Oncotelic Therapeutics Inc (OTLC)

[PinkOnion]

$OTLC and parkinson disease
DD

Companies, beside Oncotelic (OTLC), currently working on Parkinson Disease include: Astrazeneca (AZN), Roche (RHHBY), Prothena (PRTA), Meiragtx (MGTX), Annovis Bio (ANVS), Horizon Therapeutics (HZNP), Clene Nanomedicine (CLNN), Sage Therapeutics (SAGE), Aptinyx (APTX), Novo Nordisk (NVO), Sanofi (SNY), Anavex Life Sciences (AVXL), Sio Gene Therapies (SIOX), Oxford Biomedica (OXBDF), Sun Pharma Advanced Research (SPARC), UCB (UCBJY), Lilly (LLY).

Background on the Sector

Prevalence:

Nearly one million people in the U.S. are living with Parkinson's disease (PD), which is more than the combined number of people diagnosed with multiple sclerosis, muscular dystrophy and Lou Gehrig's disease (or Amyotrophic Lateral Sclerosis). This is expected to rise to 1.2 million by 2030. Approximately 60,000 Americans are diagnosed with PD each year. More than 10 million people worldwide are living with PD. Incidence of Parkinson’s disease increases with age, but an estimated four percent of people with PD are diagnosed before age 50. Men are 1.5 times more likely to have Parkinson's disease than women. https://www.parkinson.org/Understanding-Parkinsons/Statistics

Health Care cost:

The combined direct and indirect cost of Parkinson’s, including treatment, social security payments and lost income, is estimated to be nearly $52 billion per year in the United States alone. [Yang W, Hamilton JL, Kopil C, Beck JC, Tanner CM, Albin RL, Ray Dorsey E, Dahodwala N, Cintina I, Hogan P, Thompson T (2020) Current and projected future economic burden of Parkinson’s disease in the U.S. npj Parkinson’s Disease 6, 15.].

Treatment Options:

Despite Parkinson’s disease (PD) being the second most common neurodegenerative disease affecting approximately 6 million people worldwide - only symptomatic treatments available that have limited effect as the disease progresses.

On December 21, 2018, the U.S. Food and Drug Administration (FDA) approved Inbrija, an inhaled levodopa powder, for "off" episodes in people with Parkinson's disease treated with levodopa/carbidopa by Acorda Therapeutics (ACOR). The Michael J. Fox Foundation funded early clinical trials of this therapy https://www.businesswire.com/news/home/20181221005620/en/Acorda-Therapeutics-Announces-FDA-Approval-INBRIJA%E2%84%A2-levodopa.

On May 2020, The U.S. Food and Drug Administration has approved Sunovion’s Kynmobi (apomorphine hydrochloride) as an on-demand sublingual treatment for off episodes, or times when medication wears off, in people with Parkinson’s disease. The drug is manufactured by Sunovion. (https://parkinsonsnewstoday.com/2020/05/22/fda-approves-kynmobi-sublingual-film-treat-off-episodes-parkinson/. The medication, formerly known as APL-130277, is an apomorphine film that is placed under-the-tongue (sublingual administration) when patients start experiencing a worsening of their symptoms. It can be taken up to five times a day, at doses ranging from 10 mg to 30 mg.

On April, 2020, Food and Drug Administration (FDA) approved ONGENTYS ® (opicapone), a new medication for treatment of Parkinson’s disease (PD). Opicapone is a catechol-O-methyltransferase (COMT) inhibitor to be used once-daily as an add-on treatment to levodopa for patients who are experiencing OFF time with their current medication regimen. This is manufactured by Neurocrine Bio (NBIX). https://parkinsonsnewstoday.com/2020/04/27/fda-approves-ongentys-add-on-therapy-parkinsons-off-periods-with-levodopa/. Opicapone is in the same class of medications as entacapone and tolcapone which are already approved for use in PD, but it is the first that is available for once-daily use. COMT inhibitors block the breakdown of levodopa in the bloodstream which allows more levodopa to cross into the brain.

Oncotelic

Though visiting the Oncotelic website only disclosed the acquisition of intranasal apomorphine for Parkinson. ED, and FSD. This is expected to be transformative to the company. https://www.oncotelic.com/press-releases/

This is a 505(b)2 strategy. Dr. Trieu – the CEO – and his team has previously developed Abraxane paclitaxel via the 5050(b) strategy over that of an existing paclitaxel on the market- Taxol. Abraxane has since became a billion dollar drug and was acquired by Celgene for 2.9 B. https://www.reuters.com/article/us-abraxis-takeover-celgene/celgene-to-buy-abraxis-bioscience-for-2-9-billion-idUSTRE65T1Z120100630. The acquisition of Abraxis BioScience accelerates Celgene's strategy to become a global leader in oncology. The transaction adds ABRAXANE for Injectable Suspension (paclitaxel protein-bound particles for injectable suspension) (albumin-bound) to the Company's existing portfolio of leading cancer products. Dr. Trieu then went on to develop the next generation Abraxane- Cynviloq at Igdrasol and later on Sorrento Therapeutics (SRNE). This was through the 505(b)2 route also. Cynviloq was acquired by NantPharma for 1.3B. https://www.genengnews.com/news/sorrento-sells-cynviloq-for-1-3b/.

This is a low risk approach to drug development. Drug development is high risk – for every 10 molecules entering clinical trial- only 1 will be survived to regulatory approval. Rather than risking investment dollars on unknown molecule with unknown safety and efficacy, Oncotelic is focusing on Apomorphine which has proven safety and efficacy record in Parkinson and therefore the available 505(b)2 route.

People who are interested in drug development may be aware that New Drug Applications (NDA) and Abbreviated New Drug Applications (ANDA) are 2 of the FDA’s regulatory pathways for how prescription drugs can be approved and ultimately reach the market. In basic terms, NDA’s are for new drugs that have not yet been approved and ANDA’s are for generic products. However, there is an additional pathway that’s a hybrid between the 2 known as 505(b)(2).1

NDA, also called 505 (b)(1), is the format that manufacturers use to bring a formal proposal to the FDA that a new drug should be approved and made available for use by patients in the United States. The NDA includes a great deal of information about the drug being evaluated including the ingredients, how it’s made, pre-clinical (animal model) study results, clinical trial results in humans, what the drug does in the body, and how it will be packaged.2 It takes a great deal of time and resources for a manufacturer to complete all the necessary requirements to submit a successful NDA to the FDA for review.

ANDA is used to gain approval for a generic version of a drug that is already on the market. Earning approval through this pathway involves the manufacturer providing evidence to the FDA that the generic product is comparable to the currently approved product through analytical chemistry and bioequivalence evaluations. The approved indication, dose route, and strength for the generic will be the same as the original (or reference) product. The pathway is abbreviated because preclinical and clinical trials are not required. These studies were performed by the manufacturer of the original product and reviewed by the FDA as part of the approval process, so it would be redundant for the generic manufacturer to complete similar trials again.3 This saves a great deal of time and resources for the manufacturer compared to the NDA.

The 505 (b)(2) pathway provides manufacturers who have certain types of drugs with an opportunity to acquire FDA approval without performing all the work that’s required with an NDA. These drugs are not strictly generics, but are often not entirely novel new molecular entities either. 505 (b)(2) can be an option for drugs with a new aspect related to indication, dosage form or regimen, strength, combination with other products, or other unique traits.1

A key feature of the 505 (b)(2) pathway is that it allows a manufacturer to submit their product for FDA review by including data and/or study results originally collected by another manufacturer or researcher. The manufacturer of the 505 (b)(2) eligible product needs to build a connection between their version of the product, or the active ingredients in it, and the reference product. For example, this could include data and results of bioanalytical testing, pre-clinical studies, or even clinical trial results. If successful in their effort to include supporting evidence from other researchers in their submission, the manufacturer of the 505 (b) (2) candidate won’t have to re-run these studies themselves. While the 505 (b) (2) path allows for using the research of others as a component of their FDA submission, the manufacturer of the 505 (b) (2) product may still need to complete some of their own research in other areas to help fulfill all the various requirements of the FDA to earn approval.4

Another appealing aspect of gaining approval through the 505 (b)(2) is that the approved product is eligible for 3-5 years of market exclusivity. A drug approved via a full NDA is normally granted a 5 year market exclusivity period, while a generic product approved through the ANDA pathway may earn 6 months of market exclusivity if it’s the first generic approved. 5 During the period of market exclusivity the product will be protected from competitors.

The ability to utilize previously completed research as part of the FDA submission can save a great deal of time and money compared to the traditional full NDA. Additionally, a drug being approved through this pathway is not a simple generic of a previously approved product, so it may reach additional patients or perhaps be an improvement over a currently available treatment. Manufacturers have recognized the potential benefits of 505 (b)(2) with 48 drugs gaining FDA approval through the pathway in 2016, a new yearly high since at least prior to 2004. 6505 (b)(2) is expected to continue to be an important pathway for drug development in the future.

https://www.pharmacytimes.com/view/505-b2-regulatory-pathway-for-new-drug-approvals-