Some posters have discussed Orphan Drug Status as a prospective...

Some posters have discussed Orphan Drug Status as a prospective designation for Vaxinia. I'm not sure that is a pathway to consider as opposed to a Fast Track Approval via the Significant Breakthrough Therapy route, but it is interesting to take a closer look at Orphan Drug Status.

The Orphan Drug Designation

Some notes from my research seem all the more relevant today, than they did way back when…thought I'd share some of my notes from the net here as they could be useful for some readers...

Does Vaxinia pass muster when it comes to orphan drug status? LC recently said “Stay Tuned”. But tuned to what? It’s all food for thought…

Changing market forces

Source : https://www.foley.com/insights/publications/2023/10/strengthening-flow-biotech-sector-m-a-pipeline/

The shifting dynamics of the healthcare market also impact trends in biotechnology M&A. The hunt for orphan drug designation status under FDA guidelines—a status that companies desire because it allows them to claim incentives for drugs and biologics that target rare diseases meeting defined criteria—has created a specialized market that can be highly profitable. Incentives include tax credits for qualified clinical trials, exemptions from user fees, potential for seven-year market exclusivity, and more. As a result, many biotechnology companies seek to acquire or partner with firms skilled in rare disease research and development. These targeted acquisitions enable companies to enter specialized markets and address unmet medical needs more effectively.

Imugene’s Vaxinia Trial is currently treating Bile duct cancer (cholangiocarcinoma), which is rare. About 8,000 people in the United States are diagnosed with it each year. This includes both intrahepatic (inside the liver) and extrahepatic (outside the liver) bile duct cancers. But the actual number of cases is likely to be higher, because these cancers can be hard to diagnose, and some might be misclassified as other types of cancer.

What is the Orphan Drug Act for cancer?

Although there is no universally accepted definition for a rare cancer, the Orphan Drug Act defines a rare disease or condition as one which affects less than 200,000 people in the United States (U.S). The Orphan Drug Act defines a rare disease or condition as one(b) for which there is no reasonable expectation that the cost of developing a drug and making it available in the U.S. will be recovered from sales in the country

How does a drug get orphan drug status?

FDA may grant orphan drug designation to a drug that is otherwise the same drug as a drug already approved in the U.S. for the same rare disease or condition only if the sponsor can present a plausible hypothesis that its drug may be clinically superior to the previously approved drug.

The 10 latest FDA Orphan Drug Designations for cancer treatments

Source https://www.europeanpharmaceuticalreview.com/article/100803/the-10-latest-fda-orphan-drug-designations-for-cancer-treatments/
By Victoria Rees (European Pharmaceutical Review) 25 September 2019

The FDA grants Orphan Drug Designation to treatments for rare diseases in R&D; here are the 10 most recent for oncologic conditions.

1. ALMB-0168³

…the mAb is a first-in-class humanised antibody agonist”

The humanised connexin 43 (Cx43) monoclonal antibody (mAb) received ODD on 18 September. The antibody is produced by AlaMab Therapeutics, Hong Kong and is indicated for osteosarcoma, a type of bone cancer.

According to the company, the mAb is a first-in-class humanised antibody agonist for the hemichannel Cx43 membrane protein. The mechanism of the medication works by activating the Cx43 protein to release cytokines that inhibit tumour growth.

2. HCC-specific biomarker⁴

A drug produced by TCM Biotech International Corporation, Taiwan, to aid in treatment of hepatocellular carcinoma (HCC) was granted ODD on 18 September.

The drug is for use in hepatitis B (HBV)-related HCC as a biomarker for the condition. The marker works using a combination of human and HBC genome to create a particular HBV-human chimera sequence at each infected hepatocyte. An increase of HBV-human chimera DNA in circulation can therefore be used as an HCC-specific biomarker if tumours expand.

According to TCM Biotech, the new platform “could serve as an assistant diagnostic tool to guide the clinicians to determine the intervals of follow-up in high-risk HBV patients or to evaluate residual tumour after curative therapies in HCC patients.”

3. GB1275⁵

The GB1275 medication, produced by GB006 Inc, US, was endorsed with ODD on 11 September. The drug is indicated to treat pancreatic adenocarcinoma.

A current Phase 1 open-label, multicentre trial is studying the treatment as a monotherapy, in combination with an anti-PD1 antibody or in combination with the standard of care. The drug is administered orally twice daily.

The biopharmaceutical company say they are “pursuing product candidates with strong scientific rationale to address indications where there is both a high unmet need and an opportunity to develop best-in-class or first-in-class programmes.”

4. BGJ398⁶

BGJ398 (infigratinib) is a treatment for cholangiocarcinoma, granted with ODD on 11 September. Produced by QED Therapeutics, US, the drug is an orally administered fibroblast growth factor receptor (FGFR) 1-3 tyrosine kinase inhibitor.

According to the pharma company, their investigative therapy is a first-in-class candidate, as their mission is to focus on precision medicine for FGFR-driven cancers and diseases.

5. PBCAR20A⁷

A treatment for mantle cell lymphoma received ODD on 11 September, produced by Precision BioSciences Inc, US.

A Phase I/IIa clinical trial is planned for the fourth quarter of 2019 with initial data expected in 2020.

According to the company, PBCAR20A has demonstrated potent in vivo clearance of CD20+ tumour cells and overall tumour volume reduction.

6. GBR 1342⁸

Glenmark Pharmaceuticals, India received ODD for their GBR 1342 treatment for multiple myeloma on 11 September. A first-in-human, open-label, Phase I trial of GBR 1342 is currently ongoing.

7. Amg BiTE^®9

An Amg BiTE^® (bispecific T cell engager) antibody construct with a half-life extension Fc moiety capable of binding to the neonatal Fc receptor, was granted ODD on 11 September. Amgen Inc, US received the designation for the treatment, indicated for acute myeloid leukaemia (AML).

8. CLS-014¹⁰

On 10 September, CLS Therapeutics Inc, US was granted ODD for their CLS-014 (deoxynucleogen) pancreatic cancer treatment.

According to the company, their drug prevents the metastasis of pancreatic adenocarcinoma and is a first-in-class gene therapy platform technology utilising cell-free DNA (cfDNA). “Receiving ODD marks a major milestone for CLS-014 and an important step forward for our transformative anticancer gene therapy platform… Importantly, we have shown that with our gene therapy approach, we can significantly decrease the primary tumour growth and prevent metastases formation in pancreatic cancer models,” commented Dr George Tetz, MD, co-founder and CEO. An Investigational New Drug (IND) application is expected to be filed by the business in 2021.

9. IBI-376¹¹

The IBI-376 (parsaclisib) treatment in development from Incyte Corporation, US was endorsed with ODD on 10 September. The drug is to treat splenic marginal zone lymphoma.

…their drug may provide an option… where PI3Kδ has developed resistance”

A phosphatidylinositol 3-kinase delta (Pi3kδ) signal inhibitor, the treatment is targeted at malignant B-cell growth, survival and migration.

According to the company, their primary focus is on oncology. They say their drug may provide an option for patients where PI3Kδ has developed resistance to current treatments.

10. CC-93269¹²

Celgene International received ODD for their CC-93269 treatment for multiple myeloma on 28 August.

The drug is an asymmetric immunoglobulin G1 (IgG1)-based, B-cell maturation antigen (BCMA) X CD3 T-cell bispecific mAb. It is currently in an open-label, first-in-human Phase I trial.

The company say that their goal is “to deliver truly innovative and life-changing drugs for our patients.”

Is there M&A interest in Orphan Drugs?

Source : https://www.foley.com/insights/publications/2023/10/strengthening-flow-biotech-sector-m-a-pipeline/

Because the sector faces this impending patent cliff, industry observers predict a surge in M&A and market consolidation.“A significant number of blockbuster drugs are losing their exclusivity in the next five years, and we expect that generic and biosimilar competition will be particularly fierce and intense due to cost-containment pressures,” reports Fitch Solutions. “We expect M&A and market consolidation rates to increase in the short to medium term as pharmaceutical companies turn to acquisitions to maintain a constant revenue stream and protect against the upcoming patent cliff.”

Bile Duct Cancer Statistics

Source : https://www.cancer.org/cancer/types/bile-duct-cancer/detection-diagnosis-staging/survival-by-stage.html

The SEER database tracks 5-year relative survival rates for bile duct cancer in the United States, based on how far the cancer has spread. The SEER database, however, does not group cancers by AJCC TNM stages (stage 1, stage 2, stage 3, etc.). Instead, it groups cancers into localized, regional, and distant stages:

• Localized: There is no sign that the cancer has spread outside of the bile ducts.
• Regional: The cancer has spread outside the bile ducts to nearby structures or lymph nodes.
• Distant: The cancer has spread to distant parts of the body, such as the lungs.

5-year relative survival rates for bile duct cancer

These numbers are based on people diagnosed with cancers of the bile duct between 2012 and 2018. They are divided into intrahepatic and extrahepatic bile duct cancers.

Intrahepatic bile duct cancers (those starting within the liver)

	SEER* stage	5-year relative survival rate
1	Localized	23%
2	Regional	9%
3	Distant	3%
4	All SEER stages combined	9%

Extrahepatic bile duct cancers (those starting outside the liver)

(This includes both perihilar and distal bile duct cancers.)

*SEER= Surveillance, Epidemiology, and End Results

	SEER stage	5-year relative survival rate
1	Localized	18%
2	Regional	18%
3	Distant	2%
4	All SEER stages combined	11%

Understanding the numbers

• These numbers apply only to the stage of the cancer when it is first diagnosed. They do not apply later on if the cancer grows, spreads, or comes back after treatment.
• These numbers don’t take everything into account. Survival rates are grouped based on how far the cancer has spread. But other factors, such as your age and overall health, and how well the cancer responds to treatment, can also affect your outlook.
• People now being diagnosed with bile duct cancer may have a better outlook than these numbers show. Treatments improve over time, and these numbers are based on people who were diagnosed and treated at least five years earlier.

Conclusion

Source : https://www.wsj.com/articles/BL-270B-2004

Amid the mergers-and-acquisitions boom in the pharmaceutical industry, one trend is increasingly discernable – orphan drugs are a desirable target. In fact, half of the recent acquisitions among drug makers and biotechs involved an orphan drug, according to Moody’s Investor Service. Of 18 deals announced since August, nine involved an orphan drug, which is used to treat a rare disease.

The downside with orphan drug status is often the cost of the orphan drugs, given the rareness of the drugs being treated. Eleven orphan drugs with annual costs per US patient of more than $225,000, tends to raise alarm bells, so there is definitely still room for improvement.


DYOR Opinions only