based NSCLC.
|Figure 2 – Timeline of FDA approvals of EGFR-indicated treatments|
Iressa was the first EGFR inhibitor to be approved by the FDA and received priority review status. After its initial approval in 2005, there was a 15-year gap until the second EGFR inhibitor, Portrazza, was approved. In the meantime, other drugs began to receive FDA approvals to target EGFR-mutated NSCLC through different pathways. Tarceva, approved only one year after Iressa, inhibited the enzyme tyrosine kinase (TK) to treat EGFR NSCLC. Once again, there was a significant time gap between Tarceva and the next TK inhibitor to be approved, with Gilotrif being approved nine years after Tarceva’s approval. Furthermore, after Gilotrif’s approval, there was a significant influx of drugs targeting EGFR mutations into the market with Cyramza, Keytruda, Opdivo, Tagrisso, and Portrazza being approved within two years. This timeline suggests that after the initial approval of two significant medicines targeting EGFR mutations, there was a considerable time gap until additional medications were approved, after which the remedies mentioned above entered the market, giving enough time for the manufactures to capitalize on their initial investment.
While we can expect the gap between MET inhibitor approvals to be smaller than that of EGFR inhibitors, due to Merck also having Tepotinib in the pipeline, it may be safe to assume that the two MET inhibitors may be released within a similar timeframe as Iressa and Tarceva and could then experience the same gap until other drugs are introduced into the market. This highlights the importance of reaching this market early to gain a significant amount of market share for as long as possible.
This timeline also shows that several very versatile (Opdivo and Keytruda) medicines have been approved for EGFR-mutated NSCLC as one of their many indications. While this means that there are always novel ways of targeting different types of NSCLC, it also raises interesting points about the current MET inhibitors being developed. Both Novartis and Merck are conducting studies to expand their asset to EGFR-mutated, cMET-amplified NSCLC after EGFR-inhibitor treatment failure. Assuming Capmatinib can gain the aforementioned indication approvals in different forms of NSCLC, and could gain additional indication approvals for other forms of cancer, this medicine could have a very profitable outcome, matching that of other known versatile medicines. To illustrate this point, we have analysed the price evolution of Opdivo, Keytruda, Iressa, and Portrazza, through our GPI pulse platform as shown in Figure 3.
|Figure 3 – Price Evolution Chart of Opdivo, Keytruda, Portrazza, and Iressa in the United States (Source: GPI Pulse)|
While Opdivo, Keytruda, and Portrazza all have price increments of 1-2%, both Opdivo and Keytruda have more frequent price increases than Portrazza. Portrazza is only indicated as an EGFR-inhibitor while Opdivo and Keytruda have over 10 different indications each. Within the same period, Portrazza has four price increases while Keytruda has eight price increases and Opdivo ten. This is further illustrated by their cumulative price increases, which represents their total price increase since their launch date. Opdivo has had a 14% price increase since its 2014 launch, Keytruda a 13% increase since 2014 and Portazza 8% since 2015. Therefore, we can assume that if a drug is more versatile and can have a more extensive array of indications, while they may not have higher price increases, they may experience these increases more often, which in turn increases profitability. If Capmatinib can become a highly versatile treatment, Novartis can expect to profit significantly from this asset and advance the field of cancer research beyond merely developing a breakthrough therapy.
Utilising our pricing platform GPI pulse to analyse the effect Capmatinib may have in the oncology market if approved, we can conclude that the FDA Priority Approval awarded to this medicine would not only allow for MET-mutated NSCLC to be treated in the near future, but may also change the overall NSCLC drug market due to its possible versatility. If Capmatinib is approved for this specific mutation, Novartis could hold a significant proportion of the market share for this indication for some time. Furthermore, Novartis could also begin to conduct research to expand the medicine’s indications, increasing its versatility and use in other forms of cancer. This would mean that Capmatinib not only has the possibility of becoming a very profitable asset but may also allow for Novartis to find novel ways of treating other forms of cancer, which would significantly increase the value of this medicine.
If you’re interested in learning more about how we went about performing our analysis on pricing evolution and the GPI pulse database we used to derive the data for this analysis then please get in touch below to arrange a call.
Musa Kureshy – Business Development Manager
+44 (0) 203 874 3050
 Cohen, M. H., et al. United States Food and Drug Administration Drug Approval Summary: Gefitinib (ZD1839; Iressa) Tablets. Clinical Cancer Research, 10, 4, 1212–1218, (2004), doi:10.1158/1078-0432.ccr-03-0564