March 2022 Drug Launch Highlights

Pluvicto

23 Mar 2022

In possibly groundbreaking news, Novartis announced the FDA approval of Pluvicto (lutetium Lu 177 vipivotide tetraxetan), the first targeted radioligand therapy for progressive, PSMA-positive, metastatic castration-resistant prostate cancer (mCRPC). As part of the VISION trial, Pluvicto demonstrated considerable benefit – with 8.7 months of progression-free survival compared to 3.4 months in the best standard of care arm of the study. Prostate cancer is one of the most commonly diagnosed types of cancer, and is the second leading cause of cancer death in Americans with a prostate gland. The approval heaps competition on POINT Biopharma’s rival targeted radioligand treatment, which is still under investigation. Meanwhile, Pluvicto is also being studied as a first-in-line treatment – in two separate Phase III studies. Pluvicto does face infrastructural challenges for preparation and delivery, with many care centers having no prior experience in handling Lutetium-177; Novartis has prepared a team aiming to expand technical expertise for handling the material, but market size is expected to start out small. The FDA has also approved Locametz, a diagnostic kit using Gallium 68 to identify the expression of PSMA throughout the body and locate metastases which Pluvicto can target – enabling the quick identification of patients who will likely be responsive. Novartis is also working with Lantheus on studies using Pylarify as an imaging-agent for Pluvicto rather than Locametz. The safety profile of Pluvicto is remarkable – with the most common adverse events being fatigue, dry mouth, nausea, anemia, decreased appetite and constipation; relatively benign side effects compared to other cancer treatments. The maximum list price for Pluvicto in the USA will be $255,000 per year.

Keytruda

21 Mar 2022

Pembrolizumab, marketed as Keytruda by Merck, recently picked up another indication with the FDA granting approval for its use in advanced endometrial carcinoma. Keytruda is one of the more successful immune checkpoint inhibitors targeting the Programmed Cell Death Protein 1 (PD-1) receptor. It has only been approved for use in endometrial carcinoma which is microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) who have shown progression despite prior systemic treatments and are not eligible for alternative therapies such as radiotherapy or surgery. The companion diagnostics to determine treatment eligibility through dMMR have also been approved – the VENTANA MMR RxDx Panel; the test to be used to quantify MSI-H was already approved – the Foundation One CDx. In the KEYNOTE-158 trial, 68% of the patient population exhibited response durations of at least 12 months, and 44% of at least 24 months. The recommended dosage is 200mg at 3 week intervals or 400mg at 6 week intervals; this regimen is to be continued until disease progresses, unacceptable toxicity levels or until 24 months. The list price for each 200mg dose of Keytruda is $10,268.72; 400mg doses cost $20,537.44.

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Opdualag

18 Mar 2022

Pharma giant Bristol Myers Squibb received an FDA approval for the use of Opdualag in unresectable metastatic melanoma. Opdualag is a fixed-dose combination of relatlimab, a LAG-3 blocking antibody, and PD-1 targeted antibody nivolumab. Both antibodies are immune checkpoint inhibitors, with relatlimab being the first LAG-3 antibody to receive any regulatory approval. This marks the approval as a milestone – LAG-3 is only the third different immune checkpoint inhibitor target to become commercialized. All other immune checkpoint inhibitor therapies so far have targeted PD-1 and CTLA-4. Samit Hirawat, Chief Medical Officer at Bristol Myers Squibb, highlighted the significance of the event:

“Inhibiting LAG-3 with relatlimab, in a fixed-dose combination with nivolumab, represents a new treatment approach that builds on our legacy of bringing innovative immunotherapy options to patients. The approval of a new medicine that includes our third distinct checkpoint inhibitor marks an important step forward in giving patients more options beyond monotherapy treatment” 

The treatment was investigated in the RELATIVITY-047 trial, which found a statistically significant improvement in progression free survival – 10.6 months in the patient population receiving Opdualag compared to 4.6 months in those only receiving nivolumab. The list price for Opdualag will be $27,389 per infusion, every 4 weeks.

Ztalmy

18 Mar 2022

Marinus Pharmaceuticals, a company focusing on seizure disorder treatment, recently announced the approval of Ztalmy, an oral suspension of ganaxolone. Its approved indication is cyclin-dependent kinase-like 5 (CDKL5) deficiency in patients older than two years old. Ztalmy will be the first treatment approved specifically for CDKL5; the disease causes serious early onset seizures and severe neuro-developmental impairments. This is because the CDKL5 gene codes for a protein that is needed for brain function and development. Ganaxolone positively modulates synaptic and extrasynaptic GABA_A receptors allosterically; this mode of action is responsible for its anti-epileptic and anti-anxiety functions. The Marigold trials conducted by Marinus demonstrated a median 30.7% in 28-day motor seizure frequency, while those treated for 12 months showed a 49.6% reduction. Marinus also has a deal with Orion which gives the rights to Ztalmy in Europe to Orion. The list price for Ztalmy will be $2,425 per bottle, translating to $133,000 per annum.

Adlarity

14 Mar 2022

Corium received the FDA’s approval for its unique Adlarity product to treat Alzheimer’s Disease. Adlarity is a donepezil transdermal system, which delivers the most common treatment for Alzheimer’s-related dementia – donepezil – through a skin patch. Donepezil is a cholinesterase inhibitor and only provides symptom relief for Alzheimer’s, rather than treating the underlying cause of the disease. Adlarity uses Corium’s proprietary CORPLEX technology which enables it to deliver a sufficient dosage of donepezil through a once-weekly patch. The once-weekly administration makes delivery much easier – particularly for dementia patients, but it also comes with safety profile improvements. The current standard of care for donepezil is oral administration, which has been implicated with gastro-intestinal side effects as well as erratic fluctuations in the concentration of the therapeutic in circulation. However, Adlarity is likely to face harsh competition – oral donepezil is now generic, while other cholinesterase inhibitors, such as Rivagtimine, are already available as a transdermal patch. The approval expands Corium’s portfolio in neurology, which is the therapeutic area the company concentrates on, after the approval of AZSTARYS for ADHD in March 2021. Although the approval cements Corium as a serious contender in the CNS field, the disease-modifying agents that are still early in development are expected to shake up the Alzheimer’s space – particularly through combination therapies that include symptomatic relief agents such as Adlarity. Corium will need to stay on top of these developments to maintain an edge over competitors. The approval generated $1.975m in fees for KemPharm, which worked with Corium for the discovery and development of both Azstarys and Adlarity.

Nick Zoukas, Former Editor, PharmaFEATURES